Impact of Type 2 Diabetes Mellitus on Human Bone Marrow Stromal Cell Number and Phenotypic Characteristics
Impact of Type 2 Diabetes Mellitus on Human Bone Marrow Stromal Cell Number and Phenotypic Characteristics
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DOI：
10.3390/ijms21072476
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发表时间：
2020-04-01
影响因子：
5.6
通讯作者：
Coleman, Cynthia M.
中科院分区：
文献类型：
--
作者：
Cassidy, Fearon C.;Shortiss, Ciara;Coleman, Cynthia M.
人骨髓间充质干细胞（MSC）已被研究在许多疾病的设置涉及受损的再生，因为他们在组织的维护和修复中发挥的关键作用。考虑到与2型糖尿病（T2DM）相关的合并症的数量，MSC通过减少其天然维护和修复活动介导这些合并症的假设是一个有趣的调查路线。在这里，证明了与年龄匹配的对照（AMC）供体相比，T2DM患者中骨髓来源的MSC的数量减少，这是由于具有成骨能力的MSC数量的特定减少。与AMC相比，T2DM供体的MSC细胞表面表型或MSC扩增、分化或血管生成或迁移能力无差异。这些发现阐明了MSC的基本生物学及其作为糖尿病合并症（尤其是骨病）介质的潜力，并为基于MSC的临床试验的供体选择提供了见解。这项研究表明，骨髓间充质干细胞作为2型糖尿病合并症的介质的任何作用可能是由于骨祖细胞群体大小的减少，而不是由于骨髓间充质干细胞通过扩增和分化维持组织稳态的能力的永久性改变。
Human bone marrow-derived mesenchymal stromal cells (MSCs) have been investigated in numerous disease settings involving impaired regeneration because of the crucial role they play in tissue maintenance and repair. Considering the number of comorbidities associated with type 2 diabetes mellitus (T2DM), the hypothesis that MSCs mediate these comorbidities via a reduction in their native maintenance and repair activities is an intriguing line of inquiry. Here, it is demonstrated that the number of bone marrow-derived MSCs in people with T2DM was reduced compared to that of age-matched control (AMC) donors and that this was due to a specific decrease in the number of MSCs with osteogenic capacity. There were no differences in MSC cell surface phenotype or in MSC expansion, differentiation, or angiogenic or migratory capacity from donors living with T2DM as compared to AMCs. These findings elucidate the basic biology of MSCs and their potential as mediators of diabetic comorbidities, especially osteopathies, and provide insight into donor choice for MSC-based clinical trials. This study suggests that any role of bone marrow MSCs as a mediator of T2DM comorbidity is likely due to a reduction in the osteoprogenitor population size and not due to a permanent alteration to the MSCs' capacity to maintain tissue homeostasis through expansion and differentiation.