Knight M Noelle, Hankenson Kurt D
Veterinary Medical Scientist Training Program, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, Pennsylvania. ; Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.
Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, Pennsylvania. ; Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.
Adv Wound Care (New Rochelle). 2013 Jul;2(6):306-316. doi: 10.1089/wound.2012.0420.
Mesenchymal stem cells (MSCs) play a key role in fracture repair by differentiating to become bone-forming osteoblasts and cartilage-forming chondrocytes. Cartilage then serves as a template for additional bone formation through the process of endochondral ossification.
Endogenous MSCs that contribute to healing are primarily derived from the periosteum, endosteum, and marrow cavity, but also may be contributed from the overlying muscle or through systemic circulation, depending on the type of injury. A variety of growth factor signaling pathways, including BMP, Wnt, and Notch signaling, influence MSC proliferation and differentiation. These MSCs can be therapeutically manipulated to promote differentiation. Furthermore, MSCs can be harvested, cultivated, and delivered to promote bone healing.
Pharmacologically manipulating the number and differentiation capacity of endogenous MSCs is one potential therapeutic approach to improve healing; however, ideal agents to influence signaling pathways need to be developed and additional therapeutics that activate endogenous MSCs are needed. Whether isolated and purified, MSCs participate directly in the healing process or serve a bystander effect and indirectly influence healing is not well defined.
Studies must focus on better understanding the regulation of endogenous MSCs durings fracture healing. This will reveal novel molecules and pathways to therapeutically target. Similarly, while animal models have demonstrated efficacy in the delivery of MSCs to promote healing, more research is needed to understand ideal donor cells, cultivation methods, and delivery before stem cell therapy approaches can be utilized to repair bone.
间充质干细胞（MSCs）在骨折修复中发挥关键作用，可分化为成骨的成骨细胞和形成软骨的软骨细胞。然后，软骨通过软骨内成骨过程作为额外骨形成的模板。
有助于愈合的内源性MSCs主要来源于骨膜、骨内膜和骨髓腔，但也可能来源于覆盖的肌肉或通过全身循环，这取决于损伤的类型。多种生长因子信号通路，包括骨形态发生蛋白（BMP）、Wnt和Notch信号通路，影响MSCs的增殖和分化。这些MSCs可通过治疗手段进行调控以促进分化。此外，MSCs可以采集、培养并用于促进骨愈合。
通过药理学手段调控内源性MSCs的数量和分化能力是改善愈合的一种潜在治疗方法；然而，需要开发影响信号通路的理想药物，并且需要更多激活内源性MSCs的治疗方法。无论是否分离和纯化，MSCs是直接参与愈合过程还是起旁观者效应并间接影响愈合尚不清楚。
研究必须集中于更好地理解骨折愈合过程中内源性MSCs的调控机制。这将揭示新的可作为治疗靶点的分子和信号通路。同样，虽然动物模型已证明在递送MSCs促进愈合方面具有疗效，但在干细胞治疗方法可用于修复骨之前，还需要更多研究来了解理想的供体细胞、培养方法和递送方式。
