Bruder S P, Fink D J, Caplan A I
Osiris Therapeutics, Inc., Cleveland, Ohio 44106.
J Cell Biochem. 1994 Nov;56(3):283-94. doi: 10.1002/jcb.240560303.
Bone formation in the embryo, and during adult fracture repair and remodeling, involves the progeny of a small number of cells called mesenchymal stem cells (MSCs). These cells continuously replicate themselves, while a portion become committed to mesenchymal cell lineages such as bone, cartilage, tendon, ligament, and muscle. The differentiation of these cells, within each lineage, is a complex multistep pathway involving discrete cellular transitions much like that which occurs during hematopoiesis. Progression from one stage to the next depends on the presence of specific bioactive factors, nutrients, and other environmental cues whose exquisitely controlled contributions orchestrate the entire differentiation phenomenon. An understanding of the cellular and molecular events of osteogenic differentiation of MSCs provides the foundation for the emergence of a new therapeutic technology for cell therapy. The isolation and in vitro mitotic expansion of autologous human MSCs will support the development of novel protocols for the treatment of many clinically challenging conditions. For example, local bone defects can be repaired through site-directed delivery of MSCs in an appropriate carrier vehicle. Generalized conditions, such as osteoporosis, may be treatable by systemic administration of culture-expanded autologous MSCs or through biopharmaceutical regimens based on the discovery of critical regulatory molecules in the differentiation process. With this in mind, we can begin to explore therapeutic options that have never before been available.
胚胎期以及成年期骨折修复和重塑过程中的骨形成，涉及一小部分被称为间充质干细胞（MSC）的细胞后代。这些细胞不断自我复制，同时一部分细胞会分化为间充质细胞谱系，如骨、软骨、肌腱、韧带和肌肉。在每个谱系中，这些细胞的分化是一个复杂的多步骤过程，涉及离散的细胞转变，这与造血过程中发生的情况非常相似。从一个阶段发展到下一个阶段取决于特定生物活性因子、营养物质和其他环境信号的存在，这些因素的精确控制作用协调了整个分化现象。对MSC成骨分化的细胞和分子事件的理解为细胞治疗新治疗技术的出现奠定了基础。自体人MSC的分离和体外有丝分裂扩增将支持开发用于治疗许多临床挑战性疾病的新方案。例如，局部骨缺损可以通过在合适的载体中定点递送MSC来修复。全身性疾病，如骨质疏松症，可能可以通过全身给予培养扩增的自体MSC或基于分化过程中关键调节分子的发现的生物制药方案来治疗。考虑到这一点，我们可以开始探索以前从未有过的治疗选择。
