Transplantation of human umbilical cord blood-derived adherent progenitors into the developing rodent brain.
The results of several recent studies suggest that human umbilical cord blood (HUCB)-derived cells have the potential to undergo neural differentiation both in vitro and in vivo. Transplantation into the embryonic ventricular zone provides a unique opportunity to study the migration and differentiation of nonneural somatic progenitor cells in response to instructive cues within the developing neuroepithelium. We isolated an adherently growing population of HUCB-derived cells expressing CD13, CD29, CD49e, CD71, CD73, CD166, Flk-1, and vimentin but lacking CD34 and CD45. On transplantation into the ventricles of embryonic day 16.5 rat embryos, these cells formed subventricular clusters that extended into a variety of host brain regions, including striatum, cortex, hippocampus, thalamus, hypothalamus, tectum, pons, and cerebellum. Donor cells identified with an antibody to human nuclei or human-specific DNA in situ hybridization maintained expression of their original marker antigens and showed no expression of the neural markers MAP2 and NeuN (neurons), GFAP (astrocytes), and CNP (oligodendrocytes). In contrast to grafted primary neural cells, they remained largely confined to subventricular clusters with little evidence for intraparenchymal integration. Thus, the neurogenic environment of the embryonic ventricular zone does not promote the elaboration of a neural phenotype in HUCB-derived cells.
Coenen
Martin
M
Institute of Reconstructive Neurobiology, University of Bonn Life & Brain Center and Hertie Foundation, Bonn, Germany.
Kögler
Gesine
G
Wernet
Peter
P
Brüstle
Oliver
O
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000145:classification / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D036101:Cord Blood Stem Cell Transplantation; D004622:Embryo, Mammalian; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D005455:Fluorescent Antibody Technique / Q000379:methods; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D039902:Multipotent Stem Cells / Q000502:physiology / Q000637:transplantation*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009474:Neurons / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014746:Vimentin / Q000378:metabolism
D015703:Antigens, CD; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D014746:Vimentin; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D010751:Phosphopyruvate Hydratase