Cell Reprogram：首次将糖尿病足部溃疡皮肤细胞重编程为iPS细胞（附原文）

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( J1 x1 b7 U* a& e( D+ {2016年8月13日/生物谷BIOON/--在一项新的研究中，来自美国塔夫茨大学和哈佛大学的研究人员成功地将来自糖尿病足部溃疡（diabetic foot ulcer）皮肤的成纤维细胞重编程为诱导性多能干细胞（iPS细胞）。这种重编程技术在效率上类似于利用来自非糖尿病病人的健康足部皮肤细胞经过重编程所产生的iPS细胞。这代表着人们在利用病人自己的细胞治疗难治愈性慢性创面（non-healing chronic wounds）---糖尿病的一种严重的并发症---方面取得重大进展。相关研究结果发表在2016年7月26日那期Cellular Reprogramming期刊上，论文标题为“Generation of Induced Pluripotent Stem Cells from Diabetic Foot Ulcer Fibroblasts Using a Nonintegrative Sendai Virus”。论文通信作者为来自塔夫茨大学牙医学院诊断科学系的Behzad Gerami-Naini博士。
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& J& J$ W, N, f/ o  q iPS细胞有潜力分化为许多种细胞类型，能够被用来构建疾病模型来研究新的治疗方法，如激活体内再生能力从而可能能够将非治愈性的成纤维细胞转化为再次获得修复功能的皮肤细胞。
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8 D: G- b6 ?3 o& W- v% k- n& B 在这项新的研究中，研究人员利用一种非整合性的仙台病毒将来自糖尿病足部溃疡皮肤的成纤维细胞系重编程为iPS细胞。他们描述了源自糖尿病足部溃疡皮肤的成纤维细胞在经过重编程后在未来的治疗潜力，这些细胞经过表观遗传重塑后可能能够逆转疾病过程。
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3 k" U) n9 v2 F% {- U5 ~8 z6 D. e Cellular Reprogramming期刊总编辑、英国医学研究理事会再生医学中心名誉教授Ian Wilmut爵士说，“这项研究提供两种新的方法来研究和治疗糖尿病足部溃疡。它揭示出用来治疗这种溃疡的一种新的细胞来源。此外，对来自糖尿病足部溃疡皮肤的成纤维细胞经重编程后产生的iPS细胞进行研究可能能够揭示出导致这种溃疡的分子变化。”（生物谷 Bioon.com）3 t" x3 K8 ?0 u% H0 g2 y$ u

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Generation of Induced Pluripotent Stem Cells from Diabetic Foot Ulcer Fibroblasts Using a Nonintegrative Sendai Virus1 ^6 j/ ]- @0 K- H+ k9 L8 y5 U" m

! }9 E, T. V9 a2 J% qBehzad Gerami-Naini, Avi Smith,1 Anna G. Maione,2 Olga Kashpur,1 Gianpaolo Carpinito,1 Aristides Veves,3 David J. Mooney,4 and Jonathan A. Garlick
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4 L7 P# A  C0 S3 x. Ddoi:10.1089/cell.2015.0087
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. S9 @' I) K* u: TDiabetic foot ulcers (DFUs) are nonhealing chronic wounds that are a serious complication of diabetes. Since induced pluripotent stem cells (iPSCs) may offer a potent source of autologous cells to heal these wounds, we studied if repair-deficient fibroblasts, derived from DFU patients and age- and site-matched control fibroblasts, could be reprogrammed to iPSCs. To establish this, we used Sendai virus to successfully reprogram six primary fibroblast cell lines derived from ulcerated skin of two DFU patients (DFU8, DFU25), nonulcerated foot skin from two diabetic patients (DFF24, DFF9), and healthy foot skin from two nondiabetic patients (NFF12, NFF14). We confirmed reprogramming to a pluripotent state through three independent criteria: immunofluorescent staining for SSEA-4 and TRA-1-81, formation of embryoid bodies with differentiation potential to all three embryonic germ layers in vitro, and formation of teratomas in vivo. All iPSC lines showed normal karyotypes and typical, nonmethylated CpG sites for OCT4 and NANOG. iPSCs derived from DFUs were similar to those derived from site-matched nonulcerated skin from both diabetic and nondiabetic patients. These results have established for the first time that multiple, DFU-derived fibroblast cell lines can be reprogrammed with efficiencies similar to control fibroblasts, thus demonstrating their utility for future regenerative therapy of DFUs.