CN105326860A - Application of specific adhesive protein function-blocking mesenchymal stem cell in preparing medicine - Google Patents
Application of specific adhesive protein function-blocking mesenchymal stem cell in preparing medicine Download PDFInfo
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- CN105326860A CN105326860A CN201410314814.2A CN201410314814A CN105326860A CN 105326860 A CN105326860 A CN 105326860A CN 201410314814 A CN201410314814 A CN 201410314814A CN 105326860 A CN105326860 A CN 105326860A
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Abstract
The invention discloses application of a specific adhesive protein function-blocking mesenchymal stem cell in preparing a medicine. The medicine is used for treating ischemic cardia-cerebrovascular diseases. Compared with normal mesenchymal stem cells, the adhesion capacity of the specific adhesive protein function-blocking mesenchymal stem cell disclosed by the invention is significantly reduced, and the number of lung-retaining cells after intravenous injection is greatly decreased, so that the cell quantity of injured cardio-cerebral tissues is significantly increased and damage to a body is relieved. Therefore, the medicine prepared from the specific adhesive protein function-blocking mesenchymal stem cell can be used for effectively treating the ischemic cardia-cerebrovascular diseases, and can be used for significantly reducing lung retaining after intravenous injection; and the medicine is high in utilization rate of drugs, and is good in therapeutic effect and administration safety.
Description
Technical field
The present invention relates to biomedicine field, be specifically related to the purposes of the mescenchymal stem cell of special binding proteins function blocking.More specifically, the mescenchymal stem cell relating to special binding proteins function blocking preparing the purposes in medicine, be used for the treatment of ischemic cardiac, the medicine of cerebrovascular and test kit.
Background technology
Ischemic cardiac, cerebrovascular (cerebral infarction) are the major diseases of serious prestige evil human health, have high incidence, high disability rate and the feature such as high relapse rate, high mortality, bring great psychic pain and financial burden to family and society.Traditional Therapeutic Method effect is undesirable, and survivor leaves serious sequela more.Along with the fast development of stem-cell research, stem cell replacement therapy is expected to for the treatment of the acute heart, cerebral infarction brings breakthrough.Wherein, mescenchymal stem cell (mesenchymalstemcells, MSCs) be a kind of adult stem cell, because it has powerful multiplication capacity and multi-lineage potential, and immunogenicity is low, convenient sources, be easy to separation, cultivate, increase and purification, become the main stem cell kind for treating the acute heart, cerebral infarction, there is development prospect widely.
By intravascular injection mescenchymal stem cell is shipped to site of tissue damage have simple to operate, do not cause the advantages such as new damage, be the desirable route of cellular replacement therapy visceral injury.But research finds, after the mescenchymal stem cell intravascular injection that traditional method is cultivated, angiemphraxis can be caused.After intravenous injection, the cell more than 80% is blocked in Pulmonary Vascular, and cell is very fast dead, makes the cell of the arrival damage heart (or brain) tissue few; And the multiple small infarction of corresponding organ after intra-arterial injection, can be caused, cause new damage.Thus affect effect and the safety of mescenchymal stem cell use.
Summary of the invention
The present invention is intended at least to solve one of technical problem existed in prior art.For this reason, one object of the present invention is that proposing one can be used in treating ischemic cardiac, cerebrovascular, and effectively reduces migrating property of the height mescenchymal stem cell of intravascular injection lung obstruction, and comprises medicine and the test kit of this mescenchymal stem cell.
It should be noted that, the present invention completes based on the following work of inventor:
Anti-adhesion albumen beta 1 antibodies is specificity binding proteins function blocking antibody, can block all containing 12 kinds of binding proteins of β 1 chain and the combination of part, wherein mescenchymal stem cell expresses 7 kinds of binding proteins, is respectively α 1 β 1, α 2 β 1, α 3 β 1, α 4 β 1, α 5 β 1, α 6 β 1, α V β 1.Inventor finds, before intravenous injection mescenchymal stem cell, use anti-adhesion albumen beta 1 antibodies incubated cell, after making mescenchymal stem cell β 1 binding proteins function blocking, significantly can reduce the lung after intravenous injection to be detained, improve the level of mescenchymal stem cell in blood circulation.
Thus, according to an aspect of the present invention, the mescenchymal stem cell that the invention provides special binding proteins function blocking is preparing the purposes in medicine, and described medicine is used for the treatment of ischemic cardiac, cerebrovascular.The discovery that inventor is surprised, relative to the mescenchymal stem cell that common mescenchymal stem cell and special binding proteins function do not block, the mescenchymal stem cell of special binding proteins function blocking of the present invention, its Adhering capacity significantly declines, lung retained cells after intravenous injection significantly reduces, the cell quantity arriving the heart (or brain) tissue of damage obviously increases, and reduces the damage of body.And then the medicine utilizing the mescenchymal stem cell of special binding proteins function blocking to prepare can be effective to treat ischemic cardiac, cerebrovascular, and lung after its intravenous injection is detained and significantly reduces, and utilization ratio of drug is high, therapeutic effect and drug safety good.
According to a further aspect in the invention, present invention also offers one and be used for the treatment of ischemic cardiac, cerebrovascular medicine, described medicine is used for the treatment of ischemic cardiac, cerebrovascular.According to specific embodiment of the invention row, described pharmaceutical pack is containing the mescenchymal stem cell of special binding proteins function blocking.The discovery that inventor is surprised, relative to the mescenchymal stem cell that common mescenchymal stem cell and special binding proteins function do not block, the mescenchymal stem cell of the special binding proteins function blocking comprised in medicine of the present invention, its Adhering capacity significantly declines, lung retained cells after intravenous injection significantly reduces, the cell quantity arriving the heart (or brain) tissue of damage obviously increases, the damage of body is reduced, thus, of the present invention be used for the treatment of ischemic cardiac, cerebrovascular the utilization rate of medicine high, therapeutic effect and drug safety good.
According to another aspect of the invention, present invention also offers a kind of test kit being used for the treatment of ischemic cardiac, cerebrovascular.Arrange according to specific embodiment of the invention, described test kit comprises the mescenchymal stem cell of special binding proteins function blocking, and the mescenchymal stem cell of described special binding proteins function blocking utilizes mescenchymal stem cell described in the function blocking antibody incubation of described special binding proteins to obtain.Inventor finds, relative to the mescenchymal stem cell that common mescenchymal stem cell and special binding proteins function do not block, the mescenchymal stem cell of special binding proteins function blocking of the present invention, its Adhering capacity significantly declines, lung retained cells after intravenous injection significantly reduces, the cell quantity arriving the heart (or brain) tissue of damage obviously increases, and reduces the damage of body.And then, adopt test kit of the present invention, utilize the mescenchymal stem cell of special binding proteins function blocking can effectively treat ischemic cardiac, cerebrovascular, and the lung after this mescenchymal stem cell intravenous injection is detained significantly minimizing, thus utilization rate is high, therapeutic effect and drug safety good.
Additional aspect of the present invention and advantage will part provide in the following description, and part will become obvious from the following description, or be recognized by practice of the present invention.
Accompanying drawing explanation
Above-mentioned and/or additional aspect of the present invention and advantage will become obvious and easy understand from accompanying drawing below combining to the description of embodiment, wherein:
Fig. 1 shows according to one embodiment of the invention, through the fluorescence microscopy result of the matched group of Trypan Blue and the cell of β 1 blocking-up group;
Fig. 2 shows according to one embodiment of the invention, and the lung of the mescenchymal stem cell of the matched group observed under fluorescence microscope and β 1 blocking-up group is detained situation;
Fig. 3 shows according to one embodiment of the invention, the Mean Residence Area comparison figure in lung of the mescenchymal stem cell of matched group and β 1 blocking-up group.
Detailed description of the invention
Embodiments of the invention are described below in detail.Embodiment described below is exemplary, only for explaining the present invention, and can not be interpreted as limitation of the present invention.
According to an aspect of the present invention, the mescenchymal stem cell that the invention provides special binding proteins function blocking is preparing the purposes in medicine, and described medicine is used for the treatment of ischemic cardiac, cerebrovascular.The discovery that inventor is surprised, relative to the mescenchymal stem cell that common mescenchymal stem cell and special binding proteins function do not block, the mescenchymal stem cell of special binding proteins function blocking of the present invention, its Adhering capacity significantly declines, lung retained cells after intravenous injection significantly reduces, the cell quantity arriving the heart (or brain) tissue of damage obviously increases, and reduces the damage of body.And then the medicine utilizing the mescenchymal stem cell of special binding proteins function blocking to prepare can be effective to treat ischemic cardiac, cerebrovascular, and lung after its intravenous injection is detained and significantly reduces, and utilization ratio of drug is high, therapeutic effect and drug safety good.
According to the embodiment of the present invention, the mescenchymal stem cell of described special binding proteins function blocking utilizes mescenchymal stem cell described in the function blocking antibody incubation of described special binding proteins to obtain.Thereby, it is possible to effectively obtain the mescenchymal stem cell of special binding proteins function blocking.
According to the embodiment of the present invention, described special binding proteins is β 1 binding proteins, and the function blocking antibody of described special binding proteins is anti-adhesion albumen beta 1 antibodies.Thereby, it is possible to effectively obtain the mescenchymal stem cell of β 1 binding proteins function blocking.Inventor finds, the mescenchymal stem cell survival ability of this β 1 binding proteins function blocking is constant, Adhering capacity significantly declines, after intravenous injection, lung retained cells significantly reduces, in blood circulation, mescenchymal stem cell level significantly improves, and the cell quantity arriving the heart (or brain) tissue of damage obviously increases.Thus the mescenchymal stem cell of β 1 binding proteins function blocking can be effective to the medicine preparing treatment ischemic cardiac, cerebrovascular.
According to the embodiment of the present invention, under 4 degrees Celsius, described in carrying out, hatch 20-40 minute, preferably 30 minutes.Thus, hatch effective, effectively can block the function of the special binding proteins of mescenchymal stem cell.
According to the embodiment of the present invention, mescenchymal stem cell described in every 1,000,000 adopts 0.1-1.0 μ g, preferably the function blocking antibody of special binding proteins described in 0.5 μ g carry out described in hatch.Thus, hatch effective, effectively can block the function of the special binding proteins of mescenchymal stem cell
According to embodiments of the invention, described medicine passes through vascular drug delivery, preferred intravenously administrable.Thus, therapeutic effect is good.
According to a further aspect in the invention, present invention also offers one and be used for the treatment of ischemic cardiac, cerebrovascular medicine, described medicine is used for the treatment of ischemic cardiac, cerebrovascular.According to specific embodiment of the invention row, described pharmaceutical pack is containing the mescenchymal stem cell of special binding proteins function blocking.The discovery that inventor is surprised, relative to the mescenchymal stem cell that common mescenchymal stem cell and special binding proteins function do not block, the mescenchymal stem cell of the special binding proteins function blocking comprised in medicine of the present invention, its Adhering capacity significantly declines, lung retained cells after intravenous injection significantly reduces, the cell quantity arriving the heart (or brain) tissue of damage obviously increases, the damage of body is reduced, thus, of the present invention be used for the treatment of ischemic cardiac, cerebrovascular the utilization rate of medicine high, therapeutic effect and drug safety good.
According to the embodiment of the present invention, the mescenchymal stem cell of described special binding proteins function blocking utilizes mescenchymal stem cell described in the function blocking antibody incubation of described special binding proteins to obtain.Thereby, it is possible to effectively obtain the mescenchymal stem cell of special binding proteins function blocking, and then be effective to the medicine preparing treatment ischemic cardiac, cerebrovascular.
According to the embodiment of the present invention, described special binding proteins is β 1 binding proteins, and the function blocking antibody of described special binding proteins is anti-adhesion albumen beta 1 antibodies.Thereby, it is possible to effectively obtain the mescenchymal stem cell of β 1 binding proteins function blocking.Inventor finds, the mescenchymal stem cell survival ability of this β 1 binding proteins function blocking is constant, Adhering capacity significantly declines, after intravenous injection, lung retained cells significantly reduces, in blood circulation, mescenchymal stem cell level significantly improves, and the cell quantity arriving the heart (or brain) tissue of damage obviously increases.Thus the mescenchymal stem cell of β 1 binding proteins function blocking can be effective to the medicine preparing treatment ischemic cardiac, cerebrovascular, the medicine of the present invention namely comprising the mescenchymal stem cell of β 1 binding proteins function blocking can be effective to treat ischemic cardiac, cerebrovascular.
According to the embodiment of the present invention, under 4 degrees Celsius, described in carrying out, hatch 20-40 minute, preferably 30 minutes.Thus, hatch effective, effectively can block the function of the special binding proteins of mescenchymal stem cell.
According to the embodiment of the present invention, mescenchymal stem cell described in every 1,000,000 adopts 0.1-1.0 μ g, preferably the function blocking antibody of special binding proteins described in 0.5 μ g carry out described in hatch.Thus, hatch effective, effectively can block the function of the special binding proteins of mescenchymal stem cell.
According to the embodiment of the present invention, described medicine passes through vascular drug delivery, preferred intravenously administrable.
According to the embodiment of the present invention, the dosage of medicine of the present invention is also not particularly limited, in practical operation, doctor can grasp flexibly according to the practical situation of its clinical experience, administration object and disease situation, as long as can obtain good therapeutic effect.According to embodiments of the invention, the dosage of described medicine is: 4000-6000 ten thousand cells/kg, preferably 5,000 ten thousand cells/kg.According to concrete examples more of the present invention, when carrying out zoopery, Babl/c mice body weight being about to 20g enters tail vein injection medicine of the present invention, makes every mice be injected the mescenchymal stem cell of 1,000,000 special binding proteins function blockings.Thus, the cell be detained in mouse lung is few, and in blood circulation, mescenchymal stem cell level is high, and the cell quantity arriving the heart (or brain) tissue of damage is many, thus shows that this dosage can reach good therapeutic effect.
According to another aspect of the invention, present invention also offers a kind of test kit being used for the treatment of ischemic cardiac, cerebrovascular.According to an embodiment of the disclosure, described test kit comprises the mescenchymal stem cell of special binding proteins function blocking, and the mescenchymal stem cell of described special binding proteins function blocking utilizes mescenchymal stem cell described in the function blocking antibody incubation of described special binding proteins to obtain.Inventor finds, relative to the mescenchymal stem cell that common mescenchymal stem cell and special binding proteins function do not block, the mescenchymal stem cell of special binding proteins function blocking of the present invention, its Adhering capacity significantly declines, lung retained cells after intravenous injection significantly reduces, the cell quantity arriving the heart (or brain) tissue of damage obviously increases, and reduces the damage of body.And then, adopt test kit of the present invention, utilize the mescenchymal stem cell of special binding proteins function blocking can effectively treat ischemic cardiac, cerebrovascular, and the lung after this mescenchymal stem cell intravenous injection is detained significantly minimizing, thus utilization rate is high, therapeutic effect and drug safety good.
According to the embodiment of the present invention, the mescenchymal stem cell of described special binding proteins function blocking is the mescenchymal stem cell of binding proteins β 1 function blocking.Thus, when utilizing the test kit treatment ischemic cardiac, the cerebrovascular that comprise the mescenchymal stem cell of this special binding proteins function blocking, because of binding proteins β 1 function blocking of mescenchymal stem cell, thus its Adhering capacity significantly declines, the cell that in therapeutic process, lung is detained significantly reduces, and then the mescenchymal stem cell level in blood circulation effectively improves, the cell quantity arriving the heart (or brain) tissue of damage obviously increases, thus therapeutic effect is better, safety is higher.
Below in conjunction with embodiment, the solution of the present invention is made an explanation.It will be understood to those of skill in the art that the following examples only for illustration of the present invention, and should not be considered as limiting scope of the present invention.Unreceipted concrete technology or condition in embodiment, according to the technology described by the document in this area or condition or carry out according to product description.Agents useful for same or the unreceipted production firm person of instrument, being can by the conventional products of commercial acquisition.
Embodiment 1
Inventor obtains β 1 block mescenchymal stem cell by mescenchymal stem cell and anti-adhesion albumen beta 1 antibodies jointly to be hatched, and demonstrates the survival that anti-adhesion albumen beta 1 antibodies can not affect mescenchymal stem cell, and specific experiment step is as follows:
1, Secondary Culture mescenchymal stem cell is to the 6th generation, peptic cell, the cell precipitation PBS after centrifugal is washed one time, washes away residual cell culture fluid, and 1300rpm discards supernatant after centrifugal 5 minutes.By resuspended for cell precipitation 1%BSA, be 1,000 ten thousand/ml to cell concentration, obtain cell suspension, for subsequent use.
2, test and be set to 3 groups according to antibody adding proportion, be respectively 0.1 μ g β 1 blocking-up group, 0.5 μ g β 1 blocking-up group, 1.0 μ g β 1 blocking-up groups.3 β 1 blocking-up groups add anti-adhesion albumen beta 1 antibodies (cloneP4C10 according to corresponding antibody adding proportion respectively in the cell suspension of its β 1 blocking-up group, Milliporemab1987), then mix, incubated cell, wherein, described in 0.1 μ g β 1 blocking-up group every 1,000,000, mescenchymal stem cell adds 0.1 μ g antibody, described in 0.5 μ g β 1 blocking-up group every 1,000,000, mescenchymal stem cell adds 0.5 μ g antibody, and described in 1.0 μ g β 1 blocking-up groups every 1,000,000, mescenchymal stem cell adds 1.0 μ g antibody.Meanwhile, all establish contrast for each group, each matched group is all that binding proteins β 1 blocking antibody of this group is replaced with the IgG of corresponding dosage as negative control.
Experiment uses corning12 orifice plate.β 1 blocking-up group needs to carry out pretreatment to 12 orifice plates, and step is:
First, adopt 10 μ g/ml fibronectin (FN) to process orifice plate, lower 1 hour of room temperature, sucking-off fibronectin (FN), in superclean bench, blower fan dries up.
Then, close, step is: use 3%BSA (bovine serum albumin) (PBS preparation) bag by orifice plate, and in 37 degrees Celsius, cultivation 1 hour in 5% CO2 gas incubator.
Wherein, matched group, without fibronectin process, only uses the hole of 3%BSA bag quilt as negative control.By the cleaning of 12 orifice plate PBS gentlenesses handled well once, dry up in superclean bench.
3, add 12 orifice plates with the cell suspension of the β 1 blocking-up group after antibody treatment and matched group respectively by step 2, every hole inoculation 50,000 cells, often organize repetition three holes.
4, under 4 DEG C of conditions, by above-mentioned two groups of cell incubation 30 minutes.Then, clean one time with 1mlPBS respectively by through two groups of cells of hatching, and under 1300rpm centrifugal 5 minutes.
5, after utilizing blood counting chamber to carry out cell counting, according to the ratio of 200 μ lPBS/100 ten thousand cells, it is resuspended, for subsequent use respectively two groups of cells through aforementioned processing to be carried out PBS.
6, get 50 μ l cells and carry out Trypan Blue, then in basis of microscopic observation.
Wherein, for 0.5 μ g β 1 blocking-up group and corresponding matched group thereof, through the matched group of Trypan Blue and β 1 blocking-up group cell state as shown in Figure 1, result shows, binding proteins function blocking antibody does not affect the survival of mescenchymal stem cell.
Embodiment 2
By mouse tail vein injection, detect lung that the β 1 obtained in embodiment 1 blocks mescenchymal stem cell and compared with control cells and be detained situation (cell for 0.5 μ g β 1 blocking-up group and corresponding matched group thereof), concrete steps are as follows:
1, zoopery adopts the Babl/c mice in 7-9 week.Often organize 6 mices (body weight is about 20g), the mescenchymal stem cell of binding proteins function blocking embodiment 1 obtained, by tail vein injection in Mice Body, every injected in mice 1,000,000 cell (200 μ l suspension).Injection cell put to death mice after 24 hours, got blood and lung respectively.Cleaned up by lung tissue normal saline, weigh, every mouse gets an identical leaf, leaves and takes frozen section to be done.
2, the tissue of collection 4% paraformaldehyde is fixed 24 hours, then wash three times with PBS, then dewater with the sucrose of 10%, 20%, 30% successively, the sucrose of each concentration dewaters more than 6 hours.Then, after using the freezing embedding medium embedded samples of freezing embedding medium OCT, frozen in-80 DEG C of refrigerators, then, carry out frozen section, the thickness of section is 10 μm.
3, the frozen section of fluorescence microscopy Microscopic observation matched group and β 1 blocking-up group, to determine that the lung of mescenchymal stem cell is detained situation, the results are shown in Figure 2.As shown in Figure 2, compared with matched group, MSC (i.e. mescenchymal stem cell) lung of β 1 blocking-up group (binding proteins function blocking antibody incubation) is detained quantity obviously to be reduced.
4, for the frozen section of matched group and β 1 blocking-up group, ImageJ software is used to carry out quantitative analysis.For the frozen section of each group, 10 visuals field of Stochastic choice every mouse, carry out quantitative analysis, the results are shown in Table 1 and Fig. 3.From the result of table 1 with Fig. 3: compared with the mescenchymal stem cell do not blocked with common mescenchymal stem cell and binding proteins β 1 function, the area quantitative that the mescenchymal stem cell of binding proteins β 1 function blocking is detained in lung significantly reduces.
Table 1
In the description of this description, specific features, structure, material or feature that the description of reference term " embodiment ", " some embodiments ", " example ", " concrete example " or " some examples " etc. means to describe in conjunction with this embodiment or example are contained at least one embodiment of the present invention or example.In this manual, identical embodiment or example are not necessarily referred to the schematic representation of above-mentioned term.And the specific features of description, structure, material or feature can combine in an appropriate manner in any one or more embodiment or example.
Although illustrate and describe embodiments of the invention, those having ordinary skill in the art will appreciate that: can carry out multiple change, amendment, replacement and modification to these embodiments when not departing from principle of the present invention and aim, scope of the present invention is by claim and equivalents thereof.
Claims (10)
1. the mescenchymal stem cell of special binding proteins function blocking is preparing the purposes in medicine, and described medicine is used for the treatment of ischemic cardiac, cerebrovascular.
2. purposes according to claim 1, is characterized in that, the mescenchymal stem cell of described special binding proteins function blocking utilizes mescenchymal stem cell described in the function blocking antibody incubation of described special binding proteins to obtain.
3. purposes according to claim 2, is characterized in that, described special binding proteins is β 1 binding proteins, and the function blocking antibody of described special binding proteins is anti-adhesion albumen beta 1 antibodies,
Optionally, under 4 degrees Celsius, described in carrying out, hatch 20-40 minute, preferably 30 minutes,
Optionally, mescenchymal stem cell described in every 1,000,000 adopts 0.1-1.0 μ g, preferably the function blocking antibody of special binding proteins described in 0.5 μ g carry out described in hatch,
Optionally, described medicine passes through vascular drug delivery, preferred intravenously administrable.
4. be used for the treatment of a medicine for ischemic cardiac, cerebrovascular, it is characterized in that, comprise the mescenchymal stem cell of special binding proteins function blocking.
5. medicine according to claim 4, is characterized in that, the mescenchymal stem cell of described special binding proteins function blocking utilizes mescenchymal stem cell described in the function blocking antibody incubation of described special binding proteins to obtain.
6. medicine according to claim 5, is characterized in that, described special binding proteins is β 1, and the function blocking antibody of described special binding proteins is anti-adhesion albumen beta 1 antibodies.
7. medicine according to claim 5, is characterized in that, under 4 degrees Celsius, hatches 20-40 minute described in carrying out, preferably 30 minutes,
Optionally, mescenchymal stem cell described in every 1,000,000 adopts 0.1-1.0 μ g, preferably the function blocking antibody of special binding proteins described in 0.5 μ g carry out described in hatch.
8. medicine according to claim 5, is characterized in that, the dosage of described medicine is 4000-6000 ten thousand cells/kg, preferably 5,000 ten thousand cells/kg,
Optionally, described medicine passes through vascular drug delivery, preferred intravenously administrable.
9. one kind is used for the treatment of the test kit of ischemic cardiac, cerebrovascular, it is characterized in that, comprise the mescenchymal stem cell of special binding proteins function blocking, the mescenchymal stem cell of described special binding proteins function blocking utilizes mescenchymal stem cell described in the function blocking antibody incubation of described special binding proteins to obtain.
10. test kit according to claim 9, is characterized in that, the mescenchymal stem cell of described special binding proteins function blocking is the mescenchymal stem cell of binding proteins β 1 function blocking.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2011124763A1 (en) * | 2010-04-06 | 2011-10-13 | Suomen Punainen Risti Veripalvelu | Use of a proteolytic enzyme for the modification of the cell surface of a stem cell |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2011124763A1 (en) * | 2010-04-06 | 2011-10-13 | Suomen Punainen Risti Veripalvelu | Use of a proteolytic enzyme for the modification of the cell surface of a stem cell |
Non-Patent Citations (2)
| Title |
|---|
| JAMES E. IP等: "Mesenchymal stem cells use integrin β1 not CXC chemokine receptor 4 for myocardial migration and engraftment", 《MOLECULAR BIOLOGY OF THE CELL》 * |
| 王佃亮等主编: "《细胞移植治疗》", 31 August 2012, 人民军医出版社 * |
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Application publication date: 20160217 |