title: Human induced pluripotent stem cell-derived neural crest stem cells integrate into the injured spinal cord in the fetal lamb model of myelomeningocele.
abstract: OBJECTIVE
  Neurological function in patients with myelomeningocele (MMC) is limited even after prenatal repair. Neural crest stem cells (NCSCs) can improve neurological function in models of spinal cord injury. We aimed to evaluate the survival, integration, and differentiation of human NCSCs derived from induced pluripotent stem cells (iPSC-NCSCs) in the fetal lamb model of MMC.
  
  
  METHODS
  Human iPSCs derived from skin fibroblasts were differentiated into NCSCs in vitro, mixed with hydrogel, and seeded on nanofibrous scaffolds for surgical transplantation. Fetal lambs (n=2) underwent surgical MMC creation and repair with iPSC-NCSC seeded scaffolds. Gross necropsy and immunohistochemistry were performed at term.
  
  
  RESULTS
  IPSC-NCSCs expressed NCSC markers, maintained > 95% viability, and demonstrated neuronal differentiation in vitro. Immunohistochemical analysis of repaired spinal cords thirty days after transplantation demonstrated the co-localization of human nuclear mitotic apparatus protein (NuMA) and Neurofilament M subunit (NFM) in the area of spinal cord injury. No gross tumors were identified.
  
  
  CONCLUSIONS
  Human iPSC-NCSCs survived, integrated, and differentiated into neuronal lineage in the fetal lamb model of MMC. This is the first description of human stem cell engraftment in a model of fetal MMC and supports the concept of using NCSCs to address spinal cord damage in MMC.
authors: Division of Pediatric Surgery and Fetal Treatment Center, Department of Surgery, University of California, San Francisco, CA, USA.
authors: Payam
authors: P
authors: Saadai
authors: Aijun
authors: A
authors: Wang
authors: Yvette S
authors: YS
authors: Nout
authors: Timothy L
authors: TL
authors: Downing
authors: Katrine
authors: K
authors: Lofberg
authors: Michael S
authors: MS
authors: Beattie
authors: Jacqueline C
authors: JC
authors: Bresnahan
authors: Song
authors: S
authors: Li
authors: Diana L
authors: DL
authors: Farmer
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival; D004195:Disease Models, Animal; D046128:Fetal Therapies / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology / Q000637:transplantation*; D008591:Meningomyelocele / Q000601:surgery*; D009432:Neural Crest / Q000166:cytology*; D012756:Sheep; D054457:Tissue Scaffolds; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers