Krebsbach P H, Mankani M H, Satomura K, Kuznetsov S A, Robey P G
University of Michigan, School of Dentistry, Ann Arbor 48109-1078, USA.
Transplantation. 1998 Nov 27;66(10):1272-8. doi: 10.1097/00007890-199811270-00002.
Techniques used to repair craniofacial skeletal defects parallel the accepted surgical therapies for bone loss elsewhere in the skeleton and include the use of autogenous bone and alloplastic materials. Transplantation of a bone marrow stromal cell population that contains osteogenic progenitor cells may be an additional modality for the generation of new bone.
Full thickness osseous defects (5 mm) were prepared in the cranium of immunocompromised mice and were treated with gelatin sponges containing murine alloplastic bone marrow stromal cells derived from transgenic mice carrying a type I collagen-chloramphenicol acetyltransferase reporter gene to follow the fate of the transplanted cells. Control surgical sites were treated with spleen stromal cells or gelatin sponges alone, or were left untreated. The surgical defects were analyzed histologically for percent closure of the defect at 2, 3, 4, 6, and 12 weeks.
Cultured bone marrow stromal cells transplanted within gelatin sponges resulted in osteogenesis that repaired greater than 99.0+/-2.20% of the original surgical defect within 2 weeks. In contrast, cranial defects treated with splenic fibroblasts, vehicle alone, or sham-operated controls resulted in minimal repair that was limited to the surgical margins. Bone marrow stromal cells carrying the collagen transgene were immunodetected only in the newly formed bone and thus confirmed the donor origin of the transplanted cells.
These studies demonstrate that mitotically expanded bone marrow cells can serve as an abundant source of osteoprogenitor cells that are capable of repairing craniofacial skeletal defects in mice without the addition of growth or morphogenetic factors.
用于修复颅面骨骼缺损的技术与骨骼其他部位公认的骨丢失手术治疗方法相似,包括使用自体骨和异体材料。移植含有成骨祖细胞的骨髓基质细胞群体可能是生成新骨的另一种方式。
在免疫功能低下小鼠的颅骨上制备全层骨缺损(5毫米),并用含有源自携带I型胶原-氯霉素乙酰转移酶报告基因的转基因小鼠的鼠异体骨髓基质细胞的明胶海绵进行处理,以追踪移植细胞的命运。对照手术部位用脾基质细胞或单独的明胶海绵处理,或不进行处理。在2、3、4、6和12周时对手术缺损进行组织学分析,以确定缺损的闭合百分比。
在明胶海绵内移植培养的骨髓基质细胞导致成骨,在2周内修复了超过99.0±2.20%的原始手术缺损。相比之下,用脾成纤维细胞、单独的载体或假手术对照组处理的颅骨缺损导致的修复极少,仅限于手术边缘。仅在新形成的骨中免疫检测到携带胶原转基因的骨髓基质细胞,从而证实了移植细胞的供体来源。
这些研究表明,经有丝分裂扩增的骨髓细胞可作为丰富的成骨祖细胞来源,能够在不添加生长或形态发生因子的情况下修复小鼠的颅面骨骼缺损。