Lineage-restricted neural precursors survive, migrate, and differentiate following transplantation into the injured adult spinal cord.
Fetal spinal cord from embryonic day 14 (E14/FSC) has been used for numerous transplantation studies of injured spinal cord. E14/FSC consists primarily of neuronal (NRP)- and glial (GRP)-restricted precursors. Therefore, we reasoned that comparing the fate of E14/FSC with defined populations of lineage-restricted precursors will test the in vivo properties of these precursors in CNS and allow us to define the sequence of events following their grafting into the injured spinal cord. Using tissue derived from transgenic rats expressing the alkaline phosphatase (AP) marker, we found that E14/FSC exhibited early cell loss at 4 days following acute transplantation into a partial hemisection injury, but the surviving cells expanded to fill the entire injury cavity by 3 weeks. E14/FSC grafts integrated into host tissue, differentiated into neurons, astrocytes, and oligodendrocytes, and demonstrated variability in process extension and migration out of the transplant site. Under similar grafting conditions, defined NRP/GRP cells showed excellent survival, consistent migration out of the injury site and robust differentiation into mature CNS phenotypes, including many neurons. Few immature cells remained at 3 weeks in either grafts. These results suggest that by combining neuronal and glial restricted precursors, it is possible to generate a microenvironmental niche where emerging glial cells, derived from GRPs, support survival and neuronal differentiation of NRPs within the non-neurogenic and non-permissive injured adult spinal cord, even when grafted into acute injury. Furthermore, the NRP/GRP grafts have practical advantages over fetal transplants, making them attractive candidates for neural cell replacement.
Lepore
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AC
Department of Neurobiology and Anatomy, 2900 Queen Lane, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
Fischer
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I
D000469:Alkaline Phosphatase / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D015415:Biomarkers / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D005260:Female; D006085:Graft Survival / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism / Q000601:surgery; D013119:Spinal Cord Injuries / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
D015415:Biomarkers; D000469:Alkaline Phosphatase