Human induced pluripotent stem cells improve stroke outcome and reduce secondary degeneration in the recipient brain.
Human induced pluripotent stem cells (hiPSCs) are a most appealing source for cell replacement therapy in acute brain lesions. We evaluated the potential of hiPSC therapy in stroke by transplanting hiPSC-derived neural progenitor cells (NPCs) into the postischemic striatum. Grafts received  host tyrosine hydroxylase-positive afferents and contained developing interneurons and homotopic GABAergic medium spiny neurons that, with time, sent axons to the host substantia nigra. Grafting reversed stroke-induced somatosensory and motor deficits. Grafting also protected the host substantia  nigra from the atrophy that follows disruption of reciprocal striatonigral connections. Graft innervation by tyrosine hydoxylase fibers, substantia nigra protection, and somatosensory functional recovery were early events, temporally dissociated from the slow maturation of GABAergic neurons  in the grafts and innervation of substantia nigra. This suggests that grafted hiPSC-NPCs initially exert trophic effects on host brain structures, which precede integration and potential pathway reconstruction. We believe that transplantation of NPCs derived from hiPSCs can provide useful  interventions to limit the functional consequences of stroke through both neuroprotective effects and reconstruction of impaired pathways.
I-Stem, INSERM UMR861, UEVE, Evry Cedex, France.
Jérôme
J
Polentes
Pavla
P
Jendelova
Michel
M
Cailleret
Holger
H
Braun
Nataliya
N
Romanyuk
Philippe
P
Tropel
Marion
M
Brenot
Valerie
V
Itier
Christine
C
Seminatore
Kathrin
K
Baldauf
Karolina
K
Turnovcova
Daniel
D
Jirak
Marius
M
Teletin
Julien
J
Côme
Johana
J
Tournois
Klaus
K
Reymann
Eva
E
Sykova
Stéphane
S
Viville
Brigitte
B
Onteniente
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D002460:Cell Line; D058732:Embryoid Bodies / Q000473:pathology; D059330:GABAergic Neurons / Q000166:cytology / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D058953:Neural Stem Cells / Q000166:cytology / Q000637:transplantation; D020521:Stroke / Q000628:therapy*; D013724:Teratoma / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D014157:Transcription Factors; D014446:Tyrosine 3-Monooxygenase