Emerging therapy for diabetic neuropathy: cell therapy targeting vessels and nerves.
Emerging therapy for diabetic neuropathy: cell therapy targeting vessels and nerves.
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DOI：
10.2174/187153012800493486
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发表时间：
2012-06
期刊：
影响因子：
--
通讯作者：
Yoon YS
中科院分区：
文献类型：
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作者：
Kim H;Kim JJ;Yoon YS
糖尿病神经病变（DN）是糖尿病最常见的并发症，经常导致足部溃疡，并可能发展至截肢。尽管发病率不断增加，但临床上尚无有效治疗 DN 的疗法。从发病机制上来说，DN 的特点是周围神经血管减少以及血管生成因子和神经营养因子缺乏。我们将简要回顾 DN 的发病机制，并讨论细胞疗法对 DN 的作用和机制。为了逆转 DN 的变化，研究尝试以蛋白质或基因疗法的形式提供神经营养或血管生成因子进行治疗；然而，事实证明，即使不是无效，效果也是非常有限的。最近的研究表明，骨髓（BM）来源的细胞如单核细胞或内皮祖细胞（EPC）可以通过其旁分泌作用有效治疗各种心血管疾病。由于骨髓来源的细胞包含多种血管生成和神经营养细胞因子，这些细胞被用于治疗实验性 DN，并发现可以逆转 DN 的表现。特别是，EPCs 通过增强神经新生血管形成和神经保护作用而发挥良好的治疗效果。这些发现清楚地表明 DN 是一种复杂的疾病，其发病机制涉及血管和神经成分。研究表明，针对血管和神经元件的细胞疗法在治疗 DN 方面具有优势。
Diabetic neuropathy (DN), the most common complication of diabetes, frequently leads to foot ulcers and may progress to limb amputations. Despite continuous increase in incidence, there is no clinical therapy to effectively treat DN. Pathogenetically, DN is characterized by reduced vascularity in peripheral nerves and deficiency in angiogenic and neurotrophic factors. We will briefly review the pathogenetic mechanism of DN and address the effects and the mechanisms of cell therapies for DN. To reverse the changes of DN, studies have attempted to deliver neurotrophic or angiogenic factors for treatment in the form of protein or gene therapy; however, the effects turned out to be very modest if not ineffective. Recent studies have demonstrated that bone marrow (BM)-derived cells such as mononuclear cells or endothelial progenitor cells (EPCs) can effectively treat various cardiovascular diseases through their paracrine effects. As BM-derived cells include multiple angiogenic and neurotrophic cytokines, these cells were used for treating experimental DN and found to reverse manifestations of DN. Particularly, EPCs were shown to exert favorable therapeutic effects through enhanced neural neovascularization and neuro-protective effects. These findings clearly indicate that DN is a complex disorder with pathogenetic involvement of both vascular and neural components. Studies have shown that cell therapies targeting both vascular and neural elements are shown to be advantageous in treating DN.