Coadministration of endothelial and smooth muscle cells derived from human induced pluripotent stem cells as a therapy for critical limb ischemia

Autor: Yang Woo Kwon, Chang-Seok Kim, Sang Mo Kwon, Da Sol Kim, Kinarm Ko, Sun Sik Bae, Jeong-Won Kim, Gyu Tae Park, Ye Seul Kim, Jin Ju Park, Jung Won Yoon, Jae Ho Kim
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Chronic Limb-Threatening Ischemia
Vascular smooth muscle
Angiogenesis
induced pluripotent stem cells
Myocytes
Smooth Muscle
CD34
Antigens
CD34
Manufacturing for Regenerative Medicine
03 medical and health sciences
Mice
Peripheral Arterial Disease
0302 clinical medicine
Medicine
Animals
Humans
Therapeutic angiogenesis
Progenitor cell
lcsh:QH573-671
Induced pluripotent stem cell
Cells
Cultured
lcsh:R5-920
peripheral artery diseases
business.industry
lcsh:Cytology
Cell Differentiation
Cell Biology
General Medicine
differentiation
musculoskeletal system
endothelial cells
Cell biology
smooth muscle cells
Transplantation
030104 developmental biology
Culture Media
Conditioned
cardiovascular system
Stem cell
business
lcsh:Medicine (General)
030217 neurology & neurosurgery
Developmental Biology
Zdroj: Stem Cells Translational Medicine, Vol 10, Iss 3, Pp 414-426 (2021)
Stem Cells Translational Medicine
ISSN: 2157-6564
2157-6580
Popis: Critical limb ischemia is a condition in which tissue necrosis occurs due to arterial occlusion, resulting in limb amputation in severe cases. Both endothelial cells (ECs) and vascular smooth muscle cells (SMCs) are needed for the regeneration of peripheral arteries in ischemic tissues. However, it is difficult to isolate and cultivate primary EC and SMC from patients for therapeutic angiogenesis. Induced pluripotent stem cells (iPSCs) are regarded as useful stem cells due to their pluripotent differentiation potential. In this study, we explored the therapeutic efficacy of human iPSC‐derived EC and iPSC‐derived SMC in peripheral artery disease model. After the induction of mesodermal differentiation of iPSC, CD34+ progenitor cells were isolated by magnetic‐activated cell sorting. Cultivation of the CD34+ progenitor cells in endothelial culture medium induced the expression of endothelial markers and phenotypes. Moreover, the CD34+ cells could be differentiated into SMC by cultivation in SMC culture medium. In a murine hindlimb ischemia model, cotransplantation of EC with SMC improved blood perfusion and increased the limb salvage rate in ischemic limbs compared to transplantation of either EC or SMC alone. Moreover, cotransplantation of EC and SMC stimulated angiogenesis and led to the formation of capillaries and arteries/arterioles in vivo. Conditioned medium derived from SMC stimulated the migration, proliferation, and tubulation of EC in vitro, and these effects were recapitulated by exosomes isolated from the SMC‐conditioned medium. Together, these results suggest that iPSC‐derived SMC enhance the therapeutic efficacy of iPSC‐derived EC in peripheral artery disease via an exosome‐mediated paracrine mechanism.
Co‐transplantation of the induced pluripotent stem cell (iPSC)‐derived endothelial cells and smooth muscle cells enhanced the therapeutic efficacies of endothelial cells and smooth muscle cells in a murine hindlimb ischemia model. Smooth muscle cells promoted angiogenesis and therapy of peripheral artery disease through exosome‐mediated paracrin mechanism.
Databáze: OpenAIRE
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