Nestin(+) Tissue-Resident Multipotent Stem Cells Contribute to Tumor Progression by Differentiating into Pericytes and Smooth Muscle Cells Resulting in Blood Vessel Remodeling

Vascular applications in regenerative medicine include blood vessel substitutes and vasculogenesis in ischemic or engineered tissues. For these repair processes to be successful, there is a need for a stable supply of endothelial and smooth muscle cells. For blood vessel substitutes, the immediate goal is to enable blood flow, but vasoactivity is necessary for long term success. In engineered vessels, it is thought that endothelial cells will serve as an anti-thrombogenic lumenal layer, while smooth muscle cells contribute to vessel contractility. In other clinical applications, what is needed is not a vessel substitute but the promotion of new vessel formation (vasculogenesis). A simplified account of vasculogenesis is that endothelial cells assemble to form vessel-like structures that can then be stabilized by smooth muscle cells. Overall, the need for new vasculature to transfer oxygen and nutrients is important to reperfuse not only ischemic tissue in vivo, but also dense, structurally complex engineered tissue. The impact of these vascular therapies, however, is limited in part by the low yield and inadequate in vitro proliferation potential of primary endothelial and smooth muscle cells. Thus, there is a need to address the cell sourcing issue for vascular cell-based therapies, potentially using stem cells.

Download Full-text

Vascular Smooth Muscle Cells (VSMCs) in Blood Vessel Tissue Engineering: The Use of Differentiated Cells or Stem Cells as VSMC Precursors

Muscle Cell and Tissue - Current Status of Research Field ◽

10.5772/intechopen.77108 ◽

2018 ◽

Cited By ~ 1

Author(s):

Lucie Bacakova ◽

Martina Travnickova ◽

Elena Filova ◽

Roman Matejka ◽

Jana Stepanovska ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Smooth Muscle ◽

Blood Vessel ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Vascular Smooth Muscle Cells ◽

Muscle Cells ◽

Differentiated Cells

Download Full-text

Vascular Wall-Resident CD44+ Multipotent Stem Cells Give Rise to Pericytes and Smooth Muscle Cells and Contribute to New Vessel Maturation

PLoS ONE ◽

10.1371/journal.pone.0020540 ◽

2011 ◽

Vol 6 (5) ◽

pp. e20540 ◽

Cited By ~ 102

Author(s):

Diana Klein ◽

Philip Weißhardt ◽

Veronika Kleff ◽

Holger Jastrow ◽

Heinz Günther Jakob ◽

...

Keyword(s):

Stem Cells ◽

Smooth Muscle ◽

Smooth Muscle Cells ◽

Muscle Cells ◽

Vascular Wall ◽

Multipotent Stem Cells ◽

Vessel Maturation

Download Full-text

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

Cells ◽

10.3390/cells10040792 ◽

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.

Download Full-text