Department of Stem Cell Biology and Regenerative Medicine, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga, Japan.
Stem Cells Transl Med. 2023 Apr 17;12(4):215-220. doi: 10.1093/stcltm/szad015.
Diabetic neuropathy is a major complication of diabetes mellitus that occurs during the early stages of the disease. Many pathogenic mechanisms are related and induced by hyperglycemia. However, even if these factors improve, diabetic neuropathy cannot go into remission and progresses slowly. Furthermore, diabetic neuropathy often progresses even with proper glycemic control. Recently, bone marrow-derived cells (BMDCs) were reported to be involved in the pathogenesis of diabetic neuropathy. BMDCs expressing proinsulin and TNFα migrate to the dorsal root ganglion and fuse with neurons, and this neuronal-hematopoietic cell fusion induces neuronal dysfunction and apoptosis. The CD106-positive lineage-sca1+c-kit+ (LSK) stem cell fraction in the bone marrow is strongly involved in cell fusion with neurons, leading to diabetic neuropathy. Surprisingly, when CD106-positive LSK stem cells obtained from diabetic mice were transplanted into nondiabetic mice, they fused with dorsal root ganglion neurons and induced neuropathy in non-hyperglycemic normal mice. The transplanted CD106-positive LSK fraction inherited the trait even after transplantation; this "progeny effect" may explain the irreversibility of diabetic neuropathy and is a significant finding for determining the target of radical treatments and provides new directions for developing therapeutic methods for diabetic neuropathy.
糖尿病性神经病是糖尿病的一种主要并发症，发生于疾病的早期。许多发病机制与高血糖相关，并由其诱导。然而，即使这些因素得到改善，糖尿病性神经病也无法缓解并会缓慢进展。此外，即使血糖得到适当控制，糖尿病性神经病也常常会进展。最近，有报道称骨髓源性细胞（BMDC）参与了糖尿病性神经病的发病机制。表达胰岛素原和 TNFα的 BMDC 向背根神经节迁移并与神经元融合，这种神经元-造血细胞融合诱导神经元功能障碍和细胞凋亡。骨髓中 CD106 阳性谱系- Scal+ c-Kit+（LSK）干细胞亚群强烈参与与神经元的细胞融合，导致糖尿病性神经病。令人惊讶的是，当从糖尿病小鼠中获得的 CD106 阳性 LSK 干细胞移植到非糖尿病小鼠中时，它们与背根神经节神经元融合，并在非高血糖的正常小鼠中诱导神经病。移植的 CD106 阳性 LSK 亚群在移植后仍保留融合特性；这种“后代效应”可能解释了糖尿病性神经病的不可逆转性，是确定根治性治疗靶点的重要发现，并为开发糖尿病性神经病的治疗方法提供了新的方向。
