Wakitani S, Goto T, Pineda S J, Young R G, Mansour J M, Caplan A I, Goldberg V M
Department of Orthopaedics, Case Western Reserve University School of Medicine, University Hospitals of Cleveland, Ohio 44106.
J Bone Joint Surg Am. 1994 Apr;76(4):579-92. doi: 10.2106/00004623-199404000-00013.
Osteochondral progenitor cells were used to repair large, full-thickness defects of the articular cartilage that had been created in the knees of rabbits. Adherent cells from bone marrow, or cells from the periosteum that had been liberated from connective tissue by collagenase digestion, were grown in culture, dispersed in a type-I collagen gel, and transplanted into a large (three-by-six-millimeter), full-thickness (three-millimeter) defect in the weight-bearing surface of the medial femoral condyle. The contralateral knee served as a control: either the defect in that knee was left empty or a cell-free collagen gel was implanted. The periosteal and the bone-marrow-derived cells showed similar patterns of differentiation into articular cartilage and subchondral bone. Specimens of reparative tissue were analyzed with use of a semiquantitative histological grading system and by mechanical testing with employment of a porous indenter to measure the compliance of the tissue at intervals until twenty-four weeks after the operation. There was no apparent difference between the results obtained with the cells from the bone marrow and those from the periosteum. As early as two weeks after transplantation, the autologous osteochondral progenitor cells had uniformly differentiated into chondrocytes throughout the defects. This repair cartilage was subsequently replaced with bone in a proximal-to-distal direction, until, at twenty-four weeks after transplantation, the subchondral bone was completely repaired, without loss of overlying articular cartilage. The mechanical testing data were a useful index of the quality of the long-term repair. Twenty-four weeks after transplantation, the reparative tissue of both the bone-marrow and the periosteal cells was stiffer and less compliant than the tissue derived from the empty defects but less stiff and more compliant than normal cartilage.
The current modalities for the repair of defects of the articular cartilage have many disadvantages. The transplantation of progenitor cells that will form cartilage and bone offers a possible alternative to these methods. As demonstrated in this report, autologous, bone-marrow-derived, osteochondral progenitor cells can be isolated and grown in vitro without the loss of their capacity to differentiate into cartilage or bone. Sufficient autologous cells can be generated to initiate the repair of articular cartilage and the reformation of subchondral bone. The repair tissues appear to undergo the same developmental transitions that originally led to the formation of articular tissue in the embryo.(ABSTRACT TRUNCATED AT 400 WORDS)
采用骨软骨祖细胞修复兔膝关节所形成的大面积全层关节软骨缺损。将来自骨髓的贴壁细胞或经胶原酶消化从结缔组织中分离出的骨膜细胞进行培养,分散于I型胶原凝胶中,然后移植到股骨内侧髁负重面一个大的(3×6毫米)、全层(3毫米)缺损处。对侧膝关节作为对照:该膝关节的缺损处要么保持空缺,要么植入无细胞的胶原凝胶。骨膜来源的细胞和骨髓来源的细胞在分化为关节软骨和软骨下骨方面表现出相似的模式。使用半定量组织学分级系统对修复组织标本进行分析,并通过使用多孔压头进行力学测试,以每隔一段时间测量组织的顺应性,直至术后24周。骨髓来源的细胞和骨膜来源的细胞所获得的结果之间没有明显差异。早在移植后两周,自体骨软骨祖细胞就已在整个缺损处均匀分化为软骨细胞。随后,这种修复性软骨在从近端到远端的方向上被骨替代,直到移植后24周,软骨下骨完全修复,上方的关节软骨未丢失。力学测试数据是长期修复质量的有用指标。移植后24周,骨髓细胞和骨膜细胞的修复组织比空缺缺损处的组织更硬且顺应性更低,但比正常软骨更软且顺应性更高。
目前用于修复关节软骨缺损的方法有许多缺点。移植能够形成软骨和骨的祖细胞为这些方法提供了一种可能的替代方案。如本报告所示,自体骨髓来源的骨软骨祖细胞可以在体外分离和培养,而不会丧失其分化为软骨或骨的能力。可以产生足够的自体细胞来启动关节软骨的修复和软骨下骨的重塑。修复组织似乎经历了与胚胎中最初导致关节组织形成相同的发育转变。(摘要截取自400字)