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Human-Induced Pluripotent Stem Cell-Derived Neural Stem Cell Therapy Limits Tissue Damage and Promotes Tissue Regeneration and Functional Recovery in a Pediatric Piglet Traumatic-Brain-Injury Model.
Schantz, Sarah L; Sneed, Sydney E; Fagan, Madison M; Golan, Morgane E; Cheek, Savannah R; Kinder, Holly A; Duberstein, Kylee J; Kaiser, Erin E; West, Franklin D.
Afiliación
  • Schantz SL; Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, USA.
  • Sneed SE; Biomedical and Health Sciences Institute, University of Georgia, Athens, GA 30602, USA.
  • Fagan MM; Animal and Dairy Science Department, College of Agricultural and Environmental Sciences, University of Georgia, Athens, GA 30602, USA.
  • Golan ME; Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, USA.
  • Cheek SR; Animal and Dairy Science Department, College of Agricultural and Environmental Sciences, University of Georgia, Athens, GA 30602, USA.
  • Kinder HA; Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, USA.
  • Duberstein KJ; Biomedical and Health Sciences Institute, University of Georgia, Athens, GA 30602, USA.
  • Kaiser EE; Animal and Dairy Science Department, College of Agricultural and Environmental Sciences, University of Georgia, Athens, GA 30602, USA.
  • West FD; Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, USA.
Biomedicines ; 12(8)2024 Jul 25.
Article en En | MEDLINE | ID: mdl-39200128
ABSTRACT
Traumatic brain injury (TBI) is a leading cause of death and disability in pediatric patients and often results in delayed neural development and altered connectivity, leading to lifelong learning, memory, behavior, and motor function deficits. Induced pluripotent stem cell-derived neural stem cells (iNSCs) may serve as a novel multimodal therapeutic as iNSCs possess neuroprotective, regenerative, and cell-replacement capabilities post-TBI. In this study, we evaluated the effects of iNSC treatment on cellular, tissue, and functional recovery in a translational controlled cortical impact TBI piglet model. Five days post-craniectomy (n = 6) or TBI (n = 18), iNSCs (n = 7) or PBS (n = 11) were injected into perilesional brain tissue. Modified Rankin Scale (mRS) neurological evaluation, magnetic resonance imaging, and immunohistochemistry were performed over the 12-week study period. At 12-weeks post-transplantation, iNSCs showed long-term engraftment and differentiation into neurons, astrocytes, and oligodendrocytes. iNSC treatment enhanced endogenous neuroprotective and regenerative activities indicated by decreasing intracerebral immune responses, preserving endogenous neurons, and increasing neuroblast formation. These cellular changes corresponded with decreased hemispheric atrophy, midline shift, and lesion volume as well as the preservation of cerebral blood flow. iNSC treatment increased piglet survival and decreased mRS scores. The results of this study in a predictive pediatric large-animal pig model demonstrate that iNSC treatment is a robust multimodal therapeutic that has significant promise in potentially treating human pediatric TBI patients.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Biomedicines Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Biomedicines Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza