Survival of neural precursor cells in growth factor-poor environment: implications for transplantation in chronic disease.
A key issue for therapeutic neural stem cell transplantation in chronic diseases is the long-term survival of transplanted cells in the brain. The normal adult central nervous system does not support the survival of transplanted cells. Presumably, the limited availability of trophic factors maintains the survival of resident cells but is insufficient for supporting the survival of transplanted cells. Specifically, in multiple sclerosis, a chronic relapsing disease, it would be necessary to maintain long-term survival of transplanted cells through phases of relapses and remissions. It may be beneficial to transplant cells as early as possible, in a form that will keep their survival independent of tissue support and ready for immediate mobilization upon tissue demand during disease relapse. In the present study, we examined whether, in the form of neurospheres, multipotential neural precursor cells (NPCs) survive in a growth factor-poor environment while maintaining their potential to respond to environmental cues. We found that after removal of growth factors from the culture medium of neurospheres in vitro, NPC proliferation decreased significantly, but most cells survived for a prolonged time and maintained their stem cell characteristics. After re-exposure to growth factors, neurosphere cells resumed proliferation and could differentiate along neural lineages. Furthermore, neurospheres, but not single NPCs, that were transplanted into the brain ventricles of intact animals survived within the ventricles for at least a month and responded to induction of experimental autoimmune encephalomyelitis and brain inflammation by extensive migration into the brain white matter and differentiated into glial lineage cells.
Einstein
Ofira
O
Department of Neurology, Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
Ben-Menachem-Tzidon
Ofra
O
Mizrachi-Kol
Rachel
R
Reinhartz
Etti
E
Grigoriadis
Nikolaos
N
Ben-Hur
Tamir
T
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival; D002908:Chronic Disease; D004777:Environment; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology*
D016222:Fibroblast Growth Factor 2