美国斯坦福大学医学院Charles K. F. Chan和Michael T. Longaker研究组合作取得一项新成果。经过不懈努力，他们发现激活的骨骼干细胞可再生发育为关节软骨。这一研究成果于2020年8月17日发表在《自然-医学》上。

研究人员探究了驻留骨骼干细胞（SSC）亚群随年龄变化再生为软骨的能力，年龄可能是骨关节炎（OA）进展的可能因素。研究人员证明衰老与小鼠和人类关节中SSC的进行性丧失和软骨生成减少有关。

但是，通过使用微骨折（MF）手术刺激再生反应，成年小鼠肢关节的软骨表面仍可产生SSC的局部扩展。尽管MF诱导的SSC倾向于形成纤维组织，但在水凝胶中BMP2和可溶性VEGFR1（sVEGFR1）（一种VEGF受体拮抗剂）的局部共传递使MF激活的SSC有向关节软骨分化的倾向。这些数据表明在MF后，可诱导驻留干细胞亚群产生软骨以治疗OA中的局部软骨病。

据了解，OA是由不可逆的进行性关节软骨破坏导致的退化性疾病。造成OA的病因复杂，包括遗传易感性、急性损伤和慢性炎症等。

附：英文原文

Title: Articular cartilage regeneration by activated skeletal stem cells

Author: Matthew P. Murphy, Lauren S. Koepke, Michael T. Lopez, Xinming Tong, Thomas H. Ambrosi, Gunsagar S. Gulati, Owen Marecic, Yuting Wang, Ryan C. Ransom, Malachia Y. Hoover, Holly Steininger, Liming Zhao, Marcin P. Walkiewicz, Natalina Quarto, Benjamin Levi, Derrick C. Wan, Irving L. Weissman, Stuart B. Goodman, Fan Yang, Michael T. Longaker, Charles K. F. Chan

Issue&Volume: 2020-08-17

Abstract: Osteoarthritis (OA) is a degenerative disease resulting in irreversible, progressive destruction of articular cartilage1. The etiology of OA is complex and involves a variety of factors, including genetic predisposition, acute injury and chronic inflammation2,3,4. Here we investigate the ability of resident skeletal stem-cell (SSC) populations to regenerate cartilage in relation to age, a possible contributor to the development of osteoarthritis5,6,7. We demonstrate that aging is associated with progressive loss of SSCs and diminished chondrogenesis in the joints of both mice and humans. However, a local expansion of SSCs could still be triggered in the chondral surface of adult limb joints in mice by stimulating a regenerative response using microfracture (MF) surgery. Although MF-activated SSCs tended to form fibrous tissues, localized co-delivery of BMP2 and soluble VEGFR1 (sVEGFR1), a VEGF receptor antagonist, in a hydrogel skewed differentiation of MF-activated SSCs toward articular cartilage. These data indicate that following MF, a resident stem-cell population can be induced to generate cartilage for treatment of localized chondral disease in OA.

DOI: 10.1038/s41591-020-1013-2

Source: https://www.nature.com/articles/s41591-020-1013-2