Development of composite functional tissue sheets using hiPSC-CMs and hADSCs to improve the cardiac function after myocardial infarction

Jingbo Zhang; Junjun Li; Xiang Qu; Yuting Liu; Lifu Sun; Akima Harada; Ying Hua; Nagako Sougawa; Akiko Tabata; Li Liu; Shigeru Miyagawa

doi:10.1016/j.bioactmat.2024.03.028

Development of composite functional tissue sheets using hiPSC-CMs and hADSCs to improve the cardiac function after myocardial infarction

Bioact Mater. 2024 Apr 25:37:533-548. doi: 10.1016/j.bioactmat.2024.03.028. eCollection 2024 Jul.

Authors

Jingbo Zhang¹, Junjun Li^{1

2}, Xiang Qu³, Yuting Liu¹, Lifu Sun¹, Akima Harada¹, Ying Hua¹, Nagako Sougawa^{1

4}, Akiko Tabata¹, Li Liu^{1

2}, Shigeru Miyagawa¹

Affiliations

¹ Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Osaka, 565-0871, Japan.
² Department of Applied Physics Osaka University, Osaka University, 2-2 Yamada-oka, Osaka, 565-0871, Japan.
³ Frontier of Regenerative Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan.
⁴ Department of Physiology, Osaka Dental University, 8-1 Kuzuha Hanazono-cho, Hirakata, 573-1121, Japan.

Abstract

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been widely used in therapy of ischemic heart disease. However, there are still remaining issues that limit the therapeutic efficacy, such as immune rejection and low retention of hiPSC-CMs. Human adipose mesenchymal stromal cells (hADSCs) have been reported to be able to regulate the immune response, promote angiogenesis and promote the maturation of hiPSC-CMs. In this study, we co-cultured these two types of cells on fiber scaffold made of biodegradable poly (D,L-lactic-co-glycolic acid) (PLGA) polymer for several days to develop a composited 3D cardiac tissue sheet. As expected, the cells formed 231.00 ± 15.14 μm thickness tissue, with improved organization, alignment, ECM condition, contractile ability, and paracrine function compared to culture hiPSC-CMs only on PLGA fiber. Furthermore, the composited 3D cardiac tissue sheet significantly promoted the engraftment and survival after transplantation. The composited 3D cardiac tissue sheet also increased cardiac function, attenuated ventricular remodeling, decreased fibrosis, and enhanced angiogenesis in rat myocardial infarction model, indicating that this strategy wound be a promising therapeutic option in the clinical scenario.

Keywords: Human adipose-derived mesenchymal stem cell; Human induced pluripotent stem cell-derived cardiomyocyte; Myocardial infarction; Regenerative medicine; Tissue engineering.