Low immunogenicity of mouse induced pluripotent stem cell-derived neural stem/progenitor cells

Abstract

Resolving the immunogenicity of cells derived from induced pluripotent stem cells (iPSCs) remains an important challenge for cell transplant strategies that use banked allogeneic cells. Thus, we evaluated the immunogenicity of mouse fetal neural stem/progenitor cells (fetus-NSPCs) and iPSC-derived neural stem/progenitor cells (iPSC-NSPCs) both in vitro and in vivo. Flow cytometry revealed the low expression of immunological surface antigens, and these cells survived in all mice when transplanted syngeneically into subcutaneous tissue and the spinal cord. In contrast, an allogeneic transplantation into subcutaneous tissue was rejected in all mice, and allogeneic cells transplanted into intact and injured spinal cords survived for 3 months in approximately 20% of mice. In addition, cell survival was increased after co-treatment with an immunosuppressive agent. Thus, the immunogenicity and post-transplantation immunological dynamics of iPSC-NSPCs resemble those of fetus-NSPCs.

Immune-tolerance to human iPS-derived neural progenitors xenografted into the immature cerebellum is overridden by species-specific differences in differentiation timing

“…Our results also indicate that, at least in vitro, hiPSdNP but not their more differentiated derivatives, were able to partially suppress the proliferation of murine CD4 and CD8 T cells. An immunosuppressive activity mediated by TGFß has also been described for NP derived from primate IPSC cells 44 . The direct immunosuppressive activity of hiPSdNP may have complemented the immuno-tolerance induced by xeno-transplantation of the cells before complete maturation of the host immune system in the initial xeno-graft survival.…”

“…In immunocompromised mice the maturation process together with extensive migration of the cells homing in portions of the cerebellum and brainstem away from the original sites of transplant, progressed in the following months, while all grafted cells disappeared in immune-competent animals around the end of the first month. Immune rejection by activation of cellular immunity after allogenic transplantation of iPSC-derived neurons is well documented in rodents and primates 44 .…”

Grafted human induced pluripotent stem cells improve the outcome of spinal cord injury: modulation of the lesion microenvironment

“…The iPSCs can be produced from somatic cells such as dermal fibroblasts, keratinocytes or blood cells by transient overexpression of defined transcription factors, such as Oct3/4, Sox2, Klf4, and c-Myc (known as OSKM factors) 11 , 12 . Human iPSCs display similar morphology, proliferation capacity, surface antigens expression, gene expression characteristics as embryonic stem cells 11 – 14 . Moreover, transplantation of iPSC derivatives reportedly does not generate significant host immune response 15 , 16 .…”

Cortical Transplantation of Brain‐Mimetic Glycosaminoglycan Scaffolds and Neural Progenitor Cells Promotes Vascular Regeneration and Functional Recovery after Ischemic Stroke in Mice

“…For translational cellular therapy purposes, the two main sources of NPCs include embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Unlike ESCs, iPSC derived neural progenitor cells can be generated autologously from the host somatic cells, bypassing potential ethical concerns surrounding the use of cells derived from embryos, and potentially reducing immunogenicity compared to allogeneic cell sources . Our lab has previously used iPSC‐derived NPCs for the treatment of ischemic stroke and traumatic brain injury in rodent models .…”