Direct Comparison of Autologous and Allogeneic Transplantation of iPSC-Derived Neural Cells in the Brain of a Nonhuman Primate

Asuka Morizane,Daisuke Doi,Tetsuhiro Kikuchi,Keisuke Okita,Akitsu Hotta,Toshiyuki Kawasaki,Takuya Hayashi,Hirotaka Onoe,Takashi Shiina,Shinya Yamanaka,Jun Takahashi

doi:10.1016/j.stemcr.2013.08.007

Asuka Morizane, Daisuke Doi + Show 9 more

Open Access

https://doi.org/10.1016/j.stemcr.2013.08.007

Copy DOI

Abstract

SummaryInduced pluripotent stem cells (iPSCs) provide the potential for autologous transplantation using cells derived from a patient’s own cells. However, the immunogenicity of iPSCs or their derivatives has been a matter of controversy, and up to now there has been no direct comparison of autologous and allogeneic transplantation in the brains of humans or nonhuman primates. Here, using nonhuman primates, we found that the autologous transplantation of iPSC-derived neurons elicited only a minimal immune response in the brain. In contrast, the allografts caused an acquired immune response with the activation of microglia (IBA-1+/MHC class II+) and the infiltration of leukocytes (CD45+/CD3+). Consequently, a higher number of dopaminergic neurons survived in the autografts. Our results suggest that the autologous transplantation of iPSC-derived neural cells is advantageous for minimizing the immune response in the brain compared with allogeneic grafts.

Highlights

In recent studies, murine induced pluripotent stem cell-derived teratomas in the subcutaneous space induced an immune response in syngeneic mice (Zhao et al, 2011)
The immunogenicity of Induced pluripotent stem cells (iPSCs) or their derivatives has been a matter of controversy, and up to now there has been no direct comparison of autologous and allogeneic transplantation in the brains of humans or nonhuman primates
Using nonhuman primates, we found that the autologous transplantation of iPSC-derived neurons elicited only a minimal immune response in the brain

Summary

Introduction

Murine induced pluripotent stem cell (iPSC)-derived teratomas in the subcutaneous space induced an immune response in syngeneic mice (Zhao et al, 2011). Syngeneic transplantation of skin and bone marrow tissues (Araki et al, 2013) or endothelial, hepatic, and neuronal cells (Guha et al, 2013) derived from iPSCs showed a limited or no immune response, respectively. These rodent studies investigated the immunogenicity of teratomas, chimeric mouse-derived tissues, or ectopic grafts, but did not convincingly simulate the clinical situation. In order to assess the immunogenicity of iPSC-derived neural cells in a primate brain, we generated iPSCs from four cynomolgus monkeys and directly compared the autologous and allogeneic transplantation of iPSC-derived neural cells

Results

Discussion

Conclusion