TREATMENT OF DIABETES WITH PANCREATIC ENDOCRINE PRECURSOR CELLS CROSS REFERENCE TO RELATED APPLICATION [0001] The present application is a divisional application of Australian Application No. 2011289379, which is incorporated in its entirety herein by reference. [0001a] The present application claims the benefit of U.S. Provisional Patent Application Serial No. 61/373,109, filed August 12, 2010, which is incorporated herein by reference in its entirety for all purpose. FIELD OF THE INVENTION [0002] The present invention provides a method for lowering blood glucose levels in an animal by transplanting a population of pancreatic endocrine precursor cells into an animal. BACKGROUND [0002a] Any discussion of the prior art throughout the specification should in no way be considered as an admission that such prior art is widely known or forms part of common general knowledge in the field. [0003] Advances in cell-replacement therapy for Type I diabetes mellitus and a shortage of transplantable islets of Langerhans have focused interest on developing sources of insulin-producing cells, or p cells, appropriate for engraftment. One approach is the generation of functional 0 cells from pluripotent stem cells, such as, for example, embryonic stem cells. [0004] In vertebrate embryonic development, a pluripotent cell gives rise to a group of cells comprising three germ layers (ectoderm, mesoderm, and endoderm) in a process known as gastrulation. Tissues such as, for example, thyroid, thymus, pancreas, gut, and liver, will develop from the endoderm, via an intermediate stage. The intermediate stage in this process is the formation of definitive endoderm. Definitive endoderm 1 cells express a number of markers, such as, for example, HNF3 beta, GATA4, MIXL1, CXCR4 and SOX17. [0005] Formation of the pancreas arises from the differentiation of definitive endoderm into pancreatic endoderm. Cells of the pancreatic endoderm express the pancreatic-duodenal homeobox gene, PDX1. In the absence of PDX1, the pancreas fails to develop beyond the formation of ventral and dorsal buds. Thus, PDX1 expression marks a critical step in pancreatic organogenesis. The mature pancreas contains, la among other cell types, exocrine tissue and endocrine tissue. Exacrine and endoerinc issues arisc forn the differentiation of pancreatic endodern. [O06) Ceils bearing the features of islet cells havc reportedly been derved ftoembryonic cells of the mouse r example200i) report differentiation of mouse embryonic stem cels to insulin-secreting structures similar to pancreatic islets. Soria et al Diabetes 49 157 2000) report that insulnvseeting cels deved from mouse embryonic stem cells normalize glycemia in streptozotocin induce diabetic mice, [0097 I one example, H-ior i at (P NAS 99: 16105, 2002disclose that treatment of mouse embryonic stem cells with inhibitors of phosphoinositide 3 knase (iY294002) produced cells that resembled cells 9008 n in another example lyszczuk aPNAS 100:998, 2003) reports the generaion of insulin-producing cells from mouse embryonic stem cells constitutively expressing P %x4, 10009] Micallef etaL reportshat reti noic acid can regulate the commitment of embryonic stem Cells to form PDX I positive pancreatic endodeni Reinoic acid is most detective at inducing PDX t expression when added to cuhures at day fo&rf embryonic stem cell A&crentiaion during a period corresponding to the end of gas'tahion in the embro{Diabetes 54:301 0 [00(1) Miyazaki to reports a mouse embronic stem cell line over-expressing PdxI. Their results show that exogenous Pdx expression clearly enhanced the expression of insulin, sonmatostatin glucokinase, neurogen3, p 4 8 Pax and HNF6 genes in the resulting differentiated cells (Diabetes 53: 1030, 20041. 10010j Skoudy a a. reports that activin A (a member of the TGF- superfamilv)upregulates the expression ofexcrine pancreaic genes (p48 and amylase) and endocrine genes (Pdxl insulin, and glucagon) in mouse embryonic stem cells. The maximal effect was observed using InM activ in A They also observed that the expression level of insulin and Pdx1 mRNA was not affected by retinoic acid; however, 3nM FGF7 treatment resulted in an increased level of the transcript for Pdx , Biochen 379: 749, 2004). 2 [0011 Shiraki al an tJudied the effects of growth factorthat specifically etiance differentiation of embryonic stem cells into PDN I positive cells. Theyv observed that TGF-f2 reproducibly welded a higher proporion of PDX positive cells (Genes Cells 200$ Jn: 10(6 503-16. 100121 Gordon et- a demonstrated the induction of brachxynry [positive]HNF3 beta [positive] endoderr cells from Iouse embryonic stem cells in the absence of seru aand n te presence of activin along with an inhibitor of Wnt signaling (US 20060003446A 1). [00131 Gordon et at (PNAS, Vol 10 1, pae 16806. 2006) states "Wnt and 7GF-beta/ nodal; acttin signalg ae were reqre nan of e anterior primitive streak. 001 41 However, the mouse model of embryonic stem cell developnient may not exactly mimic the developmental program in higher mammals, such as, for example humans. 100151 Thomson , a isolated embryonic stem cells from hnan biastocysts (Science 281 14, 1998 oncurrently, Gehat and coworkers derived human embryonic germ (hEG) cell lines from fetdoadl l tissue (Sharimbktata ProcNati Acad. Sci USA 95:13726, 1998). Unlike mouse embryonic skin cellshich can be prevented from differentiatins simply by culturing with Lkemianahibitory Factor LlF), human embryo K. stm cells must be maintained under very special conditions (L.S Pat No 6.200,206; WO 99/20741; WO 0151616> 100161 DAmour d at describes the production of enriched cultures of human embryonic stem cellderived definitive endoderm in the presence of a high concentation of actlyin and low serurn (Nature Biotechnolog~y 200$ TmnIrasplanting these cells under the kidney capsule of mice resumed in differentiation ino more mature cells with characteristics of some endodernmal organs. Unman embryonic stem cell-derived definitive endoderm cells can be further differentiated into PDX1 positive cells after addition of F10EGEIUS 2005/0266554AI, [00171 DAmour ri at (Nature Biotechnology - 24, 1392 - 1401 (2006)) states "We have developed a differentiation process that converts human embryonic stem hES) cells to endocrine cells capable of synhesizing the pancreatic hormones insulin. giucagon, '3 sonatostatini pancreatic poypeptide and gtrelin, This process miis in in pancreatic~ orangenes is by' directing cells through stages resembling definitive endoderm, gutube endoderm, pancreatic endodem and endocrine precursor en roue to cells that express endocrine hormone ~0018] in another example. 5 Fi et reports. a systemntfor producing pancreatic isilt cells from human embryonic stem cells tU32006/004038SIA1)> in this case, the dfferentiaion pathway was divided into three stages iuman embryonic stem cells were first differentiated to endoderm using a combination of sodium butyr'ate and action A, The cells wereten cultured with TGF-ti antagonists such as Noggin in combination with EGlF or bctacellun to generate PDX1 positive cells. The terminal differentiation was induced by n icotinamide. [00191 in one example, Benvenistry einestates: 'We conchide that overexpression of PDX enhanced expression of pancreatic enriched gene induction of insulin expression may require addi donal signals that are only presetit in -iw' (Benvenistry ew a4 Stem Cells 2006; 2419231930); [00201 in another example. IS2008/0241107 A claims a method for producing a cell that secretes insulin comps i:a) obtaining a cell that does not produce insulin; and. b) incubating the cell with mia containing high glucose, wherein the cell secretes insulin. [00211 Therefore, There still remains a significant need to dcvei coniionsor establishing phripotent olem cell lines that can be expanded to address the current clinical needs, while retaining the potential to d ifferenti ate ito pancreatic endocrine ceils pancreatic hormnu expressing cells, or pancreatic hormone secreting cells. We have taken an alternative approach to improve the efficiency of differentiating human embryonic stem cells toward pancreatic endocrine cells SUMMARY 100221 In one embodiment, the present invention provides a method for lowering blood ghtcose levels in an animal by transplanting a population of pancreatic endocrine precursor cellinto an animalt 4 BRIEF DESCRIPTION OF THE DRAWINGS [00231 Figure 1 shows blood ghucose ee in C Dmice that were rendered diabetic by $ Nations ofstreptozotocin and then transplaned under the kidney capsule with differentiated human ES cellsstage 4) on day Blood glucose tracking of the following several months revealed a graual decline in hyperglycemia to prc-diabetic levels, Subsequent kidney removal rested in a rapid recurrence of diabetes f0024J igg2 shows Human C peptidemeasurenents in plasma samples at the indicated weeks post tansplant show progressive increases commensurate with the fall in blood glucose levels 100251 Figure shows comparable C-epnidelevels are obtained in recipients of cells transplahted under the kidney capsule or subcutaneously within TheraCyte devices, DETAILED DESCRIPTION 100261 For clariy of disclosure and not by way of limitationthe detailed description ofthe invendnon is divided into the folowng subsections that describe or ilustrate certain features embodinlents or applications othe present invention. 00271 Stem cels are undifferentiated cels defined by their ability at the single cell level to both self renew and differentiate to produce progeny cells including sel renewing progenitors nn-renewing progenitorand aly diffeentiated cells Stem cells are also characterized by their ability to differentiate in vitro into funcdonalcells of various cell i neagesfrom multiple germ layers (endodern mesodenn and ectodernt as wel as to ive rise to tissues of muhipie germ layers following transplantation and to contribute substantially to most, if not all, tissues following injetion ino blastocysts. 10028] Stem cell are classified by their developmental potetal as:() totipotent. meaning able to give rise to all embryonic and extmaenbryonic cell types; (2) plurpotent meaning able to give rise to all embryonic cell types; (3) muipotent, meaning able to give ise to a subset of cell lineages but all within a particular tissueorganer physiological system (for exarmpleiematopietic sten cells (HSC) can produce progeny etat include H (sef- a blood e restricted lgotent progeniors and al ceu types and etenents (e.g platelets) that are normal components of the blod); 4) oligopotent meatnig able to gi"e ritse to a mTo restricted subset of cel ineages than mutipotent stem cellsand (5) unipotent, nniaag able to give rise to a single cell lineage (e spermatogelic sten cells. 10029] Differentiation is the process by wich an unspecialized committedte) or less specialized cell acquires the features of a specialized Cell such as, fr example, a nerve cell or a muscle cell A differentiated or diffrentiaion induced cell is one that has taken on a more specialized ( committed) position within the lineage of a cell, The term committeded", when applied to the process of differentiation, reftsto a cel that has proceeded in the differentiation pathway to a point where under normal circumstances it vll continue to differentiate into a specific cell type or subset of cell types. and cannot, under inirmal circumstances. differentiate into a different cell type or revert to a less differentiated cell type De-diftrentiation refers to the process by which a cell reverts to a less specialized (or committed) position within the lineage of a cell As used herein, the lineage of a cell defines the heredity of the cell e whtch cells it care fromnd what celis it can give rise to; The lineage of a cel pices the cell within a hereditary scheme of development and differentiation. A iineag& speci ic marker refers o a characteristic specifically associated with the phenotype of cells of a lineage of interest and can be sed to assess the differentiation of an uncomnrttted cell to the lineage of interest. 100301 "Cells expressing markers characteristic of the defmitnive endoderm lineage" or Stage I cells" or "Stage I as used hr refers to ells expressing at least one of the following markers: SOX-iT ATA4 FfNF3 beta, cSC, CER I, Nodal, FGF8, Bracwhury Mixlike honeobox protein, 17 F 40D48;eomesodcrmin (EOMES) DKK4, FEl M'7 CATA6. CXCR4, -Kit, CD99, or OTX2, Cells expressing markers characteristic of the definitive- endoderm lineage include primitive streak precursor cells, trimniive streak cellsniesendderm cells and defnitive endoderrn cells. f00311 "Cells expressing makers characteristic of the pancreatic endoderr lineage", as used lherein, refers to cells expressing at least one f the following markers: PDXI HNF beta, P alpha MNR, or 1B9. Cells expressing markers chaoateristic of the 6 pancreatc endodern lineage ncide pancreatic en doderm cells, printive gut tube celI, and p'oserior foreat cells, ) [0321 "Cells expreussingirrs characteristic Of the pUncreatic Wndocine lineagO as used herein, refers to cells expressing at least one of the folwin marker NEUROD. ISLI, PDX1I NKX6, I MAFlE insulin. gucagon. or sonatostatn. Cells expressing markers characteristic of the pancreatic endocrine lineage include pancetic endocrine cells, pancreaiuc hormone expressing cells and pancreatic homnone secreting cells, an d cells of the p-ceil lineage 100331 "Definitive endoderm'", as used herein, refers to cells which bearte characteristics of cells arising from the epibiast during gastrulation and which farm the gastrintestinal tract and its derivatives Definitive endodern cells express following markers: HNF3 beta, GATA4, SOX17, Cerberus OTX2, goosecoi<A GKAt. D99 and MIXL [00341 Markers as used herein, are nucleic acid or polypepide molecules that are differentially expressed in a cell of iinerest, In this context. differenti expression means an increased level for a -ositive nmrker amd a decreased level for a negative market. The detectable level of the marker nucleic acid or polypeptide is suffcientl higher or lower in the cells of interest compared to other cells such that the cell of ntcrest can be identified and distinguished from other cells using any of a variety of methods known in the art, [00351 "Pancreatic endocrine cell", or "pancreatic hormone expressing cell as used herin, refers to a cell capable of expressing at least one of the fiowing hormonestinsulini, glucagon somnatostatin.and pancreatic polypeptide. [0031 "'Pancreatic endocrine precursor cell", as used herein refers to a munipotent cell of the definitive endtoderm lineage that expresses NON3 and which can further differentiate into Cells of the endocrine system including . but not limited to, pancreatic islet horrnon-expressing ells Endocrine precursor cells canot differen iate into as many different cell, tissue and/or oran types as compared to less specifically differentiated definitive endoderm lineage cells such as PDXI positive panereatic endoderm cells. .7 [00371 "Pan tic hornnone producing cell' as used herein refers to a cell capable of producing at least one of the following hormow'w insulin. ghigon. somatostnun and pancreatic plpptide. [0038] "Pancreatic hrmone secreting cell" as used herein, refs to a cel capabeof secreting at least one of the flowing hormones: insulin, glucagon. somaostMtin ard pancreatic polypeptide. Isotatin IExpansion and Culture of Pluripotent Stern Cells CharLterizaitoi af Purpot n e Cells f0039] Pluripotent stern cels may expressone or ore of the stagepecific embryonic antigens (SSEA) 3 and 4, and markers detectable uing an tmibodies designatedl'ra-I 60 and Tra. 1I (Thomson er A ,Science 2ii 145. 19981 Differentiation of piripoternt stem cells in Vitr resutd in the ls of SSEA-4 Tra- I 60, and Tra- 1 -S1 expression (if present) and increased expression of SSEA~L I.hldifferetiated puripotent stein ceik typically have alkaline phosphatase activitywhich can be detected by fixing the cells with 4% paraformalidehyde and then developing with Vector Red s a substrate, as described by the manufacturer (Vector Laboratories, Buingame Calit) Undiffereniated pluipotent stem cells also typically express Oct 4 and TERT. as detected by R T-PCR, [00401 Another desirable phenotype of propagated pluripotert stem eels is a potential to differentiate into cells of all three germinal layers: endodermnu tnesodern, and ectoderi tissues Poripotency f pliripotent stem cells can be confirmed for example. by injecting cells into severe combined iintmunodeficient SCID) nice, fixing he terartmas that fArm ning 4% parafonaldehyde and then examining then histologically for evidnce of cel types from t ththree germ layers Alteratively, puripotency may be determined by the creation of embryoid bodies and assessing the embryold bodies for the presence of markers associated with the three germina [0041] Pmpagated pluripotent stem cell lines may be karyotyped using a standard (>bandimg technique amdcompared to published karvotypes of thecr primate species, It is desirable to obtain cells that have a "normal Uaryotype," which means 8 that the cells are euploid,. herein all hunutn chromosomes are present and not noticeeably altered. Sources of P ipotent Stem Cal/ [00421 The types of piripotent stem cells that may be used ie de established lines of phtipotent cells derived from tissue formed after gestation cetding preemhryonic tisue (such as, for example, a blastocyst enbryoie tissue, or fetal tissue taken any during esatio picallyeore approximately 101 2 weeks gestation, Non-limiting examples are established lines of human embryonic stem cells or human embryonic germ cel. such as. for example the human embryonic sten cell lines H 147; and H9 (WiCell. Also contemplated is use of the composidins of this disclosure during the imtiai establishrient or stabilization of such cells in which case te source cells would be primary pluripotent cells taken directly from the source tissues. Also suitable are cells taken from a pluripotent stem cell populatin already culrured in the absencee of feeder cells. Also suitable are mtant human embryonic stem cel lines such affor example B 01v (BresaGen, Athens, GA) {00431 In one embodiment human embryonic sten cell are prepared as described by Thomson a. (US. Pat, No, 5.843,780; Science 282:1145, 1998, Curt Top Dev IoL 38:133 ft. 1998; Proc Nal Acad. Sci, U.S.A; 92:7844 1995), ietare Phelpotent Stemn Ce Hs 100441 In one embodinent, plaripotemn stem cells are typically culured on a layer of feeder cells that support the pluripotent stem cells in various ways Alternatively pluripotent stern cells are cultured ins a culture system that is essentially free of feeder cells but nonethelkss supports proliferation of piunpotent stem cells without undegoing substannad diferemniation. he growth of pluripotent stem cells in fieder-free culture witoutdiferntatin.is supported using a meiu ondhiioned by culturing previously with another cell ty pe Altern atrvely, the growth of piripotenmt stem cells in feeder-free culture without differentiation is supported using a chemically defined meiumn, 9 [00451 For example, Reubinoffit a(Nature Biotechnology 18: 39 - 404 (2000)) and Thompson et a!(Science 6 November 1998 Vol 282 no. 5391 pp. 145 -1147) disclose thecultureof pluripotent stem cel lines from human blastocysts using a mouse embryonic fibroblast feeder cell layer 100461 Richards o, a, (Stem Cells 21: 546556 2003) evaluated a panel of eleven different human adult, fetiand neonatal feeder cell layers for their ability to support human pluripotent stem cell culture.Richards et a states: "human embryonic stem cell lines cultured on adult skin fibroblastfeeders retin human embryonic stem cell motphAlogy and remain pApotent [00471 US20020072117 discloses ceil lines that produce media that support the growth of prime p1luripotent stem cells in feederfree cuflure. The celi lines employed are mesenlhymal and fibroblastike cell lines obtained from embryonic tissue or differentiated from embryonic stem cells U52002007211also discloses the use of the cell ines as a primary feeder cell layer. f004$) In another example Wang a a (Stern Cells 3: 1221-1227, 2005) discloses muethotds for the long-term growth of human puripotent stem cells on feeder cell layers derived from human embryonic stem cells. 100491 Ianoher example, Stojkovic a al (tem Cells 2005 23: 306 314 2005) disclose a feeder ccli systemdeiwd from the spontaneous differentiation of human embryonic ster cells 100501 In a further exampkAywamoto et a? (Stem Cells 22: 433-440, 2004) disclose a source of feeder els obtained from human placenta 100511 Amit a (Biol Replrod 68 215042156, 2003) discloses a feeder cel layer derived. from human foreskin. 10052) In another example lnzunza a a (Stem Cells 23 544-549, 20051dsdose a feeder cell layer fom human postnatal foreskin fibrobiasts. t00531 US56642048 discloses media that support the growth ofprimate plurpotent stem (PS) cels in fAederfree eutre, and cell lines useful for production of such media U1S6642048 states; "This iwention includes mesendtymal and fibrobhat -like cell lines obtained fromt embryonic tissue or dirffereiniated from embryonic stecm cells Methods for deriving such cell lines/processig redia and erowiri stern cells usin te conditioned meoia are described and illustrated in this disclosure 001541 In another example. W020050 14799 discloses conditioned medium frr the maintenance. prolieration and differeniation of mammalian cells. WO 2005014799 states: "The cidture medium produced in accordance with the present invention is conditioted by the cell secretion activity of urie cells; in particular those di ferentiated an immortalized transenic hepaocytes, named MII HN et Murine Hepatocytev" [00551 in another exmple, Xu e. a! (Stem Cels 22; 972-980, 2004) discloses conditioned medium obtained forn human embryonic stem cell derivatives that have been genetically modified to over express b1uman telonerase reverse transcriptase. IP0561 In another exampleU200700 10011 discloses a chemically defined future medium for the maintenance ofphirpotcnt stemn cels. 100571 An altemative culture system employs serumfree medium supplemented with growth factors capable of promoting the pmlferation of embryonic stem cells For example, Cheon elt !(BioReprod DOI: 101 1095/biolreprod105 046870, October 19, 2005) disclose a feede-free serum-free culture system in which embryonic stem cells are maintained in unconditioned serm replacement (gR) iedinm supplemented with different growth factors capable of triggering enbryonic stem cell self-renewa. 1068] In another example, Levenstein etal (Stem ells 24: 568-574, 2006) disclose methods or the long-term culture of human embryonic stem cels in the absence of fibroblasts otecaditioned median, using media supplemented with bFOF. 10059] In another example US20050148070 discloses a method of culturing human embryonic stem cells in defined media without serum and without fibroblast feeder cells. the method comprising: culuring the stem cells in a culue tnedium comtainng albumin amno acds, viamins, minerals at least one transferring or transferrin substnute, at least one insulin or insidin subsitutehe culture medium essentially free of mammalian fetal serum and conaining at least about l00 ng/ml of a fibroblast growth factor capable of activating a fibroblast growth factorsignaling receptor, .11 where the growth factor is supplied from a source other than just a fibroblast feeder layer, the riedirun supported the proliferation of stem cells in an undifftcrentiaed state without feeder cells or conditioned medium [00601 In another example US20050233446 discloses a. defined media usefulinculturing stem cells n u ntiated primate primordial stem cells n solution the m 'eia isooas compared to the stem cells being cultured, in a given culture the particular mediui comprises a base medium and an amout of each of bFGOF insulin, and ascorbic acid necessary to support substantially undifferentiated growth of the primordial stem cells. [0061 in another example; US6800480 states "InL one embodiment, a cell culture medium for growing prnnate-defved primordial sem s ina anay undiiterentiated state is provided which includes a low osmotic pressure, low endotoxi basic medium at is effetive to support the growth of prmate-dcerived primordial stem cells. The basic medium is combined with a nutrient serum effective to support the growth of primate derived prImordmem cells and a substrate selected from the group consistng of feeder ells and an extracelular matrix component derived from (ceder cells The medium fisher inchides non-essential amno acid, an anti-oxidant, and a first growth factor selected frorn the group consisting of iiucleosides and a py'ruvate salt" [00621 in another example; US20050244962 states; "in one aspect the invention provides a method of cuturing prime embryonic stem cellS. One cultures the stem cells in a culte essentially free of mammalian fetal erum (preferably also essentially free of any animal serum) and in the presence of fibroblast growth factor that is suppied from a souce other than just a fibroblast feeder layer. in a preferred ftorn the fibroblast feeder layer, previously required to sustain a stem ce1i culture. is rendered mnecesary by the addition of sufficient fibroblast growth factor" [00631 In a further example. W02005065354 discloses a defied, isotonic cultre medium Ohat is essentially feeder-free and serumwfree, comprisin: a. a basal medium; b. an amount of bFOF sufficient to support growth of substantially undifferentiated mnammlian stemcells; c an amount of insulin sufficient to support growth of substantially undifferentiated mammalian sten cells; and d' an amount of ascorbic .12 acid sufIcielnt tO supnpoft growth of' substantiallyundifferentiated mammnali an stem cells 00641 In anoder eapl.n WO2005086845 discloses a method for maintenance of an differentiated stem cell, said method comprising exposing a stem cell to a member of the tranfonnng goh ofobeta (TG family of proteints a member of the fibroblast grasvih factor (FGP fairly of proteins, or nicotinamide (NIC) in ana-mount suhfcient to maintain the ceU in an undifferentiated state for a sufficient amount of tine to achieve a desired rosut. j00651 The pluripotent stem cels may be plated onto a suitable culture substrate in one embodiment, the suitable culture substrate is an extracelldar matrix component. such as, fr example thos drivd from mnaeent membranle or that may form part of adhesion molecule receptor-li gand couplings, In one embodiment, the sutitabl e culture substrate is MATRI GEL (ecton Dickenson)MARIGELis a soluble preparation from Engelbrelti-olm Swarm tunor cells that gels at room temperature to form a reconsituted basement membrane. t00661 Other extraeelhtar matrix components and component mixtures are suitable as an alternative. Depending on the cell type being proliferated, this may include laminin, fibronectin, proteoglycan, 0mactin heparan sdfate, and the like, alone or in various comb inations. [)067] The impotent stem ells mag be plated onto tie substrate i a stable distribAion and in the presence of a medini that promotes cel survival propagation and retention of the desirable chanxwterstie All these characteristicsbenefit fom careful attennon to the seeding distribution and can readily be determined by one of skill in the art. t00681 Suitable culture media may be made from the follwing components, such as, tor example Dulbecco's modified Eagle's mediu WnDMEM Gibco #f 1965 Knockout Duiheccos modified Eaglemedium NO DMEM Gtbco 10829018; Ham's F1 250% DMEM basal medium; 200 mgM utamines Gibco # 150394027; non essential amino acid sohtion, ibco 11140-50; Amoecaptoethanol, Sigma # uman recombinant basic fibroblast growth factor(bFGF Gibco # 13256 (V19 Formation of Pancreatie Endocrine Precursor Cells [.00691 In one embodiaent; the present invention provides a method for producing pancreatic n ne precior cels hcomprisinig the steps of; a. Cedturing phlipotein stein cels. b. Differendating the plnripotent stenicealls into cells expressing nmarkers characteristic of the definitive endodermn lineage. c. Differentiating the cells expressing markers characteristic of the definitive endoderrm lineage into cells expressing markers characteristic of the pancreatic endoderna an d d, Differendisiing the expressing markers characteristic of the pancreatic endoderm lineage .o pancreatic endocrine precursor cells [00701 luripotent stem cells suitable for usein the present invention include for example, the human embrvunic stem cell line 9 tNi1icode: WA9the human embryonic c stern cell line Hi (,NI1 code. WA), 1 de human embryonic stern cell line H7(NIf code: WA07), and the human embryonic stem celi line SA002(Celartis, Sweden. Also suitable for use in the present inveInion are cells that express at least one of the following markers characteristic of pluripotent cells;ABCC2, CRIPTO, CD9, FOXD3, (mnexin43. Connexin4. OCT4. SOX2, NanoghTERT UTF. ZEP42, SSEA3; SSEA Tra 1-60, Ira 1-81. 10071] Markers characterisne of the definisve endodemni lineage are selected from the group consistng of SOX1? ATA4 HNF3 beta, GS CER Nodal FGF8 Brachyury M ix-ike koneobox protein, FGF4 )CD48, emnesodernin tEOMES), DKK4, FGIF17, GATA6A XCR4, 0Kit, CD9,a X fr in the present invention is a cell that expresses at least one of the makers characteristic of the deiitive endoderm lneage. in one aspect of the present invention, a cell expressing markers charaeistic of the definitive endoderna lineage is a praifive streak precursor cell In an alernate aspect, a Cel expressing markers characteristic of the definitive endoderm lineage is a meseudoderm cell In an alernate aspect a cell expressing 14 markers characteristic of the delniuve endoderm lineage is a defintive endoderm [00721 Markers characteristic of the pancreatic endodermn lineage are :deted folm the gru consibting of PDXI RN FI beta HNF6 RHB and PROX Suitable for use in the present invention is a cell that expresses at least one of the markers characteri:1 ic of the pancreatic endoderm lineage. I one aspect of the present invendont a cell expressing markers charaeterisic of the pancreatic endoder lineage is a pancreatic endoderm cell. [00731 MIarkers characteristic of pancreatic endocrine precursor elsare seated from the group consdstag of NGN3,NKXO.6, NeurD, IS I, PDXI, PAX4rNKX2 or ARX, Suitable for use in the present invennons a cll that expresses at least one of the markers characteristic of pancreatic endocrine prcursor cells. F'rmation Cells Expressing Markers Characteristle f the Dinitie Endaderm Lineage 100741 luripotent stem cells inay be ddlereniiated into Cells expressing markers characterstic of the definitive endoderm lineage by any method in the art or by any method proposed in this invention. t00751 For example, pluripotent stem cells may be differentated into cels expressing markers characteristic of he definitive endodem lneage according to the methods disclosed in I) 'Amour t a Nature Biotechnology 23, 1534-- 1541 (2005) [P0761 For example plurpotentstem cells may be differentiated into cells expressirtg markers characteristic of the deiinitive endodoe.r lineage to the methods disclosed in Shinozaki e a. Development 131, 1651- 1662 (2004) 00771 For example. piuripotent stem cells may be differentiated into ces exprssing markers characteristic of the lefnitive endodern lineage according to the methods disclosed in McLean a l Stem Cells 25 29 - 38 (2007), t0078 For example. purripotentstem cells may be differentiated into cel expressing makers characteristic of the definitive endodemineage according to the methods disclosed in DAmour et Nature Biotechnolocgy 24, 1392 1401 i2006), is [00791 For example. p1 uripotent stem cells may be differentiated into cells expressing miarxers characteristic of the definitive undodern lineage I culturing the pluripotent stem cells in medium containing actvi A in the absence of scramthen culturing the cells with activin A and senum, and then curing the cells with activin A and serum of a different concentration Ar example of this method is disclosed in Nature Bioiechnokogy 2 1534- 1541 (2005) [0080] For example, pluripotent stem cells may be differentiated into cells expressing markers characteristic of the definitive endoderm lineage by culturing the prripotent stem cells in medium containing activin A in the absence of senum, then culturing the cells with activin A with serm of another concentration An example of this method is disclosed in D' Amour et at, Nature Biotechnology 2005. [0081 For example; pluripotent stem cells may be differentiated into cells expressing markers characteristic of the definitive endodermlineage by culuring the piuripotent stem cells in medium containing activin A and a Wnt ligand in the absence of serum. ten removing the Wint ligand and cuhuring thecells with activin A with serum An example of this method is disclosed in Nature Biotechnology 24, 1392 -- 1401 (2006) [00821 For example piuripotent stem cells may be differentiated into cells expressing markers characteristic of the definitive endoderm lineage by treating the plunpotent stem ells according to the methods disclosed in 1S patent application Ser. No, I1 736908, assigned to, ifeScan e inc 100831 For example pluripotent stem cells may be differentiated into cells expressing markers characteristic of the definitive endoderm lineage by treating the pluripotent stem cells according to the methods disclosed in US patentappication Ser No, S1 9 i, assigned to LifeScan, Inc, 100841 For example, pimipotent stem cells may be differentiated into cell expressing markers chaacteristic of the defnitive endoderm lineage by treating the pluripotent stem cells according to the methods disclosed in US patent application Se No 60/990529, [00851 For example; pluripotent stem cells may be differentiated into cells expressing markers characteristic of the definitive endodern lineage by treating the pluripotent 16 stern cells according to the methods disclosed hn US patent appliaNon cr. No 6 U76 889. [0086 For example p1uripotent stem cells may be differentiated into cells pressing markers characteristic of the definitive endoderm limege by trei h p p stem cells according the methods disclosed inS patent application ScNo 6 076.900. [0087 For example. pluripotent stem cells may be differentiated into cells expressing markers characteristic of the definitive endodern lin eage by treating the pluripotent stem cells according to the methods disclosed in US patent application 3cr No. 61/076,908 [0088 For example 1 ripotent stem cells may be differentiated into cells expressing markers characteristic of the deniive endoderm lineage e i tephuripoent stem cells according to the methods disclosed in US patent application 3cro. 61/0%,915. Characteraton of fC/i Exressing MKrscc ter wsic .f tes. toe Endoderm Lineage fQQ89j Formation oc'eells expressing markers caracteristic of the deinitivye endoxderm lineage may be determined by testing r the presence of the markers before and after following a particular protocol. Pluripotent stem cells typrcally do not express such markers. Thus, differentiation of puripotent cells is detected when cells bea to express them. 001901 The efficiency of differentiation may be determined by exposing a treated cell pospuation to an agent (such as an antibody) that specifically recognize'. a protein marker expressed by cells expressing markers characteristic of the defintive end oderm lineage. f009.1 methods for assessing expression of protein and nucleic acizd markers in cultured or noiatcd cells are standard in the art. These inclzidcgnantitatwe reverse transcriptase poiymera se chain reaction ti- PCR\ Norther blots, in siy hybridization (sec. eg, Current Protocols in Molecular Biology (Ausubel et, eds. 2001 supplement)), and 17 inmunoassay such as inofn1histoche mical ny f e material Weern bioti.. and for markershat are accessible in intact ceikfow cytornetry analysis (FACS) (seea g. Hrlow and Iane.Usng Antibodies: A Laboratory Manl New York; Cold Spring Habor Laboratory Press (1998)) 190921 Characteristics of pluripotent stem cells are well known to those skilled in the an, and addittionl characteristics of pluripotent stem cells continue to beidentified Pluripoten stem cell markers include fbr example the e session of one or more of the following:r ABfCO2 CRIP~tO FOXD) C (onnexin43. Concexin45,OCT4, SQXZ. Nanog hTEiRT, UTF I, ZFP42. SSEA-3. SSEA-4 Fra 1-60 Tra 1-81, 1(0931 After treating phuripotent stem cells with the methods of the present inventioithe differenated cells may be purified by expedng a treated cell population to an agent (such as an antibody) that specifically recognizes a protein marker. such as CXCR4 expressed by cells expresun g markers characteristic oAthe define e endoderm lineage, Formation of Cells Expressing Markers Charateristic ofYthe Pancreatic Endoderm Lineage from Lets Expressingy Markers Characteristic of the Definitive Endoderm Lineage 00941 Cell expressing markers characteristicothe define endoderm lineage may be differentiated into cells expressing markers characteristic ol the pancreatic endoderrn lineage by any medod in the art or by any method proposed in this invention, I0951 For example, cells expressing markers characteristic of the definitive endoderm lineage may be differentiated into cells expressing markers characteristic of the pacreatic endoderm lineage according to the methods disclosed in DAmoAer (1 Nature Biotechnology 24 1392- 1401 (2006). 10096j For example, cellsexpressing markers characteristic of the defininve endoderm lineage are further differentied into cells expressing marker characteristic of the pancreatic endoderm lineage, by rating the cells expressing markers characteristic of the definitive endodert lineage with a fibroblast growth factor and the hedgehog signaling pathway inhibior KAAIDcvclopamine, then removing the mediumn containing the fibroblast growh factor and KAAD-cyclopamine and subsequently 18 cdturing the cells in medium containing retnoie acid, a fibrohlast growth factor and KAADeyclopamine. An example of this method is disclosed in Nature iotechnology 24, 1392 401 (2006), 100971 In one aspect fthe preset invention s makers characteristic of the definitive endoderm ineage are further differentiated into cells expressing markers characteristic of the pancreatic endoderm lineage, by treating the cells expressing marke characteristic of the definitive endodermlineage with retinoic acid and at least one fibroblast growth factor A a period of time, according to the methods disclosed in c c S patent application Ser. No, I1 36,90assigned to LifeSan; Ic [00981 In one aspect of the present invetion, cells expressing markers characteristc of the definitive endoderm lineage are farther differentiated into cells expressing markers characteristic of the pancreatic endoderm lineage. by troatingthe cells expressing markers characteristic of the definitive endoderm linege with retinoic acid and at least one fibroblast growth factor for a period of ti-ne at' ding to the methods disclosed in U'S patent application Ser No, 119779311 passed to LifeScan. Inc t00991 in one aspect of the present invention, Cells expressng markers charactersteof the definitive endoderm lineage are further differentiated into cells expressing markers characteristic of the pancreatic endodermlineage by treating the cells expressing iarkers charactedic of the definitive endoder lineage according to the methods disclosed in U2S patent application Ser No:, 990,59 Characterkaian!'CeNs Extorssiqe MarkersC(haraicieeric vf'the Panccrawi Endoderm Lineage 11001 Markers characteristic of the pancreatic endoderm lineage arc well known to those killed in the art and additional markers characteristic of the pancreatic endoderm lineage continue to be identified These markers can he used to confirm that the cells treated in accordance with the present invention have differentiated to acquire the properties characteristic of the pancreatic endoderrn lineage Pancreattc endodern lineage specific markers include the expression of one or more transcription factors such as, for example, H LXB FI I alpha, PDXI 1NF6, HNFI beta. 19 [0 101 The efficiency of differentiation may be deternned by exposing a treated cell population to an agent (such as an antibody) that specifically recognize a protein marker expressed by cells expressing markers characteristic of the pancreatic endoderm lineage. 10102] Methods for assessing express ion of protein and nuclei acid markers in cultured or isolated cells are standard in the art, Theseinclude quantiative reversetranscriptase polmersechan eacionigP~f Nrthern blots, in sit hybridization (see. e gn. Inolvmerase Chain reacuo (I- [(R! hwha Current Protocols in Molecular Biology usubei er a cds 2001 supplement)) and imumossays such as im unOhistocheical analysis of sectined material, Western blottig and for markers that arc accessible in intact cells flow cytometry analysis (FACS) {see. e g. adow and Lane, UsingAntibodies: A Laboratory Manual, New York Cold Spring Harbor Laboratory Press i998)). Formatwn of Pancreaic Endocrine Precursor Clis fromi Cells Expressing Markers Characteristic qf the Pancreatic Endoderm Lineage 10101 in one aspect of the present invention, Cells expressing markers chrnat ristic of the pancreaticendodcerm lineage are differentaed into pancreatic endocrine precursor cels by culturing the cells expressing markers characteristic of the pancreatic endodern lineage in medium supplemented with a actor capable of nhibi ng BMP and a TGFQ receptor 1 ki nase inhibitor. [01041 In one embodiment the factor capable. of inhibiting BMP is noggin. Noggin may be used at a concentration from about 10Opg/ird to about 500tg/nL in one enbodiment noggin is used at a concentration of 100ngml. 101051 in one embodiment the TG-f receptorIkinase inhibitor is ALK5 inhibitor It Calbiochem, Ca), ALKS inhibitor H. n-ay be used at a concentration from about O lpM to about I10pM, in one embodimen L*K5 inhibitor 11 is used at a concentration of pM 0106 In one embodiment the nedinum is DMEM containing 4500mgl glucose and 1% B27. [0107] In one enbodinent the cells are cultured in the culure medium for about tour days. 201 [01081 The efficiency of differentiation may be determined by exposing a treated cell population to an agent (such as an antibody) that specifically recognizes a protein marker expressed by pancreatic endocrine precursor cells [01091 Methods for assessing expression of protein and nuckic acid markers in cultured or isolated cells are standard in the art These inchide quantitative reverse transcriptase polymnerase chain reaction (RT-PCR Northern blots, in sihybridiation (see e g Currentrotocols in Molecular Biology 'A usubel et at, eds, 2001 supplemen) and mmun oassays such as immunohistochemical analysis of sectioned material Western biotung, and for arkerstihat are accessible in intact cells flow cytomnetry analysis (FACS) (see, e.g., Harlow and Lane sing Anibodies: A Laboratory Manual New York: Cold Spring Harbor Laboratory Press (I 99 8 [u116o Characteristics of phiripotent sten cells are well known to those skilled in the art and additional characteristics of puipotent stem cells continue to be identified Pluripotent stem cell markers include ror m the expression of one or more of the fokwing: ABCO2 CRIPTSO NOKD3 Connexin43, Connexin4t, OCT4, SOX2 Nanog WERT, UTFi, ZFP42, SSEA, SSEA -4 Tra 1-60 ra 141. 01111 After treating pnuripotm stem colls with the methods of the present invention, the differentiated cells may be purined by exposing a treated cell population to an agent (such as an antibody that specifically recognizes protein market such as CXCR4, expressed by cells expressing markers characteristic of the pancreatic endoderm lineage. 101121 Markers characteristic of the pancreatic endoderm lineage are selected from the group consisting of PDX1, HNF beta PTFI alpha, HNF6, ilB9 and PROXI Suitable Dr use in the present invention is a cell that expresses at least one of the markers characteristic of the pancreatic endo)derm lineage; Lu one aspect of the present teuon, a cell expresitnmrkers characteristic ol the pancreatic endodermi lineage is a pancreatic endoderm ccliL [01131 Markers characteristic of pancreatic endocrine precursor cells are selected from the group consisting of NONJ. NKX6I NEUROD, ISLI, PDX I PAX4,NKXJL PAX6 or ARX. 21 Formation of Cells Expresslg Markers Characteristie of the Pancreatic Endocrine Lineage from Pancreatic Endocrine Precursor Cells [f01141 i one embodiment, pancreatic endocrine precursor ells produced by the methods of the present invention may be further diffbrertiated into cels expressing markers characteristic of the pancreatic endocrine lineage. 101151 Pancreatic endocrine precursor cells may be diferentiated into cellsexpressing markers charactersstic of the pancreatic endocrine lincege by any, method in the art or by any method proposed in this invention. t0l 61 For example, pancreatic endocrine precursor cells obtained according to the methods of the presot invention are further diterentiated into cells expressing markers characteristic of the pancreatic endorine lineage, by culturing the pancreatic endocrine precursor cells in nediurn conining evendin 4. then removing the medium containing exendin 4 and subsequently cuming the cells in medium containing exendia 1 ,IGFM and HOIF I An example ofhis method is disclosed in DI Amour et a Nature technology 2006, 101171 For example, pancreatic endocrine precursor cells obtained acco rding to the rnt'thods of the presem invention are fuber diferentated into cels expressing markers characteristic of the pancreatic endocri ne lineage, by culturing the pancreatic endctne precursor cells in medium onng DAPT (SigmaAldrih MO) and exendin 4, An example of this medied is disclosed in D- Amour a lNature Biotechnology. 006. 10118 For example, pancreatie endocrine precursor cells obtained according to the. methods of the present inveution are further differentiatetd into cells expressing npmarkers Characteristic of the pancreatic endocrinelineage by cuhuring the pancreatic endocrine precursor cells in medium contains exendin 4. An example of this method is disclosed in DY Amour e d, Nature Biotechnology 2006, 11991 For example, cells pancreatic endocrine precursoar Cells obtained according to the methods of the present invention are further differentiated into cells expressing markers characteristic of the pancreatic endocrine lineage. by trating the pancreatic endocrine precursor cells with a factor that inhibits the Notch signaling pathway, 22 according. to the niethods disclosed in US patent application Ser, No. 111736 908, assigned to LifeScarns hnc [01201 For example pancreatic endocrine precusor cells obtained according toe methods of the present invention are further differentiated into cels express markers characterstic of the pancreatic endocric lineage, by treating the pancreatic endocrine precursor cells with a factor that inhibits the Notch sgmaiing pathway. according to the methods disclosed in US patent application Scr No, Ii 7793 1a sgned to ifUScan, Inc [0211 For example pancreatic endocrine precursor cells obtained according to the methods of the present invention are furTher differentiated into cells expressing markers characteristic o the pancreati endocrine lineage, by treatng the pancreatic endocrine precursor cells with a factorthat inhibits the Notch signaling pathway according to the methods disclosed in US patent application r 1 No 6091537, assigned to LifeScan, lIc 101221 For example, pancreatic endocrine precursor cells obtained according to the methods of the presem invention are further diferentated into cels expressing markers chamteristic of the pancreatic endocrine lineage, by treating the pancreatic endocrine precursor cells with a fctor that inibits the. Nutch signaling pathway according to the methods disclosed i US patent application Ser. No, 60/990,529,assigned to ifeScan, In 101231 Markers characteristic othe pancreatic endocrine lineage are selected from the group consisting ofNEUROD ISLi. PD1, NKX6. 1, PAX4. PAX6, NGN3 ,and NKX2,2, in oni embodiment, a pancreatic endocne cell is capable of expressing at least one of the flowing hormones insulin ghncagotsomatostatin. and pancreatic polypeptide. Suitable for use in the present invention is a cell that expresses at least one of the markers chaacteristic of the pancreatic endocrine lineage. In one aspect of the present invention, a cell expressing markers characteristic of the pancreatic endocrine neage is a pancreatic endocrine cell, The pancreatic endocrine cell may be a pancreatic homoneexpressing cell Altenatively, the pancreatic endocrine cell may be a Pancreatic hormonessecreting cell. 23 [01241 In one aspect of the present invention, the pancreatic endocrine cell is a cell capressing markers characteristic of the P cell lineage A cecl sn markers characteristic of the P ceAi ineage expresses PUI and at least one of the following transenpion factors: NGN- NKX2J, NKX6A I N EUROD, 1SI.. HNF3 beta MAFA PAX4 and PAX$. In one aspect of the present invention, a cell expressing markers characteristic of the 3 cell lineage is a ff cell Therapies 101251 In cne aspect the present iivernion provides a method for treating a patient suffering from, or at risk of developing, Type I diabetes. in one embodimenthe method involves culturing pluripotent cells, differentiatng the pudpotentstem wino into a 0-cell lineage an inpphnting the Cells of a f-cell into a patient Ai an ahernate embodiment the method involves culuring palripotent stem cells, differentiating the piripotent stem clis in vitro into pancreatic endocrine precursor cells, and implanting the pancreatic endodnLe precursor cells into a patient 101261 hi yet another aspect. this invention provides a method fbr treating a patient suffering from or at risk of developing 2 e2 diabetes in one embodiment the method involves culturing pluripotent stem cells, differentiating the piuripoten tem cells in Vtro into a -cdlineae and ipnting the cells of a. ln-geil a patient ii aii alternate embodiment, the method involves culturing phlrpotenit stem ells differentiating the pluripotent stem ells in vino into pancreatic endocrine precursor cellsand implanting the pancreatic endocrine precursor cells into a patient. 10127] If appropriate, the patient can be further treated with piharmaceuical agents or bioactives that facilitate the survival and function of the transplanted cells. These agents may include, for example, insulin, members of the TGF- ly-.z inchiding TOF1 2, and 3, bone morphogenic proteins (MP- 1.T -- 1 -- -7- 1 1 and 1 fibrobiast grow1&cth fetors - and -. 2, liateiet-derived growth factor-AA, and BB plelet ric p m, ilin gr factor (F-, 1II) growth differentiation factor GDF- -6 10, 15 vascular endothelial cell--derived growth factor(VEOF pieiotrophin, endothelin, among others -Other ph armaceu ieal compounds can include, for example, nicotinaIn, glucagon like peptideliOLP-1) andi, 0GLP-1 and 2 mimetibody.xendin -retinoic acidparathyrcd hormone.iARPK inhibitors. 24 such asfor example, copurns disclosed in tiS. Published Apication 2004;209901 and KS. Published Application 2004:0132729, ) [01281 he pluripotent stem cells may be differentiated into an insudinproducing cell prior to transplantation into a recipient. a specific embodiment, the pluripotent stem cells are fully differentiated into P3-elLprior to transplantation into a recipient. Altetnativel the puripotent 'temn cells ny be transplanted into a recipient in an undiferen.tiated or partially differentiated state Further differentiation may take place in the recipient [01291 Definitive endoderm cells or, alteratively, pancreatic endoderm celL or. alternatively. [3 cells. may be implanted as dispersed cells or formed into clusters that may be infused into the hepatie portal vein, Alernatively cells may be provided in biocompatible degradable polymeric supports; porous non-degradable devices or encapsulated to protect from host immune response, Cells may be implated into an appropriate site in a recipient. The implantation sites include, for example, tle liver, natural pancreas, ren subeapsular space. momentum peritonetim, subserosal space., Intestine sonmach, or a ubctaneous pocket [01301 To enhance further differentiation survival or activity of the implanted cells, additional factors, such as Arowth factors, antioxidants or anti AinfnMatory agents can be administered before siutaneouslywith, or after the administration of the cells In certain embodiments gnoth factor re utilized to differentiate the administered cells i viv. These actors can beecreted by endogenums cells and exposed to the administered cellszn situ. implanted cells can be induced to diftferentia te by any combination of endogrenous and exognenouslv administered growth factors known in the art. 1011 The amount of cells used in implantation depends on a nm ber of various factors incIuding the patient condition and response to the theapyand can be deterrinecd by one skilled in the art, j0U32] In one aspect, this invention provides a method for treating a patient suffering from. or at risk of developing diabetes. Thi" method involves culturing pluripotent stem cells, differentiating the cultured cells in vitr into a f-cell lineage, and incorporating the cel into a threedimensional support. The ces can be maintained in vi on this 25 supporprior Jtjipltation into the patient Ahenvdy, the suppotentamtg the cells can be directly implanted in the patient without additional i o cuturing. The support can optionall be incorporated with atleast one phiidactl agent that faci es the surviA and function of the transplanted cells. 101331 Support material\suitable for use for purposes of the present invention include tissue templates, conduits; barries, and reservoirs useful for tissue repair In partitar, synthetic and natural materials in the form of foams, sponges, gels, hdrogels textileN. and nonwoven structures, which have been used in vt and i viv to reconstruct or regenerate biological tissue, as welT as to deliver chemotacic agents for inducing tissue growth are stable for use in practcing the methods of the present nventon See, for example, the materials disclosed in U Patnt S.TW17, U. Patent 6,02Z743, US. Patent 5L67.612 US Patent 5930 US. Patent 6,626,50* U.S. Patent 6534,084,S Patent 6,306,424. L S. Patent 6365. 1 S49 L Patent 6,99 ,323,S. Patent 61656188s U Published Application 20041062753 Al.. S. Patent 42264and U.S. Patent 6,333P29. [01341 To form a support incorporated with a pharmaceutical agent, the pharmaceutical agent can be mixed with the polymer solution pior to forming the support, Alernativel a pharmaceutical agent could be coated on to a fabricated support, preferably in the presence of a pharmaceutical carrier. The pharmaceutical agent nay be present as a liquid, a finely divided solid or any other apopriate physical for. Aternatively excitpiets may be added to the support to alter the release rate of the pharmaceutical agent, in an alternate embodiment, the support is incorporated with at least one pharmaceutical compound that is an anti- inlammatory compound, such as, for example compounds disclosed in U. S, Patent 650, 369. [01351 The support may be incorporated with at least one pharmaceutical compound that is an antiapoptotic compound, such as, for example compounds disclosed in U.S. Patent 6793/945. O01361 The support may alo be incorporated with at least one pharmaceutical compound that is an inhiblior of fibrosis such as, for example compounds disclosed in U.S. Patent 6,33129I 26 [01371 The support may also be incorporatedAith at last one oharmaceutcal compound that is capabe of enhancing aniogenesissuch as. for example compounds disclsed in LS Published Application 2004/022039. and 1.S.Publshed Application 20;-0429901, 101381 The support may a be incorporated with at least one pharmaceutical compound that is an imunosuppressive compound. such as, for example. compounds disclosed in S Published Application 2004,0171623 0139 The support may also be incorporated with at least one pharmaceutical compound that is a growth factor such as for example, members of the T GF-- family, including TGF-I 2.and 3, bone morphogenic proteins (BMR-2, -3,4, -5. -6, 11, -12, and 1 3 fibroblast growth factors- I and -2, platelet-derived growth factor-AA, and -13B platelet rich plasma, insulin growth factor- (I!E-i, 11 growth differentiation factor DF-5 -8, -10 -- 15 vascular endohelialcel-derived growth factor VEGF), pleiotrophin. endothefin, among others, Othcr pharmaceutical compounds can include for example, mncotinide. hypoxia inducible factor 1-alpha, ghuca on ike peptide 1LP 1 GMP-I and UP--2 numetibdy and 11, Exendi-4. nodal, nogn NGF, retinol acid parathyroid hormonetenascin tropoelaslunthrombin-derived peptides, catheicidins defensins. laininn, biological peptides containing cell- and heparin-binding domains of adhesive extracell ular matrix proteins such as fibronectin and vitronectin. tMAPK inhibitors, such as. for example. compounds disclosed in U.S. Published Application 2004/0209901 and - S. Published Application 2004/0132729. 10140j The incorporation of the cells of the- presentinventn into a scafTold can be achieved by the simple depositingof cells onto the scaffold. Cel can enter into the scaffold by simple diffusion (J Pediar. Surg. 23 (1 Pt 2 9( 0 988)) Several other approaches have been developed to enhance the efficiency ofc1 seeding. For example, spnner flasks have becn used in seeding of cihondrocytes onto polyglycolic acid scaffolds (Biotechnol. Prog. 142): 193202 (1 9981> Another approach for seeding cells is the use of centrifugati on wich yields minimum stress to the seeded cells and enhances seeding efficiency For exanpleang et af deveklped a cell seeding method (Jiomed.iater.es 55(3>379-6 (2001)i referred to as Cenrfugationa CeOi immobilizaton (CUT), 27 [01411 The present invention is further illustrated, but not limited by, the following exaraples. REFERENCES f0142j Kamuoen I et al. Incidence of childhood type I diabetes worldwide., Diabetes Mondiale (DiaMond) Project Group.iabetes ar 23, 516-16 (2000) [01431 MathisD, Vence. &: Benoist C Betael death during progression to diabetes. Nare 414,,92--8 (2001), [01441 Ryan, EA t al .inical outcomes and islin secretion aner iet transplantation w it the Edtmonlto pr'otocol Diabete 50. 710 )9(2001(). [01451 Shapiro AM et al. Islet tnsplantation in seen patients with tupe I diabetes mseltu us5 &ing1 a glueocor'ticoid-free imimtunmsuppressive regimesn.ALg! JMed 343. 23(1-8(2000). 101461 Cure P t a improved Metabolic Control and Quality of Lif in Seven Patients With Type 1 Diabetes Following let A fter Kidney Transplanation Tnspiantion 85, 801 812 (2008} 101471 Fung, MA. A a) The effect of medical therapy and islet cell transplantation on diabetic nephropathy; an interim report. Trapiaatti 84, 1 ?22 (2007). [01481 Brown. L, & Edelman, E.R, Optimal control of blood glucose: the diabetic patient or the machine? Ski Tan Ad 2. 27ps 18 (2010), 101491 Guo, T. S Hfebruk N Stemn cells to pancreatic beta-ceils new sources for diabetes cell therapy Endor Rev 30 214? (222009> [01501 Riordi, C. & Edhmd -Toward a rewable sourc of pancreatic beta-cells. Nat BioTechnol6 6,397-8 (2008). 101511 Rajagopal, J, Anderson .. Kame $ Martin 01 & Mlcton, DA. nsulin staining of ES cell pougeny om insulin uptake. Soence 299 363 (2003). 28 [01521 Krouon I et al, Pancreatic endodent deri from human cnryonic stern cells generates glucoseuresponsive instidin-aeered cells in vivo. Nat Biotechn!26. 443~ 52 (20080. 0153) D'mour, KA etal Production of paNcreatic hornTne-eprssmg endocrine cells fron human embryonic stein cell.b Na Boechno/ 24, 1392-401 (2006. 101541 DYAmour, K A. et a Efficient differentiation of human embryonic stn emells to definitive end odera Not Biosechn2 1534-41 (2005). 01551 Natveyenko AV, Georgia S Bhusian A, Butler PC inconsistent formaion and non funcuon of insulin positive cells from pncreatic endoderm derived from human embryonic steim cells in athymie nude rats A P.sin/ Endocrind/ Mea 2010 Jun 29 [Epub ahead of prin], [01561 Lee SIf Hao E, Savino AY Geron It Strongin AY, tkin-Ansai P, Hunan beta-cel precursors mature into functional insulin-producing celsin an imunoisolation device: impl ications fR diabetes cell therapies np/untadn 2a09,19 Apr 15;87(7):983-.91, 101571 Yang Z, Chen N fialkow LB, Ellett i JD Wu R, Nadler JL. Survival of pancreatic islet xenografts in NOD nice with the theracyte device. ansplant Proc 2002 Dec;34(8) 3349-50. [01581 Panepinto LN and Phillips RW TheYucatan miniature pig: characterization and utilization in biomedical research. Lab An/n Ac 36 3434? 186 1591 Larsen MO and Rlin B. se of the Cottingen inipig as a model of diabetes with special focus on type I diabetes research Jar 45; 303 13, 2004, [01601 MilIer ER and Ullrey DE. The pin as a model for hunan nutrition, AntaRev Nutr 7: 36 382 1987 101611 Vodicka P Smetana K, Jr ,Dvorankova B. Emerick T. Xu YZ, Ourednik , Ourednik V.and Motl k IThe. miniature pig as an animal model in biomedical research Ann N Y tad Si 1049 161.- 171, 2005. 29 [0 1621 Krihara 7 Bergsrm T. Wood worth M Feisuln S, and Beal P, haracterization of the Yucatan unmicnur pig skin and sman intestine fir pharmaceutical applications Lab Anim Sc 36; 396-399 - 1986, [0163] Swindle MM. Smith AC. Laber-Laird K, and Dungan L Swine in Biomedica1 Research: Management and Modelsd ar 136: 1-5- 1994. 10164] Bellinger DA, Merricks EP and Nichok TC. Swine moeI of type 2 diabetes mellitus: insulin resiamce, glucose tolerance, and cardiovascular complicationPslar J47 43258 2006. 01651 Hainsworth DP Katz MIL Sanders DA, Sanders [.DN Wright l and Sture M, Retinal capillary basement membrane thickening in a porcine model of diabetes mdellitus. Comp Aed: 52: Y2t2002, [(1661 WarsHaOl KA. Oberhofer iH and Staubesand I. Early micro- and macro-angiopathy in the streptozotocin diabetic mkninp Re Exp Med 4?ed) 177: 58 1980, [01671 Phillips RW, Panepinto M,1> Will DH, and Case OL. The effects of alloxan diabetes on Yucatan miniature swine and their progenya M boism29: 40-- 1980. K01681 Eventov-ridman, Tchoirsh D, Katchman Fl. Shezen E, Aronovich A, eck 0 Dekel B. Rechavi ( 13azar R Feine l, Tal 0, Freud E Reisner Y, Embryonic pig pancreane tissue transplantation &r the treatment of diabetes, PS Md 2006 Ju L3 '. : -2-15 t01691 Castaing %A1 Pault 3 Basmaciogullari A, Casal I Czentiehow P. Schar R.ann K Blood ghucose normizaion upon transplantation of h man embryonic pancreas into beta-celhdefiient 0S1D mice. Dbeilgia 2001 Nov44(1 A)206676, [11 701 Larsen MO Rolii B, Rann K Bjrre Knudsen I, Gotfredsen CF, Bock T, EvuIuation of betacell mass and function in the Otingen ninig, Diabetes ObAietab Suppl 2- A709, 2007 01711 van der Windt Di Echeverri GJ3. Jjzernmans S. Cooper DK The choice of anatomical site fR islet transplantation. Cl ITana 2008:17(9):1005-14, EXAMPLE 34) [01721 Cels of the human embryonitem s cell line H! were cultured on MATRIGEL-coated plates (1:0 dihution. and differeuniated into pancreatic endocrine precursor cells using the folknwingz protocol: a RPMUn medium 'i atu#400 Ivitrogen &a) supplemented with 2% BSA (Catalog# 152401, MP Bionedieal, Ohio) and 100 ng/mI actvin A (R&D Systems dNpus 20 ng/nl WNT-3a (Catalog# 1324-I-WN002 R&D Systems MN) pus no8 ngil of bi F (Catalog# 100>83 Peprofech, NJI or onedy lowed by treatment with Rlmedia supplemented with 2% BSA and 100 ng/ml acdivin A plus ng/mi of bFGF fbr an additional two days (Stage I),then b. DMEM/F TCataoge# 1330, invitrogen, Cay2% BSA + 50 a g/mI EGF7 for three day; (Stage 2), then c. Different basal media indicated in Table I were used, suplemented with in B2 #417504O45 nv itroen A)+ 50 ngmi Ff7+0,25 pM Cyclopainine KAAD (#239804Y Cal bioch(e< m CA) 2 pM Retinoic acid (RA) (Sigma MO) + 100 ng/mI of Noggin CR & D Systems MN for four days (Stage 3) hen A Different basal media indicated in Table I were used, stppkemented with .1% B27 (nvirogen, CA) + 100 ng/mi Nogin + 1 pM4 AIY5ihibitor II (Catalog#f 616452, Calbiochein Ca.) for three days (Stage 4) [61731 Publicatons cited throughout this docunent are hereby incorporated by reference in their entirety. Athough the various aspects of the invention have been illustrated above by reference to.eamplsand prefrred eabodiments, it will be appreciated that the scope of the in on is defined nt bygoing description bt b the fo lowing claims properly construed under principles of patentlaw. 3t