title: Application of human persistent fetal vasculature neural progenitors for transplantation in the inner retina.
abstract: Persistent fetal vasculature (PFV) is a potentially serious developmental anomaly in human eyes, which results from a failure of the primary vitreous and the hyaloid vascular systems to regress during development. Recent findings from our laboratory indicate that fibrovascular membranes  harvested from subjects with PFV contain neural progenitor cells (herein called NPPFV cells). Our studies on successful isolation, culture, and characterization of NPPFV cells have shown that they highly express neuronal progenitor markers (nestin, Pax6, and Ki67) as well as retinal neuronal  markers (β-III-tubulin and Brn3a). In the presence of retinoic acid and neurotrophins, these cells acquire a neural morphological appearance in vitro, including a round soma and extensive neurites, and express mature neuronal markers (β-III-tubulin and NF200). Further experiments,  including real-time qRT-PCR to quantify characteristic gene expression profiles of these cells and Ca(2+) imaging to evaluate the response to stimulation with different neurotransmitters, indicate that NPPFV cells may resemble a more advanced stage of retinal development and show  more differentiation toward inner retinal neurons rather than photoreceptors. To explore the potential of inner retinal transplantation, NPPFV cells were transplanted intravitreally into the eyes of adult C57BL/6 mice. Engrafted NPPFV cells survived well in the intraocular environment in presence  of rapamycin and some cells migrated into the inner nuclear layer of the retina 1 week posttransplantation. Three weeks after transplantation, NPPFV cells were observed to migrate and integrate in the inner retina. In response to daily intraperitoneal injections of retinoic acid, a portion  of transplanted NPPFV cells exhibited retinal ganglion cell-like morphology and expressed mature neuronal markers (β-III-tubulin and synaptophysin). These findings indicate that fibrovascular membranes from human PFV harbor a population of neuronal progenitors that may be potential candidates  for cell-based therapy for degenerative diseases of the inner retina.
authors: Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China.
authors: Guochun
authors: G
authors: Chen
authors: Jie
authors: J
authors: Ma
authors: Marie A
authors: MA
authors: Shatos
authors: Huihui
authors: H
authors: Chen
authors: Desirée
authors: D
authors: Cyr
authors: Kameran
authors: K
authors: Lashkari
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism; D055351:Retinal Neurons / Q000166:cytology / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology; D016708:Synaptophysin / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism; D014822:Vitreous Body / Q000166:cytology*
chemical_list: D016708:Synaptophysin; C498585:TUBB3 protein, human; D014404:Tubulin; D014212:Tretinoin; D002118:Calcium; D020123:Sirolimus