A Novel Insight into Endothelial and Cardiac Cells Phenotype in Systemic Sclerosis Using Patient-Derived Induced Pluripotent Stem Cell

(Pages: 273-287)
Sedigheh Gholami, Ph.D., 1,2Zahra Mazidi, M.Sc., 1Sara Pahlavan, Ph.D., 1Fariba Moslem, M.Sc., 1Mahya Hosseini, M.Sc., 1Adeleh Taei, Ph.D., 1Mahdi Hesaraki, M.Sc., 1Maryam Barekat, M.D., 3Nasser Aghdami, M.D., Ph.D., 3,*Hossein Baharvand, Ph.D., 1,2,*
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
Department of Developmental Biology, University of Science and Culture, Tehran, Iran
Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
Department of Developmental Biology, University of Science and Culture, Tehran, Iran
Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
*Corresponding Addresses: P.O.Box: 16635-148 Department of Regenerative Medicine Cell Science Research Center Royan Institute for Stem Cell Biology and Technology ACECR Tehran Iran P.O.Box: 16635-148 Department of Stem Cells and Developmental Biology Cell Science Research Center Royan Institute for Stem Cell Biology and Technology ACECR Tehran Iran Emails:nasser.aghdami@royaninstitute.org,baharvand@royaninstitute.org
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Gholami Sedigheh, Mazidi Zahra, Pahlavan Sara, Moslem Fariba, Hosseini Mahya, Taei Adeleh, Hesaraki Mahdi, Barekat Maryam, Aghdami Nasser, Baharvand Hossein. A Novel Insight into Endothelial and Cardiac Cells Phenotype in Systemic Sclerosis Using Patient-Derived Induced Pluripotent Stem Cell. Cell J. 2021; 23(3): 273-287.

Abstract

Objective

Systemic sclerosis (SSc) is a connective tissue disease associated with vascular damage and multi organ fibrotic changes with unknown pathogenesis. Most SSc patients suffer from defective angiogenesis/vasculogenesis and cardiac conditions leading to high mortality rates. We aimed to investigate the cardiovascular phenotype of SSc by cardiogenic differentiation of SSc induced pluripotent stem cells (iPSC).

Materials and Methods

In this experimental study, we generated iPSC from two diffuse SSc patients, followed by successful differentiation into endothelial cells (ECs) and cardiomyocytes (CMs).

Results

SSc-derived EC (SSc-EC) expressed KDR, a nearly EC marker, similar to healthy control-EC (C1-EC). After sorting and culturing KDR+ cells, the resulting EC expressed CD31, a late endothelial marker, but vascular endothelial (VE)-cadherin expression markedly dropped resulting in a functional defect as reflected in tube formation failure of SSc-EC. Interestingly, upregulation of SNAI1 (snail family transcriptional repressor 1) was observed in SSc-EC which might underlie VE-cadherin downregulation. Furthermore, SSc-derived CM (SSc-CM) successfully expressed cardiac- specific markers including ion channels, resulting in normal physiological behavior and responsiveness to cardioactive drugs.

Conclusion

This study provides an insight into impaired angiogenesis observed in SSc patients by evaluating in vitro cardiovascular differentiation of SSc iPSC.