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

Giulia Nato, Alessandro Corti, Elena Parmigiani, Elena Jachetti, Daniele Lecis, Mario Paolo Colombo, Domenico Delia, Annalisa Buffo, Lorenzo Magrassi

Research output: Contribution to journalArticlepeer-review

Abstract

We xeno-transplanted human neural precursor cells derived from induced pluripotent stem cells into the cerebellum and brainstem of mice and rats during prenatal development or the first postnatal week. The transplants survived and started to differentiate up to 1 month after birth when they were rejected by both species. Extended survival and differentiation of the same cells were obtained only when they were transplanted in NOD-SCID mice. Transplants of human neural precursor cells mixed with the same cells after partial in vitro differentiation or with a cellular extract obtained from adult rat cerebellum increased survival of the xeno-graft beyond one month. These findings are consistent with the hypothesis that the slower pace of differentiation of human neural precursors compared to that of rodents restricts induction of immune-tolerance to human antigens expressed before completion of maturation of the immune system. With further maturation the transplanted neural precursors expressed more mature antigens before the graft were rejected. Supplementation of the immature cells suspensions with more mature antigens may help to induce immune-tolerance for those antigens expressed only later by the engrafted cells.

Original languageEnglish
Article number651
JournalScientific Reports
Volume11
Issue number1
DOIs
Publication statusPublished - Dec 2021

ASJC Scopus subject areas

  • General

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