The Origin of the repaired cells and function of mesenchymal stem cell

本研究对修复细胞的来源及间充质干细胞在组织愈合中的作用进行了探讨。为了在体内跟踪移植细胞，建立了消除宿主对供体细胞免疫排斥的移植模型。首先，将不同种类的细胞移植到组织中，以验证该模型的完整性，并对移植细胞进行跟踪。然后，利用该移植模型研究间充质干细胞的分化。本研究以雌性转基因大鼠为供体，雌性野生型大鼠为受体。由于除转基因外，这些大鼠之间的DNA在理论上是一致的，因此可以通过对转基因大鼠细胞进行原位杂交的方法在受体组织中跟踪移植细胞。此外，由于使用的是转基因大鼠，它本来全身都含有转基因基因，因此不需要引入标记。使用这种具有抗BrdU免疫组化的新型移植模型，发现移植的滑膜细胞在关节中存活并增殖至少4周（Trans ORS 1998, Cell Tissue RES 1999）。结合新开发的微压头，还发现移植的骨软骨碎片中的供体细胞引起了内软骨的自我形成，并有助于粘弹性的恢复（Trans ORS 1999）。因此，该移植模型有利于使用生物学和生物力学方法进行组织修复的多学科研究。另一方面，骨髓是众所周知的间充质干细胞的来源。本研究将转基因大鼠的骨髓细胞移植到野生型大鼠损伤的膝关节内侧副韧带（MCL）中。形态学观察这些细胞的分化情况。结果表明，骨髓细胞分化为成纤维细胞。这些细胞也被发现迁移到中间物质中，并协助构成愈合的MCL （Hilton head workshop 1999）。少

In this study the origin of the repaired cells and the function of mesenchymal stem cells in tissue healing were examined. The transplantation model to eliminate the immunological rejection of the donor cells by the host was developed in order to follow transplanted cells in vivo. First, various kinds of cells were transplanted into tissues to prove the integrity of this model in following the transplanted cells. Then, the differentiation of mesenchymal stem cells was studied using this transplantation model. In this study, a female transgenic rat was used as a donor, and a female wild-type rat was used as a recipient. Since the DNA between these rats is theoretically coincident except for transgenes, transplanted cells could be followed in the recipient tissues by in situ hybridization against transgenes of transgenic rats cells. Furthermore, due to the use of the transgenic rat, which originally contains transgenes in the whole body, the introduction of markers is not necessary. Usin … More g this novel transplantation model with immunohistochemistry against BrdU, it was found that transplanted synovial cells survive and proliferate in the joint for at least 4 weeks (Trans ORS 1998, Cell Tissue RES 1999). By combining the newly developed micro-indentator, it was also found that donor cells in the transplanted osteochondral fragment caused the enchondral ontogenesis and helped in the recovery of viscoelastic properties (Trans ORS 1999). This transplantation model therefore was beneficial in performing multidisciplinary study on the repair of the tissue, using biological and biomechanical approaches. On the other hand, bone marrow is well known as a source of mesenchymal stem cells. In this study, bone marrow cells of the transgenic rat were transplanted into the injured medial collateral ligament (MCL) of the knee in the wild-type rat. The differentiation of these cells was morphologically examined. As a result, bone marrow cells were demonstrated to differentiate into fibroblasts. These cells were also found to migrate into the midsubstance and assisted in constitute the healing MCL (Hilton head workshop 1999). Less