Effects of transplantation of neural crest cells derived from iPS cells on diabetic polyneuropathy in mice

近年来的研究表明，神经嵴细胞移植治疗脊髓损伤是有效的。本研究使用老年小鼠iPS细胞NCCs治疗糖尿病多发性神经病变。用BMP4在PA6细胞上分化iPS细胞，p75阳性细胞定义为NCCs。将NCCs移植到stz -糖尿病小鼠后肢骨骼肌中。移植的NCCs在足底皮肤或比目鱼肌分化为血管平滑肌细胞或雪旺细胞。NCCs移植可改善糖尿病小鼠的神经功能损伤。此外，移植NCCs可增加糖尿病患者表皮内神经纤维密度，增加足底皮肤血流量和毛细血管。这些结果表明，移植来自iPS细胞的NCCs可能通过其分泌的生长因子的旁分泌作用，以及NCCs向雪旺细胞和血管平滑肌细胞的分化，对DPN有治疗作用。

Recent studies have shown that transplantation of neural crest cells (NCCs) is effective on spinal cord injury. Here we used NCCs from aged mouse iPS cells for treatment of diabetic polyneuropathy. iPS cells were differentiated on PA6 cells with BMP4 , and p75 positive cells were defined as NCCs. NCCs were transplanted into hind limb skeletal muscles of STZ-diabetic mice. Transplanted NCCs differentiated into vascular smooth muscle cells or Schwann cells in plantar skin or soleus muscle. Impaired nerve functions in diabetic mice were ameliorated by the transplantation of NCCs. In addition, transplantation of NCCs increased intraepidermal nerve fiber densities, plantar skin blood flow and capillaries in DM. These results suggest that transplantation of NCCs derived from iPS cells could have therapeutic effects on DPN through paracrine actions of growth factors secreted by NCCs and differentiation of NCCs into Schwann cells and vascular smooth muscle cells.