Improvement of Mouse Osteoporotic Bone by Allogenic nd/or Xenogenic Mesenchymal Stem Cells Transplantation
Date Issued
2008
Date
2008
Author(s)
Peng, Shao-Yu
Abstract
It was estimated that patients suffered from osteoporosis worldwide were exceeding 200 millions in the year of 2006, and still increasing prevalently in the elderly and menopausal women. This illness, which causes serious bone fractures, leads to life threatening complications and greatly influences the quality of patients’ life. Osteoporosis is a result of imbalance between bone formation and resorption and gradually become a disease needs to be resolved urgently in the modern society. Osteoporosis is due to defect in mesenchymal stem cells (MSCs) that leads to reduce the ability to differentiate into osteoblast. For this reason, the objective of this study was to establish a mouse model of osteoporosis and investigate the feasibility of using allogenic or xenogenic bone marrow mesenchymal stem cells (BMMSCs) as therapeutic agents. C57/BL6 female mice at fifteen weeks of age were operated for ovariectomy to induce osteoporosis. Assays of bone sections and micro computed tomography (μCT) scan were performed to examine the bone density percentages on those animals six months post the ovariectomy. Bone sections could reveal the density of trabecular bone clearly dropped above and below the growth plate. μCT scan also showed bone density significant decreases: 15.0 ± 1.99% versus 9.7 ± 1.44% (P<0.05) indicating these mice has become osteoporosis.n addition, bone marrow derived MSCs obtained from transgenic mice and pigs harboring the enhanced fluorescent protein (EGFP) were treated with differentiating solution (0.1μM dexamethasone + 10 mM glycerol-2-phosphate + 50μM ascorbate-2-phosphate) and analyzed by BCIP/NBT and Alizarin Red S stains to confirm the potential of osteogenesis prior to the allogenic or xenogenic stem cells transplantations either through intravenously (IV) or intraperitoneally (IP), IV group has 7 osteoporotic mice and IP group has 5 osteoporotic mice for experiment respectively. The EGFP reporter was later used for tracing the migration fate of EGFP-m/pBMMSCs after they had been transplanted into osteoporotic mice, and also for further verifying those functions and differential potential of transplanted cells in vivo. The ability of migration and involvement of bone formation for EGFP-m/pBMMSCs were detected in the immunohistochemistry, bone section and and μCT scan. Increased bone density were observed in two out of five in allogenic IV: 35.09%、19.32%, one out of five in allogenic IP: 18.59%, two out of six in xenogenic IV: 13.27%、7.98% and one out five in xenogenic IP: 39.38%. Besides, some EGFP-m/pBMMSCs were found to remain in the bone marrow and might serve as a reservoir of bone progenitors which could be used for bone repairing later.he results indicated that EGFP-m/pBMMSCs were injected into osteoporotic mice by IV or IP were able to migrate into the bones and participate in the bone formation in vivo, display histologically the location of EGFP-m/pBMMSCs in bone, examined by GFP immuno-staining. Assay of pathogenic histology and μCT scan illustrated improved microstructures in newly formed trabecular bone tissue. Hence, allogenic or xenogenic BMMSCs possess the feasibility to be as a clinical therapeutic agent with an improved curative efficiency for treating osteoporosis in the foreseeable future.
Subjects
Transgenic mice
Transgenic pigs
Osteoporosis
Ovariectomy
Mesenchymal stem cells
Type
thesis
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