scholarly journals Human-Induced Pluripotent Stem-Cell-Derived Smooth Muscle Cells Increase Angiogenesis to Treat Hindlimb Ischemia

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 792
Author(s):  
Xixiang Gao ◽  
Mingjie Gao ◽  
Jolanta Gorecka ◽  
John Langford ◽  
Jia Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Smooth Muscle ◽  
Stem Cell ◽  
Smooth Muscle Cells ◽  
Functional Outcomes ◽  
Ethical Issues ◽  
Muscle Cells ◽  
Doppler Imaging ◽  
Hindlimb Ischemia ◽  
Induced Pluripotent

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.

scholarly journals Induced pluripotent stem cell-derived vascular smooth muscle cells: methods and application

2015 ◽  
Vol 465 (2) ◽  
pp. 185-194 ◽  
Author(s):  
Biraja C. Dash ◽  
Zhengxin Jiang ◽  
Carol Suh ◽  
Yibing Qyang
Keyword(s):  
Smooth Muscle ◽  
Stem Cell ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Muscle Cells ◽  
Regenerative Therapy ◽  
Induced Pluripotent

Vascular smooth muscle cells (VSMCs) play a major role in the pathophysiology of cardiovascular diseases. The advent of induced pluripotent stem cell (iPSC) technology and the capability of differentiating into virtually every cell type in the human body make this field a ray of hope for vascular regenerative therapy and understanding of the disease mechanism. In the present review, we first discuss the recent iPSC technology and vascular smooth muscle development from an embryo and then examine different methodologies to derive VSMCs from iPSCs, and their applications in regenerative therapy and disease modelling.

Abstract 13982: Derivation of Functional Smooth Muscle Cells From Integration-free Induced Pluripotent Stem Cells Through Cardiovascular Progenitor Cell Intermediates for Vascular Regeneration

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Yongyu Wang ◽  
Jiang Hu ◽  
Jiao jiao ◽  
Zhou Zhou ◽  
Eugene Y Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Progenitor Cell ◽  
Muscle Cells ◽  
Vascular Regeneration ◽  
Induced Pluripotent

Tissue-engineered blood vessels (TEBVs) hold great promise for replacement of damaged or defective vascular tissues in vascular disease therapies, such as coronary and peripheral bypass graft surgeries. However, it remains a great challenge to obtain sufficient numbers of functional smooth muscle cells (SMCs) in the practice of constructing patient-specific TEBVs. This study aimed to develop an efficient method to generate a large number of functional SMCs in a short term for constructing tissue-engineered vascular tissues. Human induced pluripotent stem cells (iPSCs) were established by integration-free episomal vector-based reprogramming of donor peripheral blood mononuclear cells (PBMCs). These established iPSCs expressed pluripotency markers and were demonstrated to be able to differentiate into all three germ layer cells. Cardiovascular progenitor cell (CVPC) intermediates were then promptly and efficiently induced and expanded in chemically defined medium. Vascular smooth muscle cells (SMCs) were further induced under differentiation condition, which expressed typical SMCs markers including smooth muscle α-actin (α-SMA), calponin and SM22α validated by quantitative real-time PCR and immunocytochemistry stain. Importantly, the derived SMCs showed functional properties, validated by contraction responsiveness to carbachol treatment, up-regulation of specific collagens gene expression under transforming growth factor β1 treatment and up-regulation of specific matrix metalloproteinases gene expression under cytokine stimuli. Future studies will be focused on using these functional SMCs to construct functional TEBVs on biomimetic scaffolds. Taken together, our study established a facile procedure to generate large amount of functional and safe SMCs for vascular regeneration, via establishment of donor-specific integration-free human iPSCs and directed differentiation through CVPC intermediates.

scholarly journals A Comparison of Murine Smooth Muscle Cells Generated from Embryonic versus Induced Pluripotent Stem Cells

2009 ◽  
Vol 18 (5) ◽  
pp. 741-748 ◽  
Author(s):  
Chang-Qing Xie ◽  
Huarong Huang ◽  
Sheng Wei ◽  
Long-Sheng Song ◽  
Jifeng Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Muscle Cells ◽  
Induced Pluripotent
Sign in / Sign up

Export Citation Format

Share Document