CN111759865A - Method for promoting umbilical cord stem cell activation and synergistically intervening knee osteoarthritis by using platelet lysate - Google Patents
Method for promoting umbilical cord stem cell activation and synergistically intervening knee osteoarthritis by using platelet lysate Download PDFInfo
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/48—Reproductive organs
- A61K35/51—Umbilical cord; Umbilical cord blood; Umbilical stem cells
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/19—Platelets; Megacaryocytes
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Abstract
A method for promoting the activation of umbilical cord stem cells and cooperatively intervening knee osteoarthritis by using platelet lysate belongs to the technical field of umbilical cord stem cell application. The invention provides application of a platelet lysate in preparing an umbilical cord stem cell adjuvant and application of the platelet lysate in preparing a medicament for treating knee osteoarthritis in cooperation with umbilical cord stem cells. The invention determines the purity and the cytokine content of the platelet lysate, determines the proliferation activity, the cycle progression, the cell cycle related gene expression, the scratch repair capability, the chemotactic migration capability and the chemotactic migration related gene expression of the umbilical cord stem cells, and performs behavioral and histopathological observation tests on rats. The platelet lysate is proved to be suitable for being used as the auxiliary agent of the umbilical cord stem cells, and the mechanism of the platelet lysate acting on the umbilical cord stem cells based on the growth factors and the synergistic application of the platelet lysate in the treatment of knee osteoarthritis are further defined.
Description
Technical Field
The invention belongs to the technical field of umbilical cord stem cell application, and particularly relates to a method for promoting umbilical cord stem cell activation and synergistically intervening knee osteoarthritis by using a platelet lysate.
Background
Mesenchymal Stem Cells (MSCs) have self-renewal capacity, multipotentiality, paracrine effect and immunoregulatory function, can promote the regeneration of damaged tissues, and are important therapeutic tools for cell therapy and regenerative medicine. The sources of mesenchymal stem cells are very wide, such as bone marrow, adipose tissue, menstrual blood and the like. Umbilical cord has long been considered a medical waste, but umbilical cord stem cells (human umbilical cord-derived MSCs, huc-MSCs) have higher plasticity and fewer ethical constraints than stem cells derived from bone marrow and the like, and thus umbilical cord is a very promising source of stem cells. huc-MSCs not only have fast proliferation speed and strong amplification capability, but also have the advantages of no formation of teratoma or tumor, strong immunoregulation capability and the like. More interestingly, huc-MSCs were less immunogenic than other stem cells, making huc-MSCs more suitable candidates for allogeneic transplantation.
Under physiological conditions, platelets activate to release growth factors and play an important role not only in hemostasis, but also in wound healing and tissue regeneration. Platelet Lysate (PL) is obtained after freeze-thaw lysis of platelets. The major factors released from PL include Platelet Derived Growth Factor (PDGF), insulin-like growth factor (IGF), Epidermal Growth Factor (EGF), Fibroblast Growth Factor (FGF), transforming growth factor (TGF- β) and Vascular Endothelial Growth Factor (VEGF). These growth factors can promote cell proliferation, chemotaxis and extracellular matrix production, angiogenesis, etc.
MSCs require a separation and in vitro amplification stage in clinical applications such as cell therapy, tissue engineering, regenerative medicine, etc., to achieve clinically significant cell numbers. In clinical applications based on MSCs cell therapy, there is a major technical hurdle that it is difficult to isolate MSCs from tissues with low levels of MSCs content, and to culture MSCs of sufficient quality and quantity. To achieve successful isolation and rapid expansion of MSCs, the culture medium needs to be supplemented with large amounts of biologically active substances, such as fetal bovine serum. Currently, due to the safety issues associated with immune responses and zoonotic infections using fetal bovine serum, most studies will use serum replacement as a medium supplement or select serum-free medium instead of fetal bovine serum. However, serum replacement or serum-free medium often cannot completely replace the effect of fetal bovine serum, and is expensive and not suitable for large-scale expansion of MSCs. The growth factor-enriched PL has great potential, and can enable MSCs to be amplified in a large scale in the absence of fetal calf serum in one culture period, and meanwhile, the stability of the genome is kept for clinical use. The scientific rationale behind this usage is based on the presence of large amounts of growth factors in platelets that promote stem cell proliferation. However, human blood is generally not a convenient source, even though it is safer than fetal bovine serum. Thus PL is not suitable as a replacement for fetal bovine serum, but still can assist in the culture and application of MSCs.
In the prior art, reports about the amplification culture of umbilical cord stem cells by platelet lysate have been provided, and an animal serum-free and foreign protein-free umbilical cord mesenchymal stem cell culture method is disclosed before, but the technology does not provide a specific cell molecular mechanism related to the proliferation, chemotaxis and regeneration of the platelet lysate to the umbilical cord stem cells, and in addition, in the existing research reports, the auxiliary effect of the platelet lysate to stem cell transplantation treatment is lack of the verification in the aspect of animal experiments. In addition, the platelet lysate and the umbilical cord stem cells are combined to be used for treating knee osteoarthritis, so that the reference basis of the auxiliary effect of the platelet lysate on stem cell transplantation treatment in the aspect of in-vivo animal experiments is provided, and the experimental basis is provided for clinical application of the knee osteoarthritis.
Disclosure of Invention
In view of the above problems in the prior art, it is an object of the present invention to devise a method for providing a platelet lysate to promote the activation of umbilical cord stem cells and to synergistically interfere with osteoarthritis of the knee. The invention proves that the platelet lysate is used as an auxiliary agent for promoting and enhancing umbilical cord stem cells in cell therapy, the platelet lysate is used as an auxiliary supplement for the application of the umbilical cord stem cells, and the platelet lysate and the umbilical cord stem cells are combined to be applied to a cartilage repair action mechanism in the treatment of knee osteoarthritis.
In order to achieve the purpose, the invention adopts the following technical scheme:
use of platelet lysate as an adjunct to cord stem cells in promoting and enhancing cell therapy.
Use of platelet lysates for the proliferation, chemotaxis and regeneration of umbilical cord stem cells based on growth factors.
The use of platelet lysate to improve the viability and biological function of umbilical cord stem cells.
The application of the platelet lysate and umbilical cord stem cells in preparing a medicament for treating knee osteoarthritis.
The application of the platelet lysate and umbilical cord stem cells in preparing cartilage repair medicines for treating knee osteoarthritis.
The invention has the following beneficial effects:
(1) it was verified that platelet lysate is suitable as an adjuvant for umbilical cord stem cells. In addition, the growth factor in the platelet lysate plays an important role in the proliferation, chemotaxis, regeneration, etc. of umbilical cord stem cells.
(2) The mechanism of the platelet lysate acting on the umbilical cord stem cells based on the growth factors and the synergistic application of the platelet lysate in the treatment of knee osteoarthritis are verified, and the viability and the biological function of the umbilical cord stem cells are improved. The active action of the platelet lysate on umbilical cord stem cells is utilized to combine the two so as to achieve the potential of synergistic treatment of knee Osteoarthritis (OA).
Drawings
In FIG. 1, A is a diagram of identifying the purity of human platelet lysate by flow cytometry, B is a diagram of detecting the concentration of growth factor of human platelet lysate by ELISA method, and C is a diagram of determining the influence of human platelet lysate on the activity of umbilical cord stem cells by CCK-8 method;
in FIG. 2, A is a diagram of the results of flow cytometry detection, and B is a diagram of the results of cell cycle-related molecular targets;
FIG. 3 is a graph showing the result of the cell scratch test;
in FIG. 4, A is a graph showing the effect of human platelet lysate on the chemotactic migration of umbilical cord stem cells, and B is a graph showing the effect of human platelet lysate on molecular targets associated with the chemotactic migration of umbilical cord stem cells;
in FIG. 5, A is a graph showing the staining results of safranin-O sections of human platelet lysate, and B is a graph showing the results of mechanical allodynia and thermal pain detection.
Detailed Description
The invention will be further illustrated with reference to specific embodiments and the accompanying drawings.
Given that Platelet Lysates (PL) produce abundant growth factors, PL is assumed to be useful not only in cell culture but also as an adjuvant for promoting and enhancing MSCs in cell therapy. To test this hypothesis, human umbilical cord stem cells were isolated and their effects on MSCs were evaluated at both the cellular and molecular level. Since MSCs have significant efficacy in knee Osteoarthritis (OA), the synergistic effect of PL and MSCs in combination on cartilage damage was further evaluated using a rat OA model, providing evidence for the adjuvant effect of PL in MSCs-based cell therapy. At present, the mechanism of PRP (platelet rich plasma) or PL for the treatment of osteoarthritis has not been elucidated, and the use of PL in combination with MSCs for cartilage regeneration has not been attempted. Therefore, the data of the invention surpass the prior knowledge and provide new information for regenerative medicine, namely PL is used as an auxiliary supplement of the application of MSCs, and the PL is combined with the PL to be used in a cartilage repair action mechanism in OA treatment.
Example 1: preparation of platelet lysate
Collecting peripheral blood with blood collecting tube containing 3.2% anticoagulant (sodium citrate), standing at room temperature for more than 30 min, centrifuging at 210 g for 10 min, collecting upper and middle layers, discarding lower layer plasma, centrifuging at 210 g for 5 min, and removing residual erythrocyte. Then put into a liquid nitrogen or a refrigerator at-80 ℃ for repeated freeze-thaw lysis (3 cycles), or ultrasonic lysis, and a Platelet Lysate (PL) is obtained.
Example 2: determination of the purity of platelet lysates
The PL extracted in example 1 was characterized by flow cytometry, supplemented with 0.9% physiological saline, 10% PL. The result is shown in FIG. 1A, the positive expression rate of CD41A in PL is 99.11%, which indicates that the prepared human platelet lysate PL has high purity.
Example 3: determination of cytokine content in platelet lysate
The content of the cytokine in the PL was measured by ELISA method, and the additives were 0.9% physiological saline and 10% PL. As shown in FIG. 1B, the PDGF content was 26.25. + -. 0.48 ng/ml, TGF-. beta.content was 7.62. + -. 1.29 ng/ml, IFG-1 content was 5.05. + -. 0.15 ng/ml, EGF content was 1.39. + -. 0.08 ng/ml, and FGF content was 0.33. + -. 0.01 ng/ml.
Example 4: determination of proliferation Activity of umbilical cord Stem cells
Detecting the effect of PL and PRP with different concentrations on the activity of umbilical cord stem cells by a CCK-8 method, wherein the additives comprise 10% of fetal calf serum, 0.9% of physiological saline, 0.025% of PL, 0.05% of PL, 0.125% of PL, 0.25% of PL, 0.5% of PL, 1% of PL and 2.5% of PL; 0.025% PRP, 0.05% PRP, 0.125% PRP, 0.25% PRP, 0.5% PRP, 1% PRP, 2.5% PRP. As shown in FIG. 1C, PL at a dilution rate of 1/200 to 1/10 and PRP at a dilution rate of 1/100 to 1/10 both produced significant proliferative effects on umbilical cord stem cells after 24h and 48h of treatment. At 1/50, 1/25, and 1/10 dilution rates, the effect of PL was significant after 24 h; at dilution rates of 1/100, 1/50, 1/25, and 1/10, the effect of PL was significant after 48 h. The effect of PRP was significant after 48h in the case of dilutions 1/50 to 1/10. Indicating that PL has a stronger proliferative effect on umbilical cord stem cells than PRP.
Example 5: determination of cell cycle progression in umbilical cord stem cells
Flow cytometry is adopted to detect the periodic influence of low, medium and high concentration PL and PRP on umbilical cord stem cells, and 10% of fetal calf serum, 0.9% of physiological saline, 0.3125% of PL, 0.625% of PL and 1.25% of PL are added. As shown in FIG. 2A, PL regulates the cell cycle progression of umbilical cord stem cells from G0/G1 to S and G2/M phases. And with increasing PL dose, the percentage of G0/G1 phase gradually decreased, and S phase and G2/M phase gradually increased, compared to the control group. PRP also regulates cell cycle progression, but its effect is much less than high concentrations of PL. Indicating that PL can regulate the progression of the stem cell cycle and is dose dependent.
Example 6: determination of expression of genes associated with cell cycle of umbilical cord stem cells
The influence of PL on mRNA expression of genes related to the cell cycle of the umbilical cord stem cells is detected by adopting a Real Time PCR method, and 10% of fetal calf serum, 0.9% of physiological saline and 1.25% of PL are added. As shown in FIG. 2B, the expression of CDC25A, CCNA2, CCNB1, CCND1, CDK2, E2F1 and E2F2 genes (all of which are significantly upregulated in cord stem cells by high concentrations of PL (all of which are shown in FIG. 2B)P<0.01), down-regulating the expression of the P15 and P16 genes in the umbilical cord stem cells. Indicating that PL can promote the expression of stem cell cycle related molecule target genes.
Example 7: determination of umbilical cord stem cell scratch repair capacity
The influence of PL on migration ability of umbilical cord stem cells was evaluated by cell scratch assay on PL extracted in example 1, which was supplemented with 10% fetal bovine serum, 0.9% physiological saline, 0.3125% PL, 0.625% PL, and 1.25% PL. Results as shown in fig. 3, the ratio of wound area of PL treated 24h, 36h and 48h to untreated (0 h) wound area significantly decreased with increasing PL concentration compared to normal levels: (P<0.01). Indicating that PL promotes wound healing by enhancing the migration capacity of umbilical cord stem cells in a dose-dependent manner. Even after 72h, high concentration PL achieved wound healing. Indicating that PL can promote the repair of cord stem cell scratch.
Example 8: determination of chemotactic migration Capacity of umbilical cord Stem cells
The influence of PL on the chemotactic migration ability of umbilical cord stem cells was evaluated by Transwell assay on PL extracted in example 1 by adding 10% fetal bovine serum, 0.9% physiological saline, 0.3125% PL, 0.625% PL and 1.25% PL. As a result, as shown in FIG. 4A, the number of umbilical cord stem cells migrating to the lower chamber significantly increased with the increase in PL concentration as compared with the normal level (each of which is shown in FIG. 4A)P<0.01) indicating migration of PL to umbilical cord stem cellsTransplantation has a dose-dependent promoting effect. The difference between the number of migration cells of the cord stem cells treated by PRP and the number of migration cells at normal level is not statistically significant. The results indicate that PL increases the chemotactic migratory capacity of umbilical cord stem cells compared to PRP.
Example 9: determination of expression of genes related to chemotactic migration of umbilical cord stem cells
The influence of PL on mRNA expression of related genes of the umbilical cord stem cells is detected by adopting a Real Time PCR method, and 10% of fetal calf serum, 0.9% of normal saline and 1.25% of PL are added. The results are shown in FIG. 4B, and the expression of MMP2, FIBRONOCTIN, VEGF-A, VEGF-C, VIMENTIN, TWIST1 genes in umbilical cord stem cells was significantly up-regulated by the medium concentration PL (all of which areP<0.01). Indicating that PL can promote expression of target genes related to chemotactic migration of umbilical cord stem cells.
Example 10: behavioral and histopathological observations in rats
A rat knee Osteoarthritis (OA) model is established by injecting iodoacetic acid into a rat joint cavity, mechanical allodynia and thermal hyperalgesia methods are adopted to detect mechanical tenderness Threshold (TWL) and thermal hyperalgesia time (MWT) after combined intervention treatment of PL extracted from example 1 and umbilical cord stem cells cultured by the PL, bilateral knee joints of rats are dissected and taken, after decalcification treatment, rat cartilage sections are subjected to safranin-O staining and OARSI scoring, and 0.9% physiological saline, 0.625% PL, 1 × 10 are added6An MSC. Results as in fig. 5A, model group staining results show typical cartilage degeneration phenomena: chondrocyte loss and collagen destruction. After treatment with PL and umbilical cord stem cells, the recovery of chondrocytes and collagen reverses the degeneration to PL + MSC>MSC>PL. The OARSI score confirms that the model group score is obviously increased compared with the normal group level (P<0.05), and after PL + MSC, PL treatment, the score was significantly reduced compared to the model group (P<0.05). Rat behavioral results as shown in fig. 5B, OA model group significantly reduced TWL and MWT levels compared to normal levels (ii) ((ii))P<0.05). Significantly improved TWL and MWT levels after PL + MSC, MSC and PL treatment compared to model group ((M))P<0.05). PL + MSC, PL effects on TWL similar, whereas PL + MSC effects on MWT similar to MSCBut is superior to PL. Indicating that PL in combination with umbilical cord stem cells synergistically promotes osteoarthritic cartilage repair, the two having a combined effect.
Claims (5)
1. Use of platelet lysate as an adjunct to cord stem cells in promoting and enhancing cell therapy.
2. Use of platelet lysates for the proliferation, chemotaxis and regeneration of umbilical cord stem cells based on growth factors.
3. The use of platelet lysate to improve the viability and biological function of umbilical cord stem cells.
4. The application of the platelet lysate and umbilical cord stem cells in preparing a medicament for treating knee osteoarthritis.
5. The application of the platelet lysate and umbilical cord stem cells in preparing cartilage repair medicines for treating knee osteoarthritis.
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|---|---|---|---|---|
| CN117736982A (en) * | 2024-02-20 | 2024-03-22 | 广东先康达生物科技有限公司 | Adipose-derived mesenchymal stem cell composite preparation and preparation method and application thereof |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101945994A (en) * | 2007-12-19 | 2011-01-12 | 再生科学有限责任公司 | Compositions and methods to promote implantation and engrafment of stem cells |
| CN103352026A (en) * | 2013-07-24 | 2013-10-16 | 黑龙江天晴干细胞有限公司 | Method for cultivating autologous umbilical cord mesenchymal stem cells by adopting human umbilical cord blood rich platelet lysate |
| CN105441388A (en) * | 2015-12-15 | 2016-03-30 | 天津市康婷生物工程有限公司 | Method for promoting high expression of umbilical cord mesenchymal stem cell ossification regeneration key gene |
| CN108823156A (en) * | 2018-07-04 | 2018-11-16 | 陕西神州生物技术有限公司 | For the clinical grade human umbilical cord mesenchymal stem cells composite factor of reparation and the preparation method of freeze-dried powder |
| WO2019100175A1 (en) * | 2017-11-27 | 2019-05-31 | Regenero S.A. | Composition and method for the cultivation, expansion, preservation and/or pre-treatment of cells |
| CN110237095A (en) * | 2019-05-28 | 2019-09-17 | 武汉汉密顿生物科技股份有限公司 | For treating stem cell injection liquid and its preparation and the application of cartilage defect of osteoarthritis |
| CN111303270A (en) * | 2020-02-18 | 2020-06-19 | 浙江中医药大学 | Method for preparing platelet growth factor concentrate by using kit |
-
2020
- 2020-07-10 CN CN202010662169.9A patent/CN111759865A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101945994A (en) * | 2007-12-19 | 2011-01-12 | 再生科学有限责任公司 | Compositions and methods to promote implantation and engrafment of stem cells |
| CN103352026A (en) * | 2013-07-24 | 2013-10-16 | 黑龙江天晴干细胞有限公司 | Method for cultivating autologous umbilical cord mesenchymal stem cells by adopting human umbilical cord blood rich platelet lysate |
| CN105441388A (en) * | 2015-12-15 | 2016-03-30 | 天津市康婷生物工程有限公司 | Method for promoting high expression of umbilical cord mesenchymal stem cell ossification regeneration key gene |
| WO2019100175A1 (en) * | 2017-11-27 | 2019-05-31 | Regenero S.A. | Composition and method for the cultivation, expansion, preservation and/or pre-treatment of cells |
| CN108823156A (en) * | 2018-07-04 | 2018-11-16 | 陕西神州生物技术有限公司 | For the clinical grade human umbilical cord mesenchymal stem cells composite factor of reparation and the preparation method of freeze-dried powder |
| CN110237095A (en) * | 2019-05-28 | 2019-09-17 | 武汉汉密顿生物科技股份有限公司 | For treating stem cell injection liquid and its preparation and the application of cartilage defect of osteoarthritis |
| CN111303270A (en) * | 2020-02-18 | 2020-06-19 | 浙江中医药大学 | Method for preparing platelet growth factor concentrate by using kit |
Non-Patent Citations (8)
| Title |
|---|
| 华杰等: "血小板裂解液替代胎牛血清培养间充质干细胞", 《中国实验外科杂志》 * |
| 华杰等: "血小板裂解液替代胎牛血清培养间充质干细胞", 《中国实验外科杂志》, vol. 31, no. 4, 31 December 2014 (2014-12-31), pages 744 - 746 * |
| 哈承志等: "富血小板血浆联合间充质干细胞治疗膝骨关节炎的疗效", 《中华关节外科杂志(电子版)》, no. 05, 31 October 2018 (2018-10-31), pages 644 - 652 * |
| 沈克琦: "《分子生物学技术在中医药研究中的应用》", vol. 3, 上海科学技术出版社, pages: 173 - 30 * |
| 甘凤英等: "间充质干细胞移植治疗膝关节骨关节炎临床观察", 《现代诊断与治疗》 * |
| 甘凤英等: "间充质干细胞移植治疗膝关节骨关节炎临床观察", 《现代诊断与治疗》, no. 15, 31 August 2014 (2014-08-31), pages 3512 - 3513 * |
| 郑传睿等: "血小板裂解液联合脂肪干细胞干预大鼠膝骨关节炎的实验研究", 《中国中医骨伤科杂志》 * |
| 郑传睿等: "血小板裂解液联合脂肪干细胞干预大鼠膝骨关节炎的实验研究", 《中国中医骨伤科杂志》, 31 December 2019 (2019-12-31), pages 9 - 14 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117736982A (en) * | 2024-02-20 | 2024-03-22 | 广东先康达生物科技有限公司 | Adipose-derived mesenchymal stem cell composite preparation and preparation method and application thereof |
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