Department of Stem Cell Biology and Regenerative Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.
Department of Nephrology, Rakuwakai Otowa Hospital, Kyoto, Japan.
Commun Biol. 2021 May 14;4(1):575. doi: 10.1038/s42003-021-02082-5.
Diabetic neuropathy is an incurable disease. We previously identified a mechanism by which aberrant bone marrow-derived cells (BMDCs) pathologically expressing proinsulin/TNF-α fuse with residential neurons to impair neuronal function. Here, we show that CD106-positive cells represent a significant fraction of short-term hematopoietic stem cells (ST-HSCs) that contribute to the development of diabetic neuropathy in mice. The important role for these cells is supported by the fact that transplantation of either whole HSCs or CD106-positive ST-HSCs from diabetic mice to non-diabetic mice produces diabetic neuronal dysfunction in the recipient mice via cell fusion. Furthermore, we show that transient episodic hyperglycemia produced by glucose injections leads to abnormal fusion of pathological ST-HSCs with residential neurons, reproducing neuropathy in nondiabetic mice. In conclusion, we have identified hyperglycemia-induced aberrant CD106-positive ST-HSCs underlie the development of diabetic neuropathy. Aberrant CD106-positive ST-HSCs constitute a novel therapeutic target for the treatment of diabetic neuropathy.
糖尿病性神经病是一种无法治愈的疾病。我们之前发现了一种机制，即异常的骨髓来源细胞（BMDC）病理性表达胰岛素原/TNF-α并与居住神经元融合，从而损害神经元功能。在这里，我们表明 CD106 阳性细胞代表了短期造血干细胞（ST-HSCs）的重要部分，这些细胞有助于小鼠糖尿病性神经病的发展。这些细胞的重要作用得到了以下事实的支持：即从糖尿病小鼠向非糖尿病小鼠移植整个 HSCs 或 CD106 阳性 ST-HSCs 会通过细胞融合导致受体小鼠出现糖尿病性神经元功能障碍。此外，我们表明，葡萄糖注射引起的短暂发作性高血糖会导致病理性 ST-HSCs 与居住神经元的异常融合，从而在非糖尿病小鼠中重现神经病。总之，我们已经确定高血糖诱导的异常 CD106 阳性 ST-HSCs 是糖尿病性神经病发展的基础。异常的 CD106 阳性 ST-HSCs 构成了治疗糖尿病性神经病的新的治疗靶点。
