A cloaked human stem-cell-derived neural graft capable of functional integration and immune evasion in rodent models DOI Creative Commons
Chiara Pavan,

Kathryn C. Davidson,

Natalie L. Payne

и другие.

Cell stem cell, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

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 hPSC line (termed H1-FS-8IM), engineered overexpress 8 immunomodulatory transgenes, enable transplant immune evasion. In co-cultures, H1-FS-8IM PSC-derived midbrain evaded rejection by T lymphocytes, natural killer cells, macrophages, and dendritic cells. humanized mice, allogeneic neural grafts while control hPSC-derived evoked activation of human elevated inflammatory cytokines in blood cerebrospinal fluid, caused spleen lymph node enlargement. retained functionality, reversing motor deficits Parkinsonian rats. Additional incorporation suicide gene into the enabled proliferative elimination within grafts. Findings demonstrate feasibility population-wide applicable, safe, off-the-shelf product, suitable treating diseases which cell-based viable option.

Язык: Английский

A cloaked human stem-cell-derived neural graft capable of functional integration and immune evasion in rodent models DOI Creative Commons
Chiara Pavan,

Kathryn C. Davidson,

Natalie L. Payne

и другие.

Cell stem cell, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

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 hPSC line (termed H1-FS-8IM), engineered overexpress 8 immunomodulatory transgenes, enable transplant immune evasion. In co-cultures, H1-FS-8IM PSC-derived midbrain evaded rejection by T lymphocytes, natural killer cells, macrophages, and dendritic cells. humanized mice, allogeneic neural grafts while control hPSC-derived evoked activation of human elevated inflammatory cytokines in blood cerebrospinal fluid, caused spleen lymph node enlargement. retained functionality, reversing motor deficits Parkinsonian rats. Additional incorporation suicide gene into the enabled proliferative elimination within grafts. Findings demonstrate feasibility population-wide applicable, safe, off-the-shelf product, suitable treating diseases which cell-based viable option.

Язык: Английский

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