Mizukami Hiroki, Yagihashi Soroku
Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine , Hirosaki , Japan.
Front Endocrinol (Lausanne). 2014 Apr 9;5:45. doi: 10.3389/fendo.2014.00045. eCollection 2014.
Diabetic polyneuropathy (DPN) is the most common complication that emerges early in diabetic patients. Intervention with strict blood glucose control or treatment with aldose reductase inhibitor is reported to be effective in early stages of DPN. Curative treatment for overt or symptomatic DPN, however, has not been established, thus requiring much effort to explore a new therapy. Recent preclinical studies on the use of gene or cell therapy have provided promising results in the treatment of DPN. Of particular interest, induced pluripotent stem cells are introduced. In these studies, restoration of DPN was proposed to be attributed to either neurotrophic factors released from transplanted stem cells or differentiation of stem cells to substitute the damaged peripheral nerve. There are still several problems, however, that remain to be overcome, such as perturbed function, fragility, or limited survival of transplanted cells in diabetes milieu and risk for malignant transformation of transplanted cells. Questions, which cell is the most appropriate as the source for cell therapy, or which site is the best for transplantation to obtain the most effective results, remain to be answered. In this communication, we overview the current status of preclinical studies on the cell therapy for DPN and discuss the future prospect.
糖尿病性多发性神经病变(DPN)是糖尿病患者早期出现的最常见并发症。据报道,严格控制血糖或使用醛糖还原酶抑制剂进行干预在DPN早期阶段是有效的。然而,对于明显的或有症状的DPN的根治性治疗尚未确立,因此需要付出很多努力来探索新的治疗方法。最近关于基因或细胞治疗应用的临床前研究在DPN治疗方面取得了有前景的结果。特别值得关注的是诱导多能干细胞的引入。在这些研究中,DPN的恢复被认为要么归因于移植干细胞释放的神经营养因子,要么归因于干细胞分化以替代受损的周围神经。然而,仍然存在几个有待克服的问题,例如在糖尿病环境中移植细胞的功能紊乱、脆弱性或有限的存活率以及移植细胞恶性转化的风险。哪种细胞作为细胞治疗的最佳来源,或者哪个部位是获得最有效结果的最佳移植部位等问题仍有待解答。在本通讯中,我们概述了DPN细胞治疗临床前研究的现状并讨论了未来前景。