Concise Review: Musculoskeletal Stem Cells to Treat Age-Related Osteoporosis.
Concise Review: Musculoskeletal Stem Cells to Treat Age-Related Osteoporosis.
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DOI：
10.1002/sctm.17-0054
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发表时间：
2017-10
影响因子：
6
通讯作者：
Stanford WL
中科院分区：
文献类型：
--
作者：
Kiernan J;Davies JE;Stanford WL
年龄相关性（II型）骨质疏松症是一种常见的使人衰弱的疾病，部分原因是骨髓（BM）间充质基质细胞（MSC）及其成骨细胞后代的丢失，导致骨形成减少。目前针对年龄相关性骨质疏松症的药物治疗方案并不通过增加骨形成来直接治疗该疾病，而是使用双膦酸盐来减少骨吸收-一种针对绝经后（I型）骨质疏松症的治疗方法。最近，MSC的骨再生能力已被发现存在于更大的异质BM-MSC池中的非常罕见的骨骼干细胞（SSC）群体中。SSC的骨再生潜力将是基于细胞的疗法治疗退行性骨疾病（如骨质疏松症）的理想候选者。然而，到目前为止，临床和转化研究试图通过细胞移植来改善骨形成，使用了更大的，非特异性的MSC池。在这篇综述中，我们将概述与年龄相关的骨质疏松症的生理基础，并讨论使用外源性MSC移植治疗小鼠模型骨质疏松症的相关临床前研究。我们还将讨论旨在治疗其他全身性骨疾病的特定临床试验的结果，以及SSC的发现如何有助于实现MSC治疗的全部再生潜力，以增加骨形成。最后，我们将概述如何启动辅助临床试验，以评估现有和潜在无关临床试验中MSC/SSC介导的骨形成增益，为治疗年龄相关性骨质疏松症的专门临床研究奠定基础。干细胞转化医学2017;6：1930-1939
Age‐related (type‐II) osteoporosis is a common and debilitating condition driven in part by the loss of bone marrow (BM) mesenchymal stromal cells (MSC) and their osteoblast progeny, leading to reduced bone formation. Current pharmacological regiments targeting age‐related osteoporosis do not directly treat the disease by increasing bone formation, but instead use bisphosphonates to reduce bone resorption—a treatment designed for postmenopausal (type‐I) osteoporosis. Recently, the bone regenerative capacity of MSCs has been found within a very rare population of skeletal stem cells (SSCs) residing within the larger heterogeneous BM‐MSC pool. The osteoregenerative potential of SSCs would be an ideal candidate for cell‐based therapies to treat degenerative bone diseases such as osteoporosis. However, to date, clinical and translational studies attempting to improve bone formation through cell transplantation have used the larger, nonspecific, MSC pool. In this review, we will outline the physiological basis of age‐related osteoporosis, as well as discuss relevant preclinical studies that use exogenous MSC transplantation with the aim of treating osteoporosis in murine models. We will also discuss results from specific clinical trials aimed at treating other systemic bone diseases, and how the discovery of SSC could help realize the full regenerative potential of MSC therapy to increase bone formation. Finally, we will outline how ancillary clinical trials could be initiated to assess MSC/SSC‐mediated bone formation gains in existing and potentially unrelated clinical trials, setting the stage for a dedicated clinical investigation to treat age‐related osteoporosis. Stem Cells Translational Medicine 2017;6:1930–1939
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影响因子：
5.2
作者：
Bartosh, Thomas J.;Yloestalo, Joni H.;Bazhanov, Nikolay;Kuhlman, Jessica;Prockop, Darwin J.
通讯作者：
Prockop, Darwin J.
影响因子：
2.8
作者：
Chen H;Zhou X;Fujita H;Onozuka M;Kubo KY
通讯作者：
Kubo KY
影响因子：
4.3
作者：
Brennan TA;Egan KP;Lindborg CM;Chen Q;Sweetwyne MT;Hankenson KD;Xie SX;Johnson FB;Pignolo RJ
通讯作者：
Pignolo RJ
影响因子：
6.2
作者：
Chen, XD;Shi, ST;Young, MF
通讯作者：
Young, MF
影响因子：
6.7
作者：
Beyth, Shaul;Schroeder, Josh;Liebergall, Meir
通讯作者：
Liebergall, Meir