CN102552880A - Biological preparation for promoting skin wound to be healed - Google Patents
Biological preparation for promoting skin wound to be healed Download PDFInfo
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- CN102552880A CN102552880A CN2011104175904A CN201110417590A CN102552880A CN 102552880 A CN102552880 A CN 102552880A CN 2011104175904 A CN2011104175904 A CN 2011104175904A CN 201110417590 A CN201110417590 A CN 201110417590A CN 102552880 A CN102552880 A CN 102552880A
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Abstract
The invention discloses a biological preparation for promoting a skin wound to be healed. The preparation consists of activin B, mesenchymal stem cells and acceptable pharmaceutic adjuvants. The preparation can well promote the skin wound to be healed.
Description
Technical field
The present invention relates to a kind of biological preparation, particularly a kind of union of wounded skin that promotes contains the biological preparation of stem cell.
Background technology
Along with the raising day by day of The development in society and economy and industrialization degree, the injures and deaths ratio due to wound and other unexpected injuries significantly increases, and has become one of main fatal disease of current society.Skin is the maximum organ of human body, is the barrier that contacts with external environment.The wound healing of skin is the biological process of a complicacy, and it starts incident biology of a series of complicacies, comprises inflammation, organizes new life and reconstructed tissue.
But because skin directly contacts with external environment, skin trauma, particularly large-area skin trauma, its reparation is the comparison difficulty.Common skin wound repair preparation has following several kinds.
1. traditional dressing
Traditional dressing mainly is made up of materials such as cotton, lint, gauzes, is characterized in having good water absorption, thereby can keeps the drying of wound surface.But traditional dressing can not stop wound surface to be infected effectively.And traditional dressing is easy and planing surface sticks together, and makes the wound surface of firm recovery impaired during removal probably once more.Improved oil gauze and antibacterial gauze make traditional artificial skin have anti and antibacterial action.
2. synthesis type dressing
Macromolecule membrane has better elastic and breathability, and common used material has polyurethane, polyethylene, silicone rubber, politef etc.But because its hygroscopicity and water penetration are bad, often cause wound surface place formation hydrops and cause the breeding of antibacterial, so macromolecule membrane is used for epidermis injury more, be not suitable for for large-area skin lesion.Macromolecule sponge body is the tridimensional network thing that macromolecular material forms, and more helps neoblastic formation than thin film, and good permeability, no wound surface adhesion, light weight, characteristics such as comfortable.The high-molecular gel body has good breathability and water penetration, can resist the intrusion of antibacterial, and can be according to the profile of wound surface and molding, and it is bad with attaching property that weak point is to lack ruggedness
3. Biotype artificial skin
Biotype artificial skin is to be taken from natural biological tissue, mainly comprises from body skin, allograft skin and xenogenesis skin.From the body skin is optimal Graftskin in all artificial skins.Application not only can solve the instant needs of large tracts of land skin lesion patient but also can make wound surface return to the outward appearance and the function of normal skin fully from the body skin, is real permanent artificial skin.But exist the source finite sum to influence shortcomings such as attractive in appearance, its use is restricted.Allograft skin is mainly derived from corpse skin.As far back as the forties in last century, alloskin is just as a kind of auxiliary treatment deep burn patient's interim covering.Allogeneic skin have adhesiveness good, can be wound surface advantages such as somatomedin be provided, weak point is possibly propagate infectious diseases such as AIDS, hepatitis, and the allogeneic skin of separate sources has different immunogenicities.
4. organizational project type artificial skin
Organizational project type artificial skin is that recent two decades grows up, and known organization engineering skin has Apligraf, Intergra, Dermagraft etc., the organization engineering skin price and the costliness thereof of these imports.Domestic first also is that the organization engineering skin " peace body skin " of unique State Food and Drug Administration approval is about to listing, also do not bring into use in a large number, and safety is still to be tested with stability.
Along with the development of Tissue Engineering Study, stem-cell research is that repair in trauma provides new approaches.
Mesenchymal stem cells MSCs (Bone mesenchymal stem cells; BMSCs) originate from mesoderm; Have the stronger self renewal and the potential of multidirectional differentiation, can be through the suitable differentiation of inducing to different histiocyte differentiation such as skeletonization, tendon, neurocyte, Skin Cell.In tissue injury's repair process of body, BMSCs migrates to damage location under the distinctive signal effect of damaged tissue, and in local multiplication, and the different damage information of foundation is divided into the different functions sexual cell.The BMSCs at tissue injury position is moved in transplanting, through the repair of two kinds of its tissue injurys of function performance, and the one, under the local microenvironment effect, directed differentiation is the functional cell of particular type, participates in tissue repair directly; The 2nd, through secreting multiple bioactive substance,, improve the regeneration microenvironment of damage location like somatomedin etc., promote tissue repair indirectly.
At present, existing experimental studies results confirms that BMSCs is playing a positive role aspect the promotion wound healing.Badiavas is transplanted to deep with mesenchymal stem cells MSCs (BMSCs), finds the healing that it obviously promotes wound surface, and its effect is better than fibroblast.Pay dogface etc. BMSCs is migrated to the pig deep burn wound, the discovery healing speed is obviously accelerated, and epidermis thickens, and the corium nerve fiber increases, and has improved the wound healing quality greatly.Bibliographical information BMSCs also participates in the reconstruction of epidermis, sweat gland and wound surface blood vessel.These result of study proofs BMSCs is the seed cell of extraordinary skin tissue engineering.
Though BMSCs can well promote wound healing,, be necessary further to improve its repairing effect.
Summary of the invention
The object of the present invention is to provide a kind of biological preparation that can promote union of wounded skin better.
The technical scheme that the present invention taked is:
A kind of biological preparation that promotes union of wounded skin is made up of activin B, bone marrow interstital stem cell and pharmaceutic adjuvant acceptable.
Preferably, the concentration of activin B is 0.5～20ng/ml in the preparation, and the concentration of bone marrow interstital stem cell is 1～8 * 10
6Individual/ml.
The invention has the beneficial effects as follows:
In the preparation of the present invention, there are synergism in activin B and bone marrow interstital stem cell, unite use, can better revise skin wound.
Description of drawings
Fig. 1 is the antigenic expression figure of BMSCs correlating markings thing;
Fig. 2 is the design sketch of the wound healing of different disposal group;
Fig. 3 is the design sketch that BMSCs participates in union of wounded skin;
Fig. 4 is that section is learned by the wound tissue of postoperative different time points;
Fig. 5 is the wound healing process figure of different injection systems;
Fig. 6 is the design sketch that activin B induces the reorganization and the migration of BMSCs actin;
Fig. 7 is the design sketch that activin B induces variation of BMSCs framing structure and cell migration;
Fig. 8 is a Western blot analysis result.
The specific embodiment
A kind of biological preparation that promotes union of wounded skin is made up of activin B, bone marrow interstital stem cell and pharmaceutic adjuvant acceptable.
Preferably, the concentration of activin B is 0.5～20ng/ml in the preparation, and the concentration of bone marrow interstital stem cell is 1～8 * 10
6Individual/ml.
Below in conjunction with embodiment, further specify the present invention.
Below in the experiment, the bone marrow interstital stem cell of use (BMSCs) is taken from tibia and the humerus bone marrow of the animal center SPF of Nanfang Medical Univ level SD rat and is done the former foster gained of being commissioned to train.If no special instructions, ACT refers to activin.
Immunocytochemistry detects BMSCs surface marker antigen presentation
The 3rd generation BMSCs is with 4-5 * 10
5The density in/hole is inoculated in 12 orifice plates, treats that cell grows to 90%, inhales and goes culture medium, and (3 * 5min), 4% paraformaldehyde is 10min fixedly, PBS rinsing (3 * 5min) in the PBS rinsing.0.5%TritonX-100 cell perforation 15min, the PBS rinsing (3 * 5min), and the 1%BSA sealing (RT, 30min); CD44 (rabbit Chinese People's Anti-Japanese Military and Political College Mus, 1:10), CD90 (the mouse anti rat, 1:100) and CD29 (rabbit Chinese People's Anti-Japanese Military and Political College Mus, 1:200); CD80 (rabbit Chinese People's Anti-Japanese Military and Political College Mus, 1:100), 37 ℃ of 2h, PBS rinsing (3 * 5min); Respectively red goat-anti rabbit two anti-(1:200), the anti-mice two of red donkey anti-(1:200) and red goat-anti rabbit two anti-(1:200), RT 1h, PBS rinsing (3 * 5min); Hoechst33258 (1:500) redyes nucleus 10min, and (3 * 5min), mounting is observed in the PBS rinsing.Microscope is taken pictures (Leica DM4000B), chooses 5-7 the visual field under the 20 * times mirror, counting BMSCs surface marker antigen positive expression rate.
The 3rd generation BMSCs is inoculated in 12 orifice plates on the cover glass; When treating that cell grows to 90% fusion; Carry out immunohistochemistry after fixing and detect BMSCs surface marker antigen presentation: red fluorescence dyestuff shows CD29, and CD44 and CD90 positive expression are expressed and CD80 is negative.Hoechst33258 redyes nucleus, and blue-fluorescence shows nucleus.The result is as shown in Figure 1, and as can be seen from the figure, this cell is a mesenchymal stem cells MSCs, and other cells such as non-hematopoietic stem cell.
Continue to cultivate the 3rd generation BMSCs and obtain the 4th generation BMSCs.
Experiment is handled
Trauma model
24 healthy adult SPF level SD rats are divided into four groups at random: the PBS matched group, and the BMSCs transplantation group, Activin B injection groups and Activin B combine the BMSCs transplantation group.10% chloral hydrate (0.003ml/g) intraperitoneal injection of anesthesia, with the depilation of Mel depilation freezing wax, doing area is 1cm after the both sides cropping of SD rat back
2Square cutout reaches subcutaneous deeply.
After wound was made, at the site of injury local injection, injection volume was the 0.4ml/ rat.
Wherein, in the BMSCs transplantation group, the injection concentration of BMSCs is 1 * 10
6BMSCs/ml; In the Activin B injection groups, the injection concentration of Activin B is 5ng/ml; Activin B combines in the BMSCs transplantation group, and the injection concentration of Activin B is that the injection concentration of 5ng/ml, BMSCs is 1 * 10
6BMSCs/ml.
Postoperative animal ad lib, water.Postoperative every day is traced each group wound surface area that do not heal on transparent membrane with thin Mark pen, digital camera under the identical condition to the image photographic tracing under, the IPP image analysis system calculates the wound surface area that do not heal, calculating wound healing rate.Healing rate=(the wound surface area of the healing of original wound surface area-not)/original wound surface area * 100%.
H& E dyeing
Postoperative 3d, 7d, 14d, 21d get wound circumference 0.5cm skin, the PBS flushing, and 4% paraformaldehyde is fixed, the PBS flushing, ethanol dewaters step by step, and xylene is transparent, FFPE.Section (5 μ m), the xylene dewaxing, ethanol is rehydration step by step, conventional hematoxylin Yihong (hematoxylin and eosin, H&E) dyeing.The rat wound healing is carried out histological observation.
Experiment photo such as Fig. 2 and shown in Figure 4, among the figure, Ep refers to epidermis; The D normal skin of making a comment or criticism; G refers to wound place granulation tissue, and scale is 100 μ m.
The result finds to compare with Activin B, BMSCs individual processing group and PBS matched group, and Activin B combines the BMSCs processed group can significantly promote SD rat skin wound healing (Fig. 2 A).After transplanting the 7th day; Activin B combines the wound healing rate of BMSCs processed group to be significantly higher than Activin B, BMSCs individual processing group and PBS matched group (Fig. 2 B); Wound surface to the 14th day is analyzed; Show that Activin B combines the BMSCs processed group can promote the regeneration (14 days H&E of Fig. 2 C postoperative dyeing) of skin follicle, these show that Activin B combines BMSCs can better promote the healing of acute injury.
Experimental result is following:
* the F statistic of main effect and P value; The F statistic of # interaction and P value.
Form the face healing rate to three and carry out the variance analysis of single factor repeated measure, the spherical hypothesis of data fit has significant difference F=674.224 between the postoperative different time, and P < 0.001; PBS group, BMSCs group and ACT B induce the BMSCs group all like this, and the F value is respectively 96.583,397.013 and 473.596, is P < 0.001.The wound healing rate of three different graft groups all in time prolongation and increase, the difference (F=39.993, P < 0.001) of significance is arranged between each group; See from each time point, except postoperative formed in the 3rd day three the face healing rate do not have significant difference (F=0.940, P=0.426) outside, all the other each time points all have the difference (P < 0.001) of significance.There is interaction the postoperative time with transplanting (F=17.985, P < 0.001) between the different grafts.Visible by table 1, the inductive BMSCs of ACT B organizes in postoperative 14d wound healing rate maximum.Three groups of identical time points of postoperative carry out one way analysis of variance, there was no significant difference between three groups of the postoperative 3d; Postoperative 7d, 14dBMSCs form the face healing rate and organize greater than PBS, and ACT B induces BMSCs to form the face healing rate and organizes greater than BMSCs, and significant difference (P < 0.001) is arranged.
The healing that after transplanting, utilized the living imaging appearance to observe the rat skin wound surface on the 3rd, 7 day, there is green fluorescence at the rat skin wound surface place of transplanting the BMSCs of CFSE labelling, and matched group does not have.Further the frozen section result shows, the BMSCs of CFSE labelling has been implanted into the wound surface place, and participates in wound healing.Experimental result is as shown in Figure 3.
H&E dyeing is observed like Fig. 2 C and shown in Figure 4: postoperative 14d, and the equal significance of the healing quality of the inductive BMSCs of ACT is higher than matched group, compares with matched group, and it is fast that the inductive BMSCs of ACT forms the re-epithelialization speed of face, and blood vessel takes place many.Relatively ACT B induces BMSCs group and the evaluation of BMSCs group histopathology, and conclusion shows that the two does not have the difference of significance.But the result shows that the epidermis that the inductive BMSCs of ACT B forms is thicker, and has formed last cornu cutaneum, and this kind structure is not found in the BMSCs group.Significantly the increasing of sweat gland sebaceous gland in the BMSCs group, this phenomenon also is found in ACT B and induces the BMSCs group.
The homologous transplantation approach is not transplanted the influence of the inductive BMSCs of ACT B to wound healing
Adopt different injection systems (epidermis injection, tail vein injection, epidermis injection tail vein injection) to transplant the mixture of ACT B and BMSCs; Wound surface residual area and the wound healing rate of statistics postoperative 3d, 7d, 14d, more the homologous transplantation approach is not to the influence of wound healing.Utilize SPSS 13.0 softwares that two groups of results are carried out the analysis of single factor repeated measure respectively, the result is as shown in the table.
* the F statistic of main effect and P value; The F statistic of # interaction and P value.
* the F statistic of main effect and P value; The F statistic of # interaction and P value.
Three groups of ACT of the different injection systems of different time points induce the process of BMSCs group rat wound healing as shown in Figure 5, figure A: three groups of ACT induce the BMSCs group wound relatively B of area that do not heal: three groups of wound healing rates relatively.
Significant difference F=1078.498 is arranged, P=0.000 between three groups of rat postoperative different time wound surface areas; Epidermis injection groups, tail vein injection group and to close injection groups all like this, F value be respectively 632.86,260.623, and 468.258, be P < 0.001.The wound surface residual area of three different transplantation group all in time prolongation and reduce, but each the group between do not have significance difference (F=2.448, P=0.142); See from each time point, postoperative 7d three form the face residual area have significant difference (F=6.532, P=0.018), in conjunction with transplantation group significantly less than the epidermic grafting group; Postoperative 3d, three transplantation group of 14d do not have significant difference, and the F value is respectively 0.029,0.327, and the P value is respectively 0.972,0.729.The postoperative time and do not have between the homologous transplantation approach interaction (F=0.850, P=0.512).Form the face healing rate to three and carry out the variance analysis of single factor repeated measure, the spherical hypothesis of data fit has significant difference F=959.751 between the postoperative different time, and P < 0.001; Epidermic grafting group, tail vein transplantation group and combination transplantation group are all like this, and the F value is respectively 129.925,447.910 and 535.124, is P < 0.001.The wound healing rate of three different transplantation group all in time prolongation and improve, but each the group between do not have significance difference (F=1.347, P=0.308); See that from each time point postoperative was formed the face healing rate in the 7th day three to be had significant difference (F=5.882 P=0.023), is significantly higher than the epidermic grafting group in conjunction with transplantation group; And postoperative 3d, 14d do not have the difference of significance, and the F value is respectively 0.005 and 0.296, and the P value is respectively 0.995 and 0.751.The postoperative time and do not have between the homologous transplantation approach interaction (F=0.771, P=0.558).
Conclusion
More the inductive BMSCs of homologous transplantation approach ACT B does not organize the influence in wound surface residual area and wound healing rate respectively; The result shows that homologous transplantation approach does not have the difference of significance to wound surface residual area and wound healing rate, and promptly the homologous transplantation approach is not little to the influence of wound healing.But it should be noted that 7d combines transplantation group significantly to reduce than the wound surface residual area of epidermic grafting group after surgery, and the wound healing rate significantly improves, and shows that the homologous transplantation approach possibly not exert an influence to wound healing at specific time point through other mode.
Mechanism of action is analyzed
Transwell cell mobility analysis
The serum-free L-DMEM that adds 300 μ l preheatings in the chamber on the Transwell cell cultivates based on balance 1h in 37 ℃ of incubators.Digestion is centrifugal behind the hungry 12h of the 4th generation BMSCs cell, and serum-free medium is resuspended, and the adjustment cell density is 1 * 10
6/ ml.The last chamber of Transwell adds 100 μ l BMSCs, and following chamber adds the L-DMEM of serum-free or contains 10ng/ml Activin B L-DMEM.Cultivate 24h, take out the Transwell cell, discard culture fluid in the hole, wipe the cell of chamber surface with cotton swab, another side is with the fixing 30min of 4% formaldehyde room temperature.0.1% violet staining 30min, and the distilled water rinsing (3 * 5min), take off the film of Transwell cell, be fixed on the microscope slide, microscopically is observed and is taken pictures (Leica DM4000B), chooses 5-7 the visual field, counting cells number under the 40 * times mirror.
Scratch experiment is analyzed
The 4th generation BMSCs cell grows to 90% back by 4-5 * 10
5The density in/hole is inoculated in 12 orifice plates, and cell grows to 95% and merges, and serum starvation 12h accepts different disposal, moves the liquid head with 10 μ l and marks cut one in each aperture to be measured central authorities, and guarantee that cell comes off fully here.With this moment be 0 point, opening entry cut width.Establish 4 holes for every group, two diverse locations of record in every hole, and use marking pen labelling record position this time.In 12,24,36,48,60,72h in the marking pen present position home position observation cell migration state and gather photo (Leica DMI4000B).
Actin phalloidin (phallotoxins) dyeing
Put into cover glass in 24 orifice plates, the 4th generation BMSCs inoculates wherein, every porocyte content about 1 * 10
4Individual, behind the cultivation 1d, serum starvation 12h.Divide into groups respectively in following time point 30min, 2,4,6 according to different disposal; 12h takes out cover glass, and (3 * 5min), 4% paraformaldehyde is fixed, and PBS cleans (3 * 5min) in the PBS cleaning; 0.1%Tritonx-100 (5min, RT), 1%BSA (20min, RT); Phallotoxins (20min, RT), (3 * 5min), Hoechst33258 (1:500) redyes nucleus 10min in the PBS cleaning; The PBS rinsing (3 * 5min), mounting, microscopically is observed take pictures (Leica DM4000B).
The 4th generation BMSCs, serum starvation 12h, 10ng/ml Activin B handle back 30min; 2h carries out the phallotoxins dyeing of actin, behind the Activin B effect 30min behind 4h and the 6h; The actin fiber mainly is distributed near the cell membrane; During 2h, the actin reorganization generates a large amount of actin fibers and is paved with whole cell and continues to 4h, during effect 6h; A large amount of actin fiber depolymerization partly exist near the cell membrane, and PBS group cell actin fiber number does not change (Fig. 6 A) with distributing.Move the liquid head with 10 μ l and do the BMSCs scratch, in culture medium, adding final concentration then is 10 ng/ml Activin B, and matched group adds the sterilization PBS of equivalent.
72h behind the cut compares with matched group, and Activin B group cell has covered with wound (Fig. 6 B).
Further utilize Transwell to carry out the cell chemotaxis experiment, the last chamber of Transwell adds the DMEM 100 μ l that contain BMSCs, and following chamber adds DMEM culture fluid that contains 10ng/ml Activin B and the DMEM culture fluid that contains equivalent PBS, 37 ℃ of 5%CO respectively
2Cultivate 24h, the result finds to compare with matched group, and cell number is apparently higher than matched group (p on the film of the following chamber of Activin B group<0.05, Fig. 6 C), therefore think that Activin B induces the migration of chemotactic BMSCs.
The above results shows that Activin B induces the chemotactic migration of BMSCs cell and promotes wound healing through the modulate actin reorganization.
The 4th generation BMSCs, behind the serum starvation 12h, divide 5 groups:
The 1st group, add PBS in the DMEM culture medium;
The 2nd group, adding concentration in the DMEM culture medium is 10ng/ml Activin B;
The 3rd group, behind JNK specific inhibitor SP600125 (5 μ mol) processing cell 30min, remove the culture fluid adding and contain 10ng/ml Activin B DMEM culture medium;
The 4th group, behind p38 specific inhibitor SB202190 (5 μ mol) processing cell 30min, remove the culture fluid adding and contain 10ng/ml Activin B DMEM culture medium;
The 5th group, behind ERK specific inhibitor SL327 (5 μ mol) processing cell 30min, remove the culture fluid adding and contain 10ng/ml Activin B DMEM culture medium.
During Activin B effect 2h; Phallotoxins dyeing is observed and respectively organized the discovery of BMSCs actin polymerization: JNK specific inhibitor SP600125 and ERK specific inhibitor SL327 suppress the inductive polymerisation of actin filaments by Activin B significantly; And after p38 specific inhibitor SB202190 handled, Activin B stimulated behind the 2h a large amount of actin polymerizations whole cell (Fig. 7 A) that distributes.Therefore think that Activin B regulates the polymerization of BMSCs actin through JNK and ERK signal path.
After likewise SP600125 and SL327 suppressed JNK and ERK signal, the inductive BMSCs migration of Activin B was suppressed equally, and the BMSCs cell wound surface after 72h only handles through SB202190 after the cell wound has a large amount of cell migration (Fig. 7 B).
Matched group, SP600125 add Activin B group and SL327 and add Activin B and form face less migrating cell is only arranged.
Further utilize Transwell to carry out the cell chemotaxis experiment; After SP600125 and SL327 suppress JNK and ERK signal; The inductive BMSCs chemotaxis of Activin B is suppressed equally, and after SB202190 handles under the inductive BMSCs of Activin B on the film of chamber cell number apparently higher than matched group (p < 0.05).
Western blot analyzes
Cultivate the 4th generation BMSCs, serum starvation 12h removes culture medium in the culture dish, and 37 ℃ of Danks ' wash twice.According to different disposal divide into groups (PBS, ACT B) handle after respectively at following time point 10,30,120min collecting cell total protein; The BCA method is measured protein concentration (Beyotime), and 50 μ g protein electrophoresises (SDS-PAGE) change film (PVDF); Albumen JNK, ERK, p38 are detected in 5% defatted milk powder sealing back; P-JNK, the expression of p-ERK and p-p38, experimental result is as shown in Figure 8.
The above results shows JNK and ERK signal path mediation BMSCs actin polymerization and the migration of Activin B through MAPK family.
Through analysis, can further confirm, with activin B 0.5～20ng/ml, bone marrow interstital stem cell 1～8 * 10 to the mechanism of action between activin B and the BMSCs
6The concentration joint injection of individual/ml also can well promote union of wounded skin.
Claims (2)
1. a biological preparation that promotes union of wounded skin is made up of activin B, bone marrow interstital stem cell and pharmaceutic adjuvant acceptable.
2. the biological preparation of promotion union of wounded skin according to claim 1 is characterized in that: the concentration of activin B is 0.5～20ng/ml in the preparation, and the concentration of bone marrow interstital stem cell is 1～8 * 10
6Individual/ml.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103083721A (en) * | 2013-01-18 | 2013-05-08 | 南方医科大学 | Artificial skin graft for genipin immobilized activin B and preparation method thereof |
| CN115537393A (en) * | 2022-12-05 | 2022-12-30 | 广州优特佳生物科技发展有限公司 | Preparation method and application of umbilical cord mesenchymal stem cell directional secretion group for promoting hair growth |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1456362A (en) * | 2002-05-09 | 2003-11-19 | 中国人民解放军军事医学科学院野战输血研究所 | Artificial skin, preparing method and application thereof |
| CN101008002A (en) * | 2006-01-28 | 2007-08-01 | 肖磊 | Use of Activin A in human embryo stem cell trophoblast-free cell culture |
| CN101451124A (en) * | 2008-12-10 | 2009-06-10 | 戴育成 | Preparation of human umbilical cord mesenchymal stem cells wound surface smearing agent and storage application method |
| EP2243826A2 (en) * | 2004-03-22 | 2010-10-27 | Osiris Therapeutics, Inc. | Mesenchymal stem cells and uses therefor |
| CN102046188A (en) * | 2008-03-27 | 2011-05-04 | 尼奥斯泰姆公司 | Compositions and methods using stem cells in cutaneous wound healing |
-
2011
- 2011-12-14 CN CN2011104175904A patent/CN102552880A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1456362A (en) * | 2002-05-09 | 2003-11-19 | 中国人民解放军军事医学科学院野战输血研究所 | Artificial skin, preparing method and application thereof |
| EP2243826A2 (en) * | 2004-03-22 | 2010-10-27 | Osiris Therapeutics, Inc. | Mesenchymal stem cells and uses therefor |
| CN101008002A (en) * | 2006-01-28 | 2007-08-01 | 肖磊 | Use of Activin A in human embryo stem cell trophoblast-free cell culture |
| CN102046188A (en) * | 2008-03-27 | 2011-05-04 | 尼奥斯泰姆公司 | Compositions and methods using stem cells in cutaneous wound healing |
| CN101451124A (en) * | 2008-12-10 | 2009-06-10 | 戴育成 | Preparation of human umbilical cord mesenchymal stem cells wound surface smearing agent and storage application method |
Non-Patent Citations (4)
| Title |
|---|
| 《解剖学杂志--中国解剖学会2011年年会论文文摘汇编》 20110725 王雪儿、孙丽、陈世萱、张琳 活化素B诱导骨髓间充质干细胞迁移促进大鼠皮肤创面愈合 119 1 , * |
| 《解剖学杂志--中国解剖学会2011年年会论文文摘汇编》 20110725 王雪儿、孙丽、陈世萱、张琳 活化素B诱导骨髓间充质干细胞迁移促进大鼠皮肤创面愈合 119 2 , * |
| 李庆林，肖能坎，张琳: "探讨活化素 B在皮肤创伤愈合中的作用", 《热带医学杂志》, vol. 8, no. 6, 30 June 2008 (2008-06-30), pages 544 - 546 * |
| 王雪儿、孙丽、陈世萱、张琳: "活化素B诱导骨髓间充质干细胞迁移促进大鼠皮肤创面愈合", 《解剖学杂志——中国解剖学会2011年年会论文文摘汇编》, 25 July 2011 (2011-07-25), pages 119 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103083721A (en) * | 2013-01-18 | 2013-05-08 | 南方医科大学 | Artificial skin graft for genipin immobilized activin B and preparation method thereof |
| CN115537393A (en) * | 2022-12-05 | 2022-12-30 | 广州优特佳生物科技发展有限公司 | Preparation method and application of umbilical cord mesenchymal stem cell directional secretion group for promoting hair growth |
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Application publication date: 20120711 |