| Tissue engineering is a new cross discipline which combines the basic theories and basic techniques of biology, medicine and engineering, showing promising future. Mesenchymal Stem Cells (MSCs) based tissue engineering technology was used in this research to treat 2 sports associated soft tissues problems----Stress Urinary Incontinence (SUI) and articular cartilage defects.In the people over 60 years old, approximately 30% women and 15% men suffer from urinary incontinence worldwide. Urinary incontinence could be divided into stress urinary incontinence, urge urinary, mixed urinary incontinence etc., among which SUI is the most common, accounting for 50%-70%. SUI is the disease that urine flows out invonluntarily because of impaired strength of sphincter of urethra when intraabdominal pressure increases. The common surgical treatment of SUI is placing a tension-free sling between mid-urethra and paries anterior vaginase. This experiment was designed to repair SUI with bone marrow Mesenchymal Stem Cells (bMSCs)/silk sling composite.The injuries of articular cartilage are common and often lead to disability of people, while the spontaneous reparative effectiveness is limited. The common treatments like debridement, drilling, microfracture, cartilage implantation etc. have good reparative effectiveness in short term but have unsatisfactory results in the long run. Recent years, a new therapy named Autologous Chondrocyte Implantation (ACI) makes the patients hopeful. Though ACI shows promising prospect, there are a number of problems in it. For example, there is limited source of chondrocytes, and when cultured in vitro, chondrocytes are prone to lose their phenotype. ACI will make an injury in the healthy cartilage of donor part. Because of these disadvantages, adult Mesenchymal Stem Cells (MSCs) are studied as seed cells to treat cartilage defects in lots of research. We are trying to find the new suitable seed cells for cartilage tissue engineering. Embryonic Stem Cells (ESCs) could differentiate into all types of cells in the body. Moreover, it was demonstrated that after transfected with some factors, like ESCs, somatic cells could differentiate into all types of cells in the body. These pluripotent cells are called induced Pluripoten Stem cells (iPS). Directly using iPS or ESCs as seed cells, teratomas were easily formed, so we used iPS-derived MSCs (iPS-MSCs) or ESCs-derived MSCs (ESC-MSCs) as seed cells to treat articular cartilage defects.The research consisted of three parts:Firstly, investigarion of the repair of SUI with bMSCs/silk scaffold composite; Secondly,investigation of the repair of articular cartilage defects with iPS-MSCs; Thirdly, investigation of the repair of articular cartilage defects with human ESC-MSCs (hESC-MSCs).Partâ… :Repair of SUI with bMSCs/silk scaffold compositeOBJECTIVE:To explore the application of bMSCs/silk in female SUI.METHODS:40 rats were divided into 4 groups. Group A, sham operation. Other three groups underwent bilateral proximal sciatic nerve transection (PSNT) and were confirmed SUI by the leak point pressure (LPP) measurement at 4 weeks after PSNT. Then, Group B had no sling placed; Group C was treated with a silk sling; and Group D was treated with a bMSC-based silk sling. LPP and histology were done 4 weeks post-operation, while collagen content test, mechanical test and histology were done 12 weeks post-operation. RESULTS:The LPP of Group C and Group D was nearly normal (shown in Group A), which was significantly higher than that of Group B. Histological results showed better collagen integration with the urethra tissue in Group D than in Group C. The collagen content and mechanical properties were both higher in Group D than in Group C. CONCLUSIONS:Silk sling alone and bMSCs-based tissue engineering silk sling both could treat SUI effectively, while the latter showed better propeties.Part II:Repair of articular cartilage defects with iPS-MSCsOBJECTIVE:To explore the results of using iPS-MSCs to repair the articular cartilage defects.METHODS:iPS-MSCs were induced with chondrogenic medium in the pellet system for 3 days. Full-thickness cartilage defects (diameter=2mm, thickness=2mm) were made in the patellar grooves of both knees of SD rats (n=6). The cartilage defects in left knees were left untreated serving as control group while the cartilage defects in the right knees were treated with pellets of iPS-MSCs. The rats were sacrificed at 4 and 8 weeks after transplantation respectively. The samples were examined with gross observation and histology.RESULTS:The GAG (glycosaminoglycan) was more and the treatment effectiveness was better in control group than in experiment group. The growth plates were normal in control group while they were destroyed in experiment group.CONCLUSIONS:iPS-MSCs held poor chondrogenic ability in the microenvironment of articular cartilage defects, they are not suitable seed cells to treat cartilage defects. Partâ…¢:Repair of articular cartilage defects with hESC-MSCsOBJECTIVE:To explore the results of using hESC-MSCs with Bone Morphogenetic Protein 7 (BMP7) in collagen scaffolds to repair the cartilage defects.METHODS:Full-thickness cartilage defects (diameter=2mm, thickness=2mm) were made in the patellar grooves of both knees of SD rats. The rats were randomly divided into 3 group, Group A:collagen scaffold group; Group B:collagen scaffold seeded with hESC-MSCs group; Group C:collagen scaffold seeded with hESC-MSCs and BMP7 group. The rats were sacrificed at 4 and 8 weeks after transplantation respectively. The samples were examined with gross observation and the samples of 8 weeks were examined with histological observation.RESULTS:The treatment effectiveness was worst in Group A, and that of Group B was better than that of Group A. The treatment effectiveness was best in Group C.CONCLUSIONS:Our results demonstrated that hESC-MSCs could improve the regeneration of articular cartilage tissues. They acted synergistically with BMP7 in stimulating the formation of hyaline cartilage tissues.
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