Open AccessDevelopment of Histocompatible Primate‐Induced Pluripotent Stem Cells for Neural Transplantation
Author(s) -
Deleidi Michela,
Hargus Gunnar,
Hallett Penelope,
Osborn Teresia,
Isacson Ole
Publication year - 2011
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.662
Subject(s) - induced pluripotent stem cell , biology , transplantation , major histocompatibility complex , neuroscience , dopaminergic , microbiology and biotechnology , immunology , immune system , embryonic stem cell , genetics , dopamine , medicine , gene
Immune rejection and risk of tumor formation are perhaps the greatest hurdles in the field of stem cell transplantation. Here, we report the generation of several lines of induced pluripotent stem cells (iPSCs) from cynomolgus macaque (CM) skin fibroblasts carrying specific major histocompatibility complex (MHC) haplotypes. To develop a collection of MHC‐matched iPSCs, we genotyped the MHC locus of 25 CMs by microsatellite polymerase chain reaction analysis. Using retroviral infection of dermal skin fibroblasts, we generated several CM‐iPSC lines carrying different haplotypes. We characterized the immunological properties of CM‐iPSCs and demonstrated that CM‐iPSCs can be induced to differentiate in vitro along specific neuronal populations, such as midbrain dopaminergic (DA) neurons. Midbrain‐like DA neurons generated from CM‐iPSCs integrated into the striatum of a rodent model of Parkinson's disease and promoted behavioral recovery. Importantly, neither tumor formation nor inflammatory reactions were observed in the transplanted animals up to 6 months after transplantation. We believe that the generation and characterization of such histocompatible iPSCs will allow the preclinical validation of safety and efficacy of iPSCs for neurodegenerative diseases and several other human conditions in the field of regenerative medicine. S TEM C ELLS 2011;29:1052–1063