Human-Induced Pluripotent Stem-Cell-Derived Smooth Muscle Cells Increase Angiogenesis to Treat Hindlimb Ischemia
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 previousl...
Ausführliche Beschreibung
Autor*in: |
Xixiang Gao [verfasserIn] Mingjie Gao [verfasserIn] Jolanta Gorecka [verfasserIn] John Langford [verfasserIn] Jia Liu [verfasserIn] Jiesi Luo [verfasserIn] Ryosuke Taniguchi [verfasserIn] Yutaka Matsubara [verfasserIn] Hao Liu [verfasserIn] Lianrui Guo [verfasserIn] Yongquan Gu [verfasserIn] Yibing Qyang [verfasserIn] Alan Dardik [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2021 |
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Übergeordnetes Werk: |
In: Cells - MDPI AG, 2012, 10(2021), 4, p 792 |
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Übergeordnetes Werk: |
volume:10 ; year:2021 ; number:4, p 792 |
Links: |
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DOI / URN: |
10.3390/cells10040792 |
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Katalog-ID: |
DOAJ015856054 |
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520 | |a 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, <i<p</i< < 0.05; Faber score, <i<p</i< < 0.05; flow, <i<p</i< = 0.054). hiPSC-SMC-treated mice showed fewer gastrocnemius fibers (<i<p</i< < 0.0001), increased fiber area (<i<p</i< < 0.0001), and enhanced capillary density (<i<p</i< < 0.01); microCT showed more arterioles (<96 μm). hiPSC-SMC treatment was associated with fewer numbers of macrophages, decreased numbers of M1-type (<i<p</i< < 0.05) and increased numbers of M2-type macrophages (<i<p</i< < 0.0001). Vascular endothelial growth factor (VEGF) expression in ischemic limbs was significantly elevated with hiPSC-SMC treatment (<i<p</i< < 0.05), and inhibition of VEGFR-2 with SU5416 was associated with fewer capillaries in hiPSC-SMC-treated limbs (<i<p</i< < 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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10.3390/cells10040792 doi (DE-627)DOAJ015856054 (DE-599)DOAJdc9d4a5ace584caaa8c932f8aa7110ff DE-627 ger DE-627 rakwb eng QH573-671 Xixiang Gao verfasserin aut Human-Induced Pluripotent Stem-Cell-Derived Smooth Muscle Cells Increase Angiogenesis to Treat Hindlimb Ischemia 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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, <i<p</i< < 0.05; Faber score, <i<p</i< < 0.05; flow, <i<p</i< = 0.054). hiPSC-SMC-treated mice showed fewer gastrocnemius fibers (<i<p</i< < 0.0001), increased fiber area (<i<p</i< < 0.0001), and enhanced capillary density (<i<p</i< < 0.01); microCT showed more arterioles (<96 μm). hiPSC-SMC treatment was associated with fewer numbers of macrophages, decreased numbers of M1-type (<i<p</i< < 0.05) and increased numbers of M2-type macrophages (<i<p</i< < 0.0001). Vascular endothelial growth factor (VEGF) expression in ischemic limbs was significantly elevated with hiPSC-SMC treatment (<i<p</i< < 0.05), and inhibition of VEGFR-2 with SU5416 was associated with fewer capillaries in hiPSC-SMC-treated limbs (<i<p</i< < 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. induced pluripotent stem cells smooth muscle cells angiogenesis peripheral artery disease chronic limb-threatening ischemia Cytology Mingjie Gao verfasserin aut Jolanta Gorecka verfasserin aut John Langford verfasserin aut Jia Liu verfasserin aut Jiesi Luo verfasserin aut Ryosuke Taniguchi verfasserin aut Yutaka Matsubara verfasserin aut Hao Liu verfasserin aut Lianrui Guo verfasserin aut Yongquan Gu verfasserin aut Yibing Qyang verfasserin aut Alan Dardik verfasserin aut In Cells MDPI AG, 2012 10(2021), 4, p 792 (DE-627)718622081 (DE-600)2661518-6 20734409 nnns volume:10 year:2021 number:4, p 792 https://doi.org/10.3390/cells10040792 kostenfrei https://doaj.org/article/dc9d4a5ace584caaa8c932f8aa7110ff kostenfrei https://www.mdpi.com/2073-4409/10/4/792 kostenfrei https://doaj.org/toc/2073-4409 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 4, p 792 |
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10.3390/cells10040792 doi (DE-627)DOAJ015856054 (DE-599)DOAJdc9d4a5ace584caaa8c932f8aa7110ff DE-627 ger DE-627 rakwb eng QH573-671 Xixiang Gao verfasserin aut Human-Induced Pluripotent Stem-Cell-Derived Smooth Muscle Cells Increase Angiogenesis to Treat Hindlimb Ischemia 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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, <i<p</i< < 0.05; Faber score, <i<p</i< < 0.05; flow, <i<p</i< = 0.054). hiPSC-SMC-treated mice showed fewer gastrocnemius fibers (<i<p</i< < 0.0001), increased fiber area (<i<p</i< < 0.0001), and enhanced capillary density (<i<p</i< < 0.01); microCT showed more arterioles (<96 μm). hiPSC-SMC treatment was associated with fewer numbers of macrophages, decreased numbers of M1-type (<i<p</i< < 0.05) and increased numbers of M2-type macrophages (<i<p</i< < 0.0001). Vascular endothelial growth factor (VEGF) expression in ischemic limbs was significantly elevated with hiPSC-SMC treatment (<i<p</i< < 0.05), and inhibition of VEGFR-2 with SU5416 was associated with fewer capillaries in hiPSC-SMC-treated limbs (<i<p</i< < 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. induced pluripotent stem cells smooth muscle cells angiogenesis peripheral artery disease chronic limb-threatening ischemia Cytology Mingjie Gao verfasserin aut Jolanta Gorecka verfasserin aut John Langford verfasserin aut Jia Liu verfasserin aut Jiesi Luo verfasserin aut Ryosuke Taniguchi verfasserin aut Yutaka Matsubara verfasserin aut Hao Liu verfasserin aut Lianrui Guo verfasserin aut Yongquan Gu verfasserin aut Yibing Qyang verfasserin aut Alan Dardik verfasserin aut In Cells MDPI AG, 2012 10(2021), 4, p 792 (DE-627)718622081 (DE-600)2661518-6 20734409 nnns volume:10 year:2021 number:4, p 792 https://doi.org/10.3390/cells10040792 kostenfrei https://doaj.org/article/dc9d4a5ace584caaa8c932f8aa7110ff kostenfrei https://www.mdpi.com/2073-4409/10/4/792 kostenfrei https://doaj.org/toc/2073-4409 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 4, p 792 |
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10.3390/cells10040792 doi (DE-627)DOAJ015856054 (DE-599)DOAJdc9d4a5ace584caaa8c932f8aa7110ff DE-627 ger DE-627 rakwb eng QH573-671 Xixiang Gao verfasserin aut Human-Induced Pluripotent Stem-Cell-Derived Smooth Muscle Cells Increase Angiogenesis to Treat Hindlimb Ischemia 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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, <i<p</i< < 0.05; Faber score, <i<p</i< < 0.05; flow, <i<p</i< = 0.054). hiPSC-SMC-treated mice showed fewer gastrocnemius fibers (<i<p</i< < 0.0001), increased fiber area (<i<p</i< < 0.0001), and enhanced capillary density (<i<p</i< < 0.01); microCT showed more arterioles (<96 μm). hiPSC-SMC treatment was associated with fewer numbers of macrophages, decreased numbers of M1-type (<i<p</i< < 0.05) and increased numbers of M2-type macrophages (<i<p</i< < 0.0001). Vascular endothelial growth factor (VEGF) expression in ischemic limbs was significantly elevated with hiPSC-SMC treatment (<i<p</i< < 0.05), and inhibition of VEGFR-2 with SU5416 was associated with fewer capillaries in hiPSC-SMC-treated limbs (<i<p</i< < 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. induced pluripotent stem cells smooth muscle cells angiogenesis peripheral artery disease chronic limb-threatening ischemia Cytology Mingjie Gao verfasserin aut Jolanta Gorecka verfasserin aut John Langford verfasserin aut Jia Liu verfasserin aut Jiesi Luo verfasserin aut Ryosuke Taniguchi verfasserin aut Yutaka Matsubara verfasserin aut Hao Liu verfasserin aut Lianrui Guo verfasserin aut Yongquan Gu verfasserin aut Yibing Qyang verfasserin aut Alan Dardik verfasserin aut In Cells MDPI AG, 2012 10(2021), 4, p 792 (DE-627)718622081 (DE-600)2661518-6 20734409 nnns volume:10 year:2021 number:4, p 792 https://doi.org/10.3390/cells10040792 kostenfrei https://doaj.org/article/dc9d4a5ace584caaa8c932f8aa7110ff kostenfrei https://www.mdpi.com/2073-4409/10/4/792 kostenfrei https://doaj.org/toc/2073-4409 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 4, p 792 |
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10.3390/cells10040792 doi (DE-627)DOAJ015856054 (DE-599)DOAJdc9d4a5ace584caaa8c932f8aa7110ff DE-627 ger DE-627 rakwb eng QH573-671 Xixiang Gao verfasserin aut Human-Induced Pluripotent Stem-Cell-Derived Smooth Muscle Cells Increase Angiogenesis to Treat Hindlimb Ischemia 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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, <i<p</i< < 0.05; Faber score, <i<p</i< < 0.05; flow, <i<p</i< = 0.054). hiPSC-SMC-treated mice showed fewer gastrocnemius fibers (<i<p</i< < 0.0001), increased fiber area (<i<p</i< < 0.0001), and enhanced capillary density (<i<p</i< < 0.01); microCT showed more arterioles (<96 μm). hiPSC-SMC treatment was associated with fewer numbers of macrophages, decreased numbers of M1-type (<i<p</i< < 0.05) and increased numbers of M2-type macrophages (<i<p</i< < 0.0001). Vascular endothelial growth factor (VEGF) expression in ischemic limbs was significantly elevated with hiPSC-SMC treatment (<i<p</i< < 0.05), and inhibition of VEGFR-2 with SU5416 was associated with fewer capillaries in hiPSC-SMC-treated limbs (<i<p</i< < 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. induced pluripotent stem cells smooth muscle cells angiogenesis peripheral artery disease chronic limb-threatening ischemia Cytology Mingjie Gao verfasserin aut Jolanta Gorecka verfasserin aut John Langford verfasserin aut Jia Liu verfasserin aut Jiesi Luo verfasserin aut Ryosuke Taniguchi verfasserin aut Yutaka Matsubara verfasserin aut Hao Liu verfasserin aut Lianrui Guo verfasserin aut Yongquan Gu verfasserin aut Yibing Qyang verfasserin aut Alan Dardik verfasserin aut In Cells MDPI AG, 2012 10(2021), 4, p 792 (DE-627)718622081 (DE-600)2661518-6 20734409 nnns volume:10 year:2021 number:4, p 792 https://doi.org/10.3390/cells10040792 kostenfrei https://doaj.org/article/dc9d4a5ace584caaa8c932f8aa7110ff kostenfrei https://www.mdpi.com/2073-4409/10/4/792 kostenfrei https://doaj.org/toc/2073-4409 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 4, p 792 |
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Xixiang Gao Mingjie Gao Jolanta Gorecka John Langford Jia Liu Jiesi Luo Ryosuke Taniguchi Yutaka Matsubara Hao Liu Lianrui Guo Yongquan Gu Yibing Qyang Alan Dardik |
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human-induced pluripotent stem-cell-derived smooth muscle cells increase angiogenesis to treat hindlimb ischemia |
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Human-Induced Pluripotent Stem-Cell-Derived Smooth Muscle Cells Increase Angiogenesis to Treat Hindlimb Ischemia |
abstract |
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, <i<p</i< < 0.05; Faber score, <i<p</i< < 0.05; flow, <i<p</i< = 0.054). hiPSC-SMC-treated mice showed fewer gastrocnemius fibers (<i<p</i< < 0.0001), increased fiber area (<i<p</i< < 0.0001), and enhanced capillary density (<i<p</i< < 0.01); microCT showed more arterioles (<96 μm). hiPSC-SMC treatment was associated with fewer numbers of macrophages, decreased numbers of M1-type (<i<p</i< < 0.05) and increased numbers of M2-type macrophages (<i<p</i< < 0.0001). Vascular endothelial growth factor (VEGF) expression in ischemic limbs was significantly elevated with hiPSC-SMC treatment (<i<p</i< < 0.05), and inhibition of VEGFR-2 with SU5416 was associated with fewer capillaries in hiPSC-SMC-treated limbs (<i<p</i< < 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. |
abstractGer |
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, <i<p</i< < 0.05; Faber score, <i<p</i< < 0.05; flow, <i<p</i< = 0.054). hiPSC-SMC-treated mice showed fewer gastrocnemius fibers (<i<p</i< < 0.0001), increased fiber area (<i<p</i< < 0.0001), and enhanced capillary density (<i<p</i< < 0.01); microCT showed more arterioles (<96 μm). hiPSC-SMC treatment was associated with fewer numbers of macrophages, decreased numbers of M1-type (<i<p</i< < 0.05) and increased numbers of M2-type macrophages (<i<p</i< < 0.0001). Vascular endothelial growth factor (VEGF) expression in ischemic limbs was significantly elevated with hiPSC-SMC treatment (<i<p</i< < 0.05), and inhibition of VEGFR-2 with SU5416 was associated with fewer capillaries in hiPSC-SMC-treated limbs (<i<p</i< < 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. |
abstract_unstemmed |
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, <i<p</i< < 0.05; Faber score, <i<p</i< < 0.05; flow, <i<p</i< = 0.054). hiPSC-SMC-treated mice showed fewer gastrocnemius fibers (<i<p</i< < 0.0001), increased fiber area (<i<p</i< < 0.0001), and enhanced capillary density (<i<p</i< < 0.01); microCT showed more arterioles (<96 μm). hiPSC-SMC treatment was associated with fewer numbers of macrophages, decreased numbers of M1-type (<i<p</i< < 0.05) and increased numbers of M2-type macrophages (<i<p</i< < 0.0001). Vascular endothelial growth factor (VEGF) expression in ischemic limbs was significantly elevated with hiPSC-SMC treatment (<i<p</i< < 0.05), and inhibition of VEGFR-2 with SU5416 was associated with fewer capillaries in hiPSC-SMC-treated limbs (<i<p</i< < 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. |
collection_details |
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Human-Induced Pluripotent Stem-Cell-Derived Smooth Muscle Cells Increase Angiogenesis to Treat Hindlimb Ischemia |
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https://doi.org/10.3390/cells10040792 https://doaj.org/article/dc9d4a5ace584caaa8c932f8aa7110ff https://www.mdpi.com/2073-4409/10/4/792 https://doaj.org/toc/2073-4409 |
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