scholarly journals Arterial Sca1+ Vascular Stem Cells Generate De Novo Smooth Muscle for Artery Repair and Regeneration

2020 ◽  
Vol 26 (1) ◽  
pp. 81-96.e4 ◽  
Author(s):  
Juan Tang ◽  
Haixiao Wang ◽  
Xiuzhen Huang ◽  
Fei Li ◽  
Huan Zhu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Smooth Muscle ◽  
De Novo ◽  
Vascular Stem Cells

Abstract 143: Enrichment of Dimethylation of Lysine 4 on Histone 3 and Resident Vascular Stem Cell Transition to Vascular Smooth Muscle Cells

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Roya Hakimjavadi ◽  
Denise Burtenshaw ◽  
Emma Fitzpatrick ◽  
Mariana Di Luca ◽  
Gillian Casey ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Smooth Muscle ◽  
Stem Cell ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Telomerase Activity ◽  
Histone 3 ◽  
Vascular Stem Cells

Data support a role for stem cell-derived vascular smooth muscle cells (SMC) in arteriosclerosis. Epigenetics play a critical role in SMC differentiation where histone proteins associated with the myosin heavy chain (Myh11) promoter are post-translationally modified by dimethylation of lysine 4 on histone 3 (H3K4me2). Studies report that ‘de-differentiated’ SMC do not exhibit loss of H3K4me2 at the Myh11 promoter even when mRNA levels decrease thereby allowing this modification to be used to track differentiated SMC. Our aim was to determine the level of H3K4me2 and H3K27me3 methylation of differentiated SMCs and compare to resident vascular stem cells and stem cell-derived SMC. Murine adventitial Sca1 + stem cells (APCs), rat medial Sox10 + multipotent vascular stem cells (MVSCs) and CD44 + bone-marrow derived mesenchymal stem cells (MSCs) were all examined for methylation of lysine 4 (H3K4me2) and lysine 27 (H3K27me3) on histone 3 associated with the Myh11 promoter, before and after SMC differentiation and compared to fresh aortic differentiated SMC and sub-cultured de-differentiated SMC in vitro by Chromatin Immunoprecipitation (ChIP) assay. Cells were also examined for Myh11 expression, stemness (telomerase activity) and multipotentcy. Differentiated rat and murine SMC were enriched for H3K4Me2 at the Myh11 promoter, compared to H3K27me3. Phenotypically de-differentiated sub-cutured rat and murine SMC were enriched for H3K4Me2 when compared to H3K27me3, but to a much lesser extent when compared to differentiated aortic SMC. In contrast, resident APCs and MVSCs, and bone-marrow derived MSCs, were all enriched for H3K27me3, concomitant with significant telomerase activity and multipotent differentiation capacity. The levels of enrichment of H3K27me3 dropped significantly after SMC differentiation with TGF-βeta1 concomitant with a significant enrichment of H3K4me2 to levels that mimicked the level of enrichment in de-differentiated SMC when compared to aortic differentiated SMC. De-differentiated SMC exhibit reduced enrichment of H3K4me2 at the Myh11 promoter region when compared to differentiated aortic SMCs, but mimic the level of enrichment of H3K4me2 observed following resident vascular stem cell differentiation to SMCs.

scholarly journals Oxidation Prevents HMGB1 Inhibition on PDGF-Induced Differentiation of Multipotent Vascular Stem Cells to Smooth Muscle Cells: A Possible Mechanism Linking Oxidative Stress to Atherosclerosis

2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Xiaohu Meng ◽  
Wenjie Su ◽  
Xuan Tao ◽  
Mingyang Sun ◽  
Rongchao Ying ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Neointimal Hyperplasia ◽  
High Mobility ◽  
Muscle Cells ◽  
Oxidative Modification ◽  
Vascular Stem Cells ◽  
Multipotent Vascular Stem Cells

Atherosclerosis is considered as a multifactorial disease in terms of the pathogenic mechanisms. Oxidative stress has been implicated in atherogenesis, and the putative mechanisms of its action include oxidative modification of redox-sensitive signaling factors. High mobility group box 1 (HMGB1) is a key inflammatory mediator in atherosclerosis, but if oxidized it loses its activity. Thus, whether and how it participates in oxidative stress-induced atherosclerosis are not clear. The current study found that exogenous HMGB1 dose-dependently inhibited the proliferation of multipotent vascular stem cells and their differentiation to smooth muscle cells induced by platelet-derived growth factor. But oxidative modification impaired the activity of HMGB1 to produce the effect. The stem cells were regarded as the source of smooth muscle cells in vascular remodeling and neointimal hyperplasia. Therefore, the findings suggested that HMGB1 participated in oxidative stress-induced atherosclerosis presumably by targeting multipotent vascular stem cells.

scholarly journals Embryonic rat vascular smooth muscle cells revisited - a model for neonatal, neointimal SMC or differentiated vascular stem cells?

Vascular Cell ◽  
2014 ◽  
Vol 6 (1) ◽  
pp. 6 ◽  
Author(s):  
Eimear Kennedy ◽  
Roya Hakimjavadi ◽  
Chris Greene ◽  
Ciaran J Mooney ◽  
Emma Fitzpatrick ◽  
...  
Keyword(s):  
Stem Cells ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Vascular Stem Cells

scholarly journals The calcium binding protein S100β marks hedgehog-responsive resident vascular stem cells within vascular lesions

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Mariana Di Luca ◽  
Emma Fitzpatrick ◽  
Denise Burtenshaw ◽  
Weimin Liu ◽  
Jay-Christian Helt ◽  
...  
Keyword(s):  
Stem Cells ◽  
Smooth Muscle ◽  
Myogenic Differentiation ◽  
Lineage Tracing ◽  
Epigenetic Mark ◽  
Genetic Lineage ◽  
Lesion Formation ◽  
Hedgehog Signalling ◽  
Vascular Stem Cells

AbstractA hallmark of subclinical atherosclerosis is the accumulation of vascular smooth muscle cell (SMC)-like cells leading to intimal thickening. While medial SMCs contribute, the participation of hedgehog-responsive resident vascular stem cells (vSCs) to lesion formation remains unclear. Using transgenic eGFP mice and genetic lineage tracing of S100β vSCs in vivo, we identified S100β/Sca1 cells derived from a S100β non-SMC parent population within lesions that co-localise with smooth muscle α-actin (SMA) cells following iatrogenic flow restriction, an effect attenuated following hedgehog inhibition with the smoothened inhibitor, cyclopamine. In vitro, S100β/Sca1 cells isolated from atheroprone regions of the mouse aorta expressed hedgehog signalling components, acquired the di-methylation of histone 3 lysine 4 (H3K4me2) stable SMC epigenetic mark at the Myh11 locus and underwent myogenic differentiation in response to recombinant sonic hedgehog (SHh). Both S100β and PTCH1 cells were present in human vessels while S100β cells were enriched in arteriosclerotic lesions. Recombinant SHh promoted myogenic differentiation of human induced pluripotent stem cell-derived S100β neuroectoderm progenitors in vitro. We conclude that hedgehog-responsive S100β vSCs contribute to lesion formation and support targeting hedgehog signalling to treat subclinical arteriosclerosis.

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 Vascular stem cells—potential for clinical application

2016 ◽  
Vol 118 (1) ◽  
pp. 127-137 ◽  
Author(s):  
Sadie C. Slater ◽  
Michele Carrabba ◽  
Paolo Madeddu
Keyword(s):  
Stem Cells ◽  
Clinical Application ◽  
Vascular Stem Cells
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