scholarly journals Induced pluripotent stem cell-derived smooth muscle cells increase angiogenesis and accelerate diabetic wound healing

2020 ◽  
Vol 15 (2) ◽  
pp. 1277-1293 ◽  
Author(s):  
Jolanta Gorecka ◽  
Xixiang Gao ◽  
Arash Fereydooni ◽  
Biraja C Dash ◽  
Jiesi Luo ◽  
...  

Aim: To assess the potential of human induced pluripotent stem cell-derived smooth muscle cells (hiPSC-SMC) to accelerate diabetic wound healing. Methods: hiPSC-SMC were embedded in 3D collagen scaffolds and cultured in vitro for 72 h; scaffolds were then applied to diabetic, nude mouse, splinted back wounds to assess in vivo healing. Cultured medium after scaffold incubation was collected and analyzed for expression of pro-angiogenic cytokines. Results: hiPSC-SMC secrete increased concentration of pro-angiogenic cytokines, compared with murine adipose derived stem cells. Delivery of hiPSC-SMC-containing collagen scaffolds accelerates diabetic wound healing and is associated with an increased number of total and M2 type macrophages. Conclusion: hiPSC-SMC promote angiogenesis and accelerate diabetic wound healing, making them a promising new candidate for treatment of diabetic wounds.

2020 ◽  
Vol 9 (16) ◽  
pp. 2070051
Author(s):  
Francesco Santarella ◽  
Rukmani Sridharan ◽  
Milica Marinkovic ◽  
Ronaldo Jose Farias Correa Do Amaral ◽  
Brenton Cavanagh ◽  
...  

2020 ◽  
Vol 9 (16) ◽  
pp. 2000307
Author(s):  
Francesco Santarella ◽  
Rukmani Sridharan ◽  
Milica Marinkovic ◽  
Ronaldo Jose Farias Correa Do Amaral ◽  
Brenton Cavanagh ◽  
...  

2021 ◽  
Author(s):  
Biraja C. Dash ◽  
Kaiti Duan ◽  
Themis Kyriakides ◽  
Henry Hsia

Human-induced pluripotent stem cell-derived-vascular smooth muscle cells (hiPSC-VSMC) and their secretome have been shown to promote angiogenesis and wound healing. However, there is a paucity of research on how the...


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Albert J Pedroza ◽  
Samantha Churovich ◽  
Nobu Yokoyama ◽  
Ken Nakamura ◽  
Cristiana Iosef Husted ◽  
...  

Introduction: Mutations in TGF-beta (TGF-ß) signaling genes lead to aortic root aneurysm in Loeys Dietz syndrome (LDS). Smooth muscle cells (SMCs) in the proximal aorta develop from two embryologic origins: second heart field (SHF) and neural crest (NC). Induced pluripotent stem cell (iPSC) models simulate these lineages, but direct correlation to clinical disease is lacking. Hypothesis: iPSC-derived SMCs accurately model lineage-specific aortopathy in LDS. Methods: We generated SMC lines from root and ascending aortic surgical tissue and iPSC-derived SMCs through SHF and NC-specific pathways from an LDS patient ( TGFBR1 mutation). Lineage-specific TGF-ß responses were determined by western blot/ELISA. RNA sequencing and RT-PCR identified SMC transcriptomes. Results: Aortic root SMCs showed greater canonical TGF-ß activation (p-SMAD2/3) versus ascending at baseline and with TGF-ß stimulation ( Figure ). Synonymous results were seen in SHF versus NC SMCs from the iPSC pathway. RNAseq identified 1,600 differentially expressed genes between iPSC lineages, including altered TGF-ß receptor and ligand expression profiles. Primary aortic lines validated iPSC data: root SMCs showed enriched TGF-ß receptor 1/2/3 expression (1.7-, 3.9- and 5.9-fold) while ascending SMCs overexpressed TGFB1 and TGFB2 ligands (1.8- and 3.5-fold). Despite discordant TGF-ß activation, SMC contractile gene expression was similar between lineages in aortic and iPSC-SMCs, suggesting alternative downstream effects in LDS aneurysm. Conclusion: iPSC-derived SMCs effectively model lineage-specific aortic root aneurysm pathology, validating this model as a tool for mechanistic testing and therapy discovery.


2015 ◽  
Vol 465 (2) ◽  
pp. 185-194 ◽  
Author(s):  
Biraja C. Dash ◽  
Zhengxin Jiang ◽  
Carol Suh ◽  
Yibing Qyang

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.


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