Human umbilical cord blood cells express neural antigens after transplantation into the developing rat brain.
Recently, our laboratory began to characterize the mononuclear cells from human umbilical cord blood (HUCB) both in vitro and in vivo. These cryopreserved human cells are available in unlimited quantities and it is believed that they may represent a source of cells with possible therapeutic and practical value. Our previous molecular and immunocytochemical studies on cultured HUCB cells revealed their ability to respond to nerve growth factor (NGF) by increased expression of neural markers typical for nervous system-derived stem cells. In addition, the DNA microarray detected downregulation of several genes associated with development of blood cell lines. To further explore the survival and phenotypic properties of HUCB cells we transplanted them into the developing rat brain, which is known to provide a conducive environment for development of neural phenotypes. Prior to transplantation, HUCB cells were either cultured with DMEM and fetal bovine serum or were exposed to retinoic acid (RA) and nerve growth factor (NGF). Neonatal pups (1 day old) received unilateral injection of cell suspension into the anterior part of subventricular zone. One month after transplantation animals were perfused, their brains cryosectioned, and immunocytochemistry was performed for identification of neural phenotypes. Our results clearly demonstrated that approximately 20% of transplanted HUCB survived (without immunosuppression) within the neonatal brain. Additionally, double-labeling with cell-type-specific markers revealed that some HUCB-derived cells (recognized by anti-human nuclei labeling) were immunopositive for glial fibrillary acidic protein (GFAP) and few donor cells expressed the neuronal marker TuJ1 (class III beta-tubulin). These findings suggest that at least some of the transplanted HUCB cells differentiated into cells with distinct glial or neuronal phenotypes after being exposed to instructive signals from the developing brain.
Zigova
Tanja
T
Center for Aging and Brain Repair, Department of Neurosurgery, University of South Florida College of Medicine, Tampa 33612, USA. tzigova@hsc.usf.edu
Song
Shijie
S
Willing
Alison E
AE
Hudson
Jennifer E
JE
Newman
Mary B
MB
Saporta
Samuel
S
Sanchez-Ramos
Juan
J
Sanberg
Paul R
PR
D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D019070:Cell Lineage; D002470:Cell Survival; D002478:Cells, Cultured; D036101:Cord Blood Stem Cell Transplantation; D005312:Fetal Blood / Q000166:cytology*; D016332:Fetal Tissue Transplantation; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D039902:Multipotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology / Q000637:transplantation*; D020932:Nerve Growth Factor / Q000494:pharmacology; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000737:chemistry / Q000378:metabolism*; D010641:Phenotype; D016548:Prosencephalon / Q000166:cytology / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D014404:Tubulin / Q000378:metabolism
D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D014404:Tubulin; D020932:Nerve Growth Factor