A cloaked human stem-cell-derived neural graft capable of functional integration and immune evasion in rodent models

Pavan, C; Davidson, KC; Payne, N; Frausin, S; Hunt, CPJ; Moriarty, N; Berrocal Rubio, M&#193;; Elahi, Z; Quattrocchi, AT; Abu-Bonsrah, KD; Wang, L; Clow, W; Yang, H; Pellegrini, M; Wells, CA; Thompson, LH; Nagy, A; Parish, CL

Author(s): Pavan, C; Davidson, KC; Payne, N; Frausin, S; Hunt, CPJ; Moriarty, N; Berrocal Rubio, MÁ; Elahi, Z; Quattrocchi, AT; Abu-Bonsrah, KD; Wang, L; Clow, W; Yang, H; Pellegrini, M; Wells, CA; Thompson, LH; Nagy, A; Parish, CL;
Details: Publication Year 2025-05-01,Volume 32,Issue #5,Page 710-726.e8
Journal Title: Cell Stem Cell
Abstract: Human pluripotent stem cell (hPSC)-derived therapies are a realistic possibility for numerous disorders, including Parkinson's disease. While generating replacement neurons is achievable, immunosuppressive drug challenges, to prevent rejection, remain. Here we adopted a hPSC line (termed H1-FS-8IM), engineered to overexpress 8 immunomodulatory transgenes, to enable transplant immune evasion. In co-cultures, H1-FS-8IM PSC-derived midbrain neurons evaded rejection by T lymphocytes, natural killer cells, macrophages, and dendritic cells. In humanized mice, allogeneic H1-FS-8IM neural grafts evaded rejection, while control hPSC-derived neural grafts evoked activation of human immune cells, elevated inflammatory cytokines in blood and cerebrospinal fluid, and caused spleen and lymph node enlargement. H1-FS-8IM neural grafts retained functionality, reversing motor deficits in Parkinsonian rats. Additional incorporation of a suicide gene into the H1-FS-8IM hPSC line enabled proliferative cell elimination within grafts. Findings demonstrate feasibility of generating a population-wide applicable, safe, off-the-shelf cell product, suitable for treating diseases for which cell-based therapies are a viable option.
Publisher: Cell Press
Keywords: Animals; Humans; Rats; Mice; Disease Models, Animal; *Immune Evasion; *Pluripotent Stem Cells/cytology; *Neurons/cytology/transplantation; *Neural Stem Cells/transplantation; Coculture Techniques; *Stem Cell Transplantation; Cell Line; Parkinson’s disease; allografting; dopamine; graft integration; graft rejection; human pluripotent stem cells; immune evasion; suicide gene; transplantation
Research Division(s): Infection and Global Health
PubMed ID: 40209717
Publisher's Version: https://doi.org/10.1016/j.stem.2025.03.008
Open Access at Publisher's Site: https://doi.org/10.1016/j.stem.2025.03.008
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-05-06 09:17:37

Last Modified: 2025-05-06 09:17:46