Do hematopoietic cells exposed to a neurogenic environment mimic properties of endogenous neural precursors?
Hematopoietic progenitors are cells, which under challenging experimental conditions can develop unusual phenotypic properties, rather distant from their original mesodermal origin. As previously reported, cells derived from human umbilical cord blood (HUCB) or human bone marrow (BM) under certain in vivo or in vitro conditions can manifest neural features that resemble features of neural-derived cells, immunocytochemically and in some instances also morphologically. The present study explored how hematopoietic-derived cells would respond to neurogenic signals from the subventricular zone (SVZ) of adult and aged (6 and 16 months old) rats. The mononuclear fraction of HUCB cells was transplanted into the SVZ of immunosuppressed (single cyclosporin or three-drug treatment) animals. The triple-suppression paradigm allowed us to protect transplanted human cells within the brain and to explore further their phenotypic and migratory properties. One week after implantation, many surviving HUCB cells were located within the SVZ and the vertical limb of the rostral migratory stream (RMS). The migration of HUCB cells was restricted exclusively to the pathway leading to the olfactory bulb. In younger animals, grafted cells navigated almost halfway through the vertical limb, whereas, in the older animals, the migration was less pronounced. The overall cell survival was greater in younger animals than in older ones. Immunocytochemistry for surface CD antigen expression showed that many HUCB cells, either cultured or within the brain parenchyma, retained their hematopoietic identity. A few cells, identified by using human-specific antibodies (anti-human nuclei, or mitochondria) expressed nestin and doublecortin, markers of endogenous neural progenitors. Therefore, it is believed that the environment of the neurogenic SVZ, even in aged animals, was able to support survival, "neuralization," and migratory features of HUCB-derived cells.
Walczak
P
P
Center of Excellence for Aging and Brain Repair, Department of Neurosurgery, University of South Florida College of Medicine, Tampa, Florida 33612, USA. pwalczak@hsc.usf.edu
Chen
N
N
Hudson
J E
JE
Willing
A E
AE
Garbuzova-Davis
S N
SN
Song
S
S
Sanberg
P R
PR
Sanchez-Ramos
J
J
Bickford
P C
PC
Zigova
T
T
D000367:Age Factors; D000818:Animals; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D051926:Basigin; D001798:Blood Proteins; D001854:Bone Marrow Cells / Q000502:physiology; D002452:Cell Count; D002454:Cell Differentiation; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002552:Cerebral Ventricles / Q000378:metabolism; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods; D000089662:Doublecortin Protein; D004777:Environment; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007211:Indoles / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology / Q000637:transplantation*; D009474:Neurons / Q000737:chemistry / Q000378:metabolism*; D010641:Phenotype; D051381:Rats; D011916:Rats, Inbred F344; D014404:Tubulin / Q000378:metabolism
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; C497886:BSG protein, human; D001798:Blood Proteins; C102624:Bsg protein, Gallus gallus; C497887:Bsg protein, mouse; C079432:Bsg protein, rat; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D005904:Glial Fibrillary Acidic Protein; D007166:Immunosuppressive Agents; D007211:Indoles; D008164:Luminescent Proteins; D008562:Membrane Glycoproteins; D014404:Tubulin; C462941:beta3 tubulin, mouse; D051926:Basigin; D049452:Green Fluorescent Proteins; C007293:DAPI; D017493:Leukocyte Common Antigens