Tendon progenitor cells in injured tendons have strong chondrogenic potential: the CD105-negative subpopulation induces chondrogenic degeneration.
Tendon progenitor cells in injured tendons have strong chondrogenic potential: the CD105-negative subpopulation induces chondrogenic degeneration.
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DOI：
10.1002/stem.1847
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发表时间：
2014-12
期刊：
影响因子：
5.2
通讯作者：
Enomoto-Iwamoto, Motomi
中科院分区：
文献类型：
--
作者：
Asai, Shuji;Otsuru, Satoru;Candela, Maria Elena;Cantley, Leslie;Uchibe, Kenta;Hofmann, Ted J.;Zhang, Kairui;Wapner, Keith L.;Soslowsky, Louis J.;Horwitz, Edwin M.;Enomoto-Iwamoto, Motomi
为了研究跟腱修复过程的细胞机制，我们使用小鼠跟腱损伤模型来关注损伤部位的细胞募集。通过集落形成能力、细胞表面标记物和多能性测定，术后1周从损伤肌腱和未损伤肌腱中分离的细胞含有结缔组织祖细胞群。将损伤的肌腱源性祖细胞（inTPCs）移植到损伤的跟腱中，它们不仅在表达成腱表型的再生区整合，而且在退行性病变中进行异位软骨内成骨，并向软骨细胞分化。令人惊讶的是，即使在缺乏外源性bmp或TGFβs的情况下，intpc的微质量培养也能迅速发生软骨分化。从人肌腱断裂组织中分离的细胞也表现出结缔组织祖细胞的特性，并表现出比骨髓基质细胞更强的成软骨能力。小鼠intpc包含两个亚群，一个是CD105阳性，一个是CD105阴性，CD105是TGFβ超家族的共同受体。与cd105阳性细胞相比，cd105阴性细胞在体外表现出更强的成软骨潜能，并在小鼠中诱导更大的软骨变性病变。这些发现表明，肌腱祖细胞被募集到肌腱损伤部位，具有很强的成软骨潜能，这些细胞的cd105阴性群体可能是损伤肌腱软骨样变性的原因。新发现的细胞招募到受伤的肌腱可能提供新的靶点，以制定治疗策略，促进肌腱修复。
To study the cellular mechanism of the tendon repair process, we used a mouse Achilles tendon injury model to focus on the cells recruited to the injured site. The cells isolated from injured tendon 1 week after the surgery and uninjured tendons contained the connective tissue progenitor populations as determined by colony-forming capacity, cell surface markers and multipotency. When the injured tendon-derived progenitor cells (inTPCs) were transplanted into injured Achilles tendons, they were not only integrated in the regenerating area expressing tenogenic phenotype but also trans-differentiated into chondrogenic cells in the degenerative lesion that underwent ectopic endochondral ossification. Surprisingly, the micromass culture of the inTPCs rapidly underwent chondrogenic differentiation even in the absence of exogenous BMPs or TGFβs. The cells isolated from human ruptured tendon tissues also showed connective tissue progenitor properties and exhibited stronger chondrogenic ability than bone marrow stromal cells. The mouse inTPCs contained two subpopulations one positive and one negative for CD105, a co-receptor of the TGFβ superfamily. The CD105-negative cells showed superior chondrogenic potential in vitro and induced larger chondroid degenerative lesions in mice as compared to the CD105-positive cells. These findings indicate that tendon progenitor cells are recruited to the injured site of tendons and have a strong chondrogenic potential and that the CD105-negative population of these cells would be the cause for chondroid degeneration in injured tendons. The newly identified cells recruited to the injured tendon may provide novel targets to develop therapeutic strategies to facilitate tendon repair.
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影响因子：
20.3
作者：
Otsuru, Satoru;Gordon, Patricia L.;Horwitz, Edwin M.
通讯作者：
Horwitz, Edwin M.
影响因子：
82.9
作者：
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通讯作者：
Young, Marian F.
影响因子：
7
作者：
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影响因子：
4.8
作者：
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通讯作者：
Chan, Kai Ming
影响因子：
2.3
作者：
Liu R;Birke O;Morse A;Peacock L;Mikulec K;Little DG;Schindeler A
通讯作者：
Schindeler A