Strategies for immune regulation in iPS cell-based cardiac regenerative medicine
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(2020) 40:36
Inflammation and Regeneration
REVIEW
Open Access
Strategies for immune regulation in iPS cell-based cardiac regenerative medicine Kozue Murata1,2, Masaya Ikegawa3, Kenji Minatoya2,4 and Hidetoshi Masumoto1,4*
Abstract Cardiac regenerative therapy is expected to be a promising therapeutic option for the treatment of severe cardiovascular diseases. Artificial tissues or organoids made from cardiovascular cell lineages differentiated from human induced pluripotent stem cells (iPSCs) are expected to regenerate the damaged heart. Even though immune rejection rarely occurs when iPSC-derived graft and the recipient have the same HLA type, in some cases, such as tissue transplantation onto hearts, the HLA matching would not be sufficient to fully control immune rejection. The present review introduces recent immunomodulatory strategies in iPSC-based transplantation therapies other than MHC matching including the induction of immune tolerance through iPSC-derived antigenpresenting cells, simultaneous transplantation of syngeneic mesenchymal stem cells, and using the universal donor cells such as gene editing-based HLA modulation in iPSCs to regulate T cell compatibility. In addition, we present future perspectives for proper adjustment of immunosuppression therapy after iPSC-derived tissue/organoid-based cardiac regenerative therapies by identifying biomarkers monitoring immune rejection. Keywords: Induced pluripotent stem cells, Transplantation, Immune regulation, Cardiac regeneration
Introduction Cardiovascular diseases are leading causes of death and medical expenditure worldwide even recent progresses in medical treatments [1]. Therapeutic modalities in severe heart diseases should be further investigated considering that chances in heart transplantation are quite limited due to donor shortage [2], and ventricular assist devices for circulatory support are not anticipated for long-term use due to complications such as thromboembolism, hemorrhage, and infection so far [3, 4]. Regenerative medicine is an emerging therapeutic option to provide new approaches in current cardiovascular medicine [5–8]. One of the key concepts in cardiac regenerative medicine is the supplementation of exogenous stem cells * Correspondence: [email protected] 1 Clinical Translational Research Program, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan 4 Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan Full list of author information is available at the end of the article
and the derivatives in cardiovascular cell lineages to restore damaged heart tissue structure and function [7, 9–13]. Pluripotent stem cells are expected to be promising cell sources in regenerative medicine for various intractable diseases by virtue of the theoretically infinite proliferative capacity and ability to differentiate into various types of somatic cells [14]. Especially, human induced pluripotent stem cells (iPSCs) are expecte
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