Quality-Quantity Control Culture Enhances Vasculogenesis and Wound Healing Efficacy of Human Diabetic Peripheral Blood CD34+ Cells.
Quality-Quantity Control Culture Enhances Vasculogenesis and Wound Healing Efficacy of Human Diabetic Peripheral Blood CD34+ Cells.
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DOI：
10.1002/sctm.17-0043
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发表时间：
2018-05
影响因子：
6
通讯作者：
Asahara T
中科院分区：
文献类型：
--
作者：
Tanaka R;Masuda H;Fujimura S;Ito-Hirano R;Arita K;Kakinuma Y;Hagiwara H;Kado M;Hayashi A;Mita T;Ogawa T;Watada H;Mizuno H;Sawada N;Asahara T
自体内皮祖细胞（EPC）疗法通常用于刺激缺血修复和伤口愈合中的血管生成。然而，EPCs的低总数和功能缺陷使得自体EPC治疗在糖尿病中无效。目前，没有已知的离体培养技术可以扩增和/或改善临床使用的EPC的功能缺陷。最近，我们发现质量-数量培养（QQc）系统恢复了小鼠糖尿病EPCs的血管生成和伤口愈合功效。为了验证这些结果并阐明转化研究中的机制，我们评估了该QQc系统恢复糖尿病人外周血（PB）CD 34+细胞血管生成潜力的功效。对从糖尿病患者和健康患者的PB纯化的CD 34+细胞进行QQc。基因表达，血管再生，细胞因子和旁分泌介质的表达进行了分析。将QQc前或后糖尿病人PB-CD 34+细胞移植到受伤的BALB/c裸鼠和链脲佐菌素诱导的糖尿病小鼠中，以评估功能疗效。QQc后糖尿病人PB‐ CD 34+细胞治疗显著加速伤口闭合、上皮再形成和血管生成。QQc后糖尿病人PB-CD 34+细胞的治疗效果更高，这归因于糖尿病CD 34+细胞的分化能力增强、直接血管生成以及血管生成因子和伤口愈合基因的表达增强。因此，QQc可以显著增强人PB-CD 34+细胞在糖尿病伤口中的治疗功效，克服糖尿病患者中自体细胞治疗的固有局限性，并且不仅可用于治疗伤口，还可用于治疗其他缺血性疾病。干细胞转化医学2018;7：428-438
Autologous endothelial progenitor cell (EPC) therapy is commonly used to stimulate angiogenesis in ischemic repair and wound healing. However, low total numbers and functional deficits of EPCs make autologous EPC therapy ineffective in diabetes. Currently, no known ex vivo culture techniques can expand and/or ameliorate the functional deficits of EPCs for clinical usage. Recently, we showed that a quality‐quantity culture (QQc) system restores the vasculogenic and wound‐healing efficacy of murine diabetic EPCs. To validate these results and elucidate the mechanism in a translational study, we evaluated the efficacy of this QQc system to restore the vasculogenic potential of diabetic human peripheral blood (PB) CD34+ cells. CD34+ cells purified from PB of diabetic and healthy patients were subjected to QQc. Gene expression, vascular regeneration, and expression of cytokines and paracrine mediators were analyzed. Pre‐ or post‐QQc diabetic human PB‐CD34+ cells were transplanted into wounded BALB/c nude mice and streptozotocin‐induced diabetic mice to assess functional efficacy. Post‐QQc diabetic human PB‐CD34+ cell therapy significantly accelerated wound closure, re‐epithelialization, and angiogenesis. The higher therapeutic efficacy of post‐QQc diabetic human PB‐CD34+ cells was attributed to increased differentiation ability of diabetic CD34+ cells, direct vasculogenesis, and enhanced expression of angiogenic factors and wound‐healing genes. Thus, QQc can significantly enhance the therapeutic efficacy of human PB‐CD34+ cells in diabetic wounds, overcoming the inherent limitation of autologous cell therapy in diabetic patients, and could be useful for treatment of not only wounds but also other ischemic diseases. Stem Cells Translational Medicine 2018;7:428–438
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影响因子：
37.8
作者：
Ii M;Takeshita K;Ibusuki K;Luedemann C;Wecker A;Eaton E;Thorne T;Asahara T;Liao JK;Losordo DW
通讯作者：
Losordo DW
影响因子：
29
作者：
Sawada N;Jiang A;Takizawa F;Safdar A;Manika A;Tesmenitsky Y;Kang KT;Bischoff J;Kalwa H;Sartoretto JL;Kamei Y;Benjamin LE;Watada H;Ogawa Y;Higashikuni Y;Kessinger CW;Jaffer FA;Michel T;Sata M;Croce K;Tanaka R;Arany Z
通讯作者：
Arany Z
影响因子：
56.9
作者：
Asahara, T;Murohara, T;Isner, JM
通讯作者：
Isner, JM
硫化氢通过恢复内皮祖细胞功能和激活 2 型糖尿病患者的血管生成素-1 来改善伤口愈合
影响因子：
7.7
作者：
Liu F;Chen DD;Sun X;Xie HH;Yuan H;Jia W;Chen AF
通讯作者：
Chen AF
影响因子：
37.8
作者：
Hofmann, M;Wollert, KC;Drexler, H
通讯作者：
Drexler, H