TIPE2-modified human amnion-derived mesenchymal stem cells promote the efficacy of allogeneic heart transplantation through inducing immune tolerance

Feng Wang; Guanping Yao; Sisi Pan; Xin Mao; Xu Zhao; Chuntian Li; Zheng Hong; Guiyou Liang; Limei Yu; Xuanyi Hu; Wanfu Peng

doi:10.21037/jtd-21-1034

TIPE2-modified human amnion-derived mesenchymal stem cells promote the efficacy of allogeneic heart transplantation through inducing immune tolerance

J Thorac Dis. 2021 Aug;13(8):5064-5076. doi: 10.21037/jtd-21-1034.

Authors

Feng Wang^{1

2

3

4}, Guanping Yao⁵, Sisi Pan¹, Xin Mao⁶, Xu Zhao⁶, Chuntian Li⁶, Zheng Hong⁶, Guiyou Liang^{1

4}, Limei Yu⁵, Xuanyi Hu⁴, Wanfu Peng⁴

Affiliations

¹ Department of Clinical Medical College, Guizhou Medical University, Guiyang, China.
² Department of Cardiac Surgery, The Affiliated Hospital of Zunyi Medical University, Zunyi, China.
³ Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, China.
⁴ Department of Cardiac Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
⁵ Department of Guizhou Regenerative Medicine Laboratory, The Affiliated Hospital of Zunyi Medical University, Zunyi, China.
⁶ Department of Clinical Medical College, Zunyi Medical University, Zunyi, China.

Abstract

Background: Immune rejection of heart transplantation has been regarded as the biggest challenge encountered by a patient suffering from end-stage heart disease. The transplantation of human amnion-derived mesenchymal stem cells (hAD-MSCs) has exhibited promising application prospects in organ transplantation. However, its persistent unsatisfactory tolerance has limited the widespread application of this technology. We aim to investigate the role of tumor necrosis factor-α-induced protein-8 like-2 (TIPE2)-mediated hAD-MSCs in immune tolerance in heart transplantation and its molecular regulatory mechanisms.

Methods: This project detected the effect of TIPE2 on immune tolerance by constructing an allogeneic heart transplantation mouse model through which TIPE2-overexpressed hAD-MSCs were injected into recipients. The fluorescence distribution of TIPE2-hAD-MSCs in mice was observed by a small animal in vivo imaging system. Pathological changes of the transplanted heart were detected by hematoxylin and eosin (HE) staining. Flow cytometry was performed to detect the content of cardiac lymphocytes. The expression of immune-induced related factors was measured by quantitative real-time PCR (qRT-PCR) and western blot assays.

Results: TIPE2-hAD-MSCs protected myocardial tissue structures, reduced the spleen and thymus indexes in recipient mice, minimized the content of cardiac lymphocytes, reduced expressions of ERK, p38, and IFN-γ, and elevated expressions of both IL-10 and TGF-β, markedly improving the survival time and survival rates of recipient mice.

Conclusions: TIPE2-hAD-MSCs induce immune tolerance and improve the survival rates of allogeneic heart transplantation in mice. This study is expected to offer an ideal source and target of cells for organ transplantation.

Keywords: Tumor necrosis factor-α-induced protein-8 like-2 (TIPE2); heart transplantation; human amnion-derived mesenchymal stem cells (hAD-MSCs); immune tolerance.