Human-Induced Pluripotent Stem-Cell-Derived Smooth Muscle Cells Increase Angiogenesis to Treat Hindlimb Ischemia.
Human-Induced Pluripotent Stem-Cell-Derived Smooth Muscle Cells Increase Angiogenesis to Treat Hindlimb Ischemia.
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DOI：
10.3390/cells10040792
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发表时间：
2021-04-02
期刊：
影响因子：
6
通讯作者：
Dardik A
中科院分区：
文献类型：
--
作者：
Gao X;Gao M;Gorecka J;Langford J;Liu J;Luo J;Taniguchi R;Matsubara Y;Liu H;Guo L;Gu Y;Qyang Y;Dardik A
诱导多能干细胞（iPSC）是一种创新的、来源于体细胞的、容易获得的、可再生的干细胞来源，没有相当大的伦理问题。与其他干细胞相比，iPSC及其衍生细胞可能具有更强的治疗和转化潜力。我们之前的研究表明，人类ipsc来源的平滑肌细胞（hiPSC-SMC）促进血管生成和伤口愈合。因此，我们假设hiPSC-SMC可能是没有标准治疗选择的人类慢性肢体威胁缺血患者的一种新治疗方法。我们在小鼠后肢缺血模型中测定了hiPSC-SMC的血管生成潜能。裸鼠后肢缺血后肌内注射hiPSC-SMC。采用标准化评分、激光多普勒成像、显微ct、组织学和免疫荧光测量功能结局和灌注。与对照组相比，hipsc - smc治疗小鼠的功能结局和血流得到改善（Tarlov评分，p < 0.05； Faber评分，p < 0.05；血流，p = 0.054）。hipsc - smc处理小鼠腓肠肌纤维减少（p < 0.0001），纤维面积增加（p < 0.0001），毛细血管密度增加（p < 0.01）；微ct显示<96 μm的微动脉较多。hiPSC-SMC治疗与巨噬细胞数量减少，m1型巨噬细胞数量减少（p < 0.05）， m2型巨噬细胞数量增加（p < 0.0001）相关。血管内皮生长因子（VEGF）在缺血肢体中的表达在hiPSC-SMC治疗组显著升高（p < 0.05）， SU5416抑制VEGFR-2与hiPSC-SMC治疗肢体中毛细血管减少相关（p < 0.0001）。hiPSC-SMC促进vegf介导的血管生成，改善后肢缺血。利用ipsc衍生细胞进行干细胞治疗可能是一种新的、潜在的可翻译的肢体缺血治疗方法。
Induced pluripotent stem cells (iPSC) represent an innovative, somatic cell-derived, easily obtained and renewable stem cell source without considerable ethical issues. iPSC and their derived cells may have enhanced therapeutic and translational potential compared with other stem cells. We previously showed that human iPSC-derived smooth muscle cells (hiPSC-SMC) promote angiogenesis and wound healing. Accordingly, we hypothesized that hiPSC-SMC may be a novel treatment for human patients with chronic limb-threatening ischemia who have no standard options for therapy. We determined the angiogenic potential of hiPSC-SMC in a murine hindlimb ischemia model. hiPSC-SMC were injected intramuscularly into nude mice after creation of hindlimb ischemia. Functional outcomes and perfusion were measured using standardized scores, laser Doppler imaging, microCT, histology and immunofluorescence. Functional outcomes and blood flow were improved in hiPSC-SMC-treated mice compared with controls (Tarlov score, p < 0.05; Faber score, p < 0.05; flow, p = 0.054). hiPSC-SMC-treated mice showed fewer gastrocnemius fibers (p < 0.0001), increased fiber area (p < 0.0001), and enhanced capillary density (p < 0.01); microCT showed more arterioles (<96 μm). hiPSC-SMC treatment was associated with fewer numbers of macrophages, decreased numbers of M1-type (p < 0.05) and increased numbers of M2-type macrophages (p < 0.0001). Vascular endothelial growth factor (VEGF) expression in ischemic limbs was significantly elevated with hiPSC-SMC treatment (p < 0.05), and inhibition of VEGFR-2 with SU5416 was associated with fewer capillaries in hiPSC-SMC-treated limbs (p < 0.0001). hiPSC-SMC promote VEGF-mediated angiogenesis, leading to improved hindlimb ischemia. Stem cell therapy using iPSC-derived cells may represent a novel and potentially translatable therapy for limb-threatening ischemia.
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影响因子：
168.9
作者：
Fowkes, F. Gerald R.;Rudan, Diana;Criqui, Michael H.
通讯作者：
Criqui, Michael H.
影响因子：
20.1
作者：
Aicher, Alexandra;Rentsch, Markus;Heeschen, Christopher
通讯作者：
Heeschen, Christopher
DOI：
10.1007/s00018-017-2730-7
发表时间：
2018-04
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Klein D
通讯作者：
Klein D
影响因子：
37.8
作者：
Ganta VC;Choi MH;Kutateladze A;Fox TE;Farber CR;Annex BH
通讯作者：
Annex BH
DOI：
10.1111/j.1742-1241.2011.02886.x
发表时间：
2012-04-01
影响因子：
2.6
作者：
Kirana, S.;Stratmann, B.;Tschoepe, D.
通讯作者：
Tschoepe, D.