Long-term cultured human umbilical cord neural-like cells transplanted into the striatum of NOD SCID mice.
The use of stem cells and other cells as therapies is still in its infancy. One major setback is the limited survival of the grafts, possibly due to immune rejection. Studies were therefore performed with human umbilical cord blood cells (HUCB) to determine the ability of these cells to survive in vivo and the effect of the immune response on their survival by transplantation into the normal striatum of immunodeficient NOD SCID mice. Long-term culture of HUCB cells resulted in several different populations of cells, including one that possessed fine processes and cell bodies that resembled neurons. Their neuronal phenotype was confirmed by immunohistochemical staining for the early neuronal marker TuJ1 and the potentially neural marker Nestin. Five days after cell transplantation of this neuronal phenotype, immunohistochemical staining for human mitochondria confirmed the presence of living HUCB cells in the mouse striatum, with cells localized at the site of injection, expressing early neural and neuronal markers (Nestin and TuJ1) as well as exhibiting neuronal morphology. However, no evidence of surviving cells was apparent 1 month postgrafting. The absence of signs of T cell-mediated rejection, such as CD4 and CD8 lymphocytes and minimal changes in microglia and astrocytes, suggest that cell loss was not due to a T cell-mediated immune response. In conclusion HUCB cells can survive long-term in vitro and undergo neuron-like differentiation. In mice, these cells do not survive a month. This may relate to the differentiated state of the cells transplanted into the unlesioned striatum, rather than T cell-mediated immunological rejection.
Center of Excellence for Aging and Brain Repair, University of South Florida, College of Medicine, Tampa, FL, USA.
Piotr
P
Walczak
Ning
N
Chen
David
D
Eve
Jennifer
J
Hudson
Tanja
T
Zigova
Juan
J
Sanchez-Ramos
Paul R
PR
Sanberg
Cyndy D
CD
Sanberg
Alison E
AE
Willing
D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D036101:Cord Blood Stem Cell Transplantation; D003342:Corpus Striatum / Q000166:cytology / Q000601:surgery*; D005312:Fetal Blood / Q000166:cytology* / Q000502:physiology*; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D039902:Multipotent Stem Cells / Q000166:cytology / Q000502:physiology* / Q000637:transplantation; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D013997:Time Factors; D014183:Transplantation, Heterologous; D014404:Tubulin / Q000378:metabolism
D039481:CD11b Antigen; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D014404:Tubulin; C462941:beta3 tubulin, mouse; D017493:Leukocyte Common Antigens