Analysis of neural potential of human umbilical cord blood-derived multipotent mesenchymal stem cells in response to a range of neurogenic stimuli.
We investigated the neurogenic potential of full-term human umbilical cord blood (hUCB)-derived multipotent mesenchymal stem cells (MSCs) in response to neural induction media or coculture with rat neural cells. Phenotypic and functional changes were assessed by immunocytochemistry, RT-PCR, and whole-cell patch-clamp recordings. Naive MSCs expressed both mesodermal and ectodermal markers prior to neural induction. Exposure to retinoic acid, basic fibroblast growth factor, or cyclic adenosine monophosphate (cAMP) did not stimulate neural morphology, whereas exposure to dibutyryl cAMP and 3-isobutyl-1-methylxanthine stimulated a neuron-like morphology but also appeared to be cytotoxic. All protocols stimulated increases in expression of the neural precursor marker nestin, but expression of mature neuronal or glial markers MAP2 and GFAP was not observed. Nestin expression increases were serum level dependent. Electrophysiological properties of MSCs were studied with whole-cell patch-clamp recordings. The MSCs possessed no ionic currents typical of neurons before or after neural induction protocols. Coculture of hUCB-derived MSCs and rat neural cells induced some MSCs to adopt an astrocyte-like morphology and express GFAP protein and mRNA. Our data suggest hUCB-derived MSCs do not transdifferentiate into mature functioning neurons in response to the above neurogenic protocols; however, coculture with rat neural cells led to a minority adopting an astrocyte-like phenotype.
Zwart
Isabel
I
Department of Cellular and Molecular neuroscience, Imperial College, London, United Kingdom.
Hill
Andrew J
AJ
Girdlestone
John
J
Manca
Maria F
MF
Navarrete
Roberto
R
Navarrete
Cristina
C
Jen
Ling-Sun
LS
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D017077:Culture Media, Conditioned; D000242:Cyclic AMP / Q000502:physiology; D017931:DNA Primers; D005312:Fetal Blood / Q000166:cytology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007231:Infant, Newborn; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000502:physiology; D018408:Patch-Clamp Techniques; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000187:drug effects / Q000196:embryology; D014212:Tretinoin / Q000494:pharmacology
D017077:Culture Media, Conditioned; D017931:DNA Primers; D009419:Nerve Tissue Proteins; D016222:Fibroblast Growth Factor 2; D014212:Tretinoin; D003994:Bucladesine; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine