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Behavior of hippocampal stem/progenitor cells following grafting into the injured aged hippocampus
Author(s) -
Shetty Ashok K.,
Rao Muddanna S.,
Hattiangady Bharathi
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21764
Subject(s) - hippocampal formation , neurosphere , hippocampus , neural stem cell , progenitor cell , biology , embryonic stem cell , neuroscience , transplantation , neurogenesis , stem cell , microbiology and biotechnology , neuroepithelial cell , adult stem cell , medicine , genetics , gene
Multipotent neural stem/progenitor cells (NSCs) from the embryonic hippocampus are potentially useful as donor cells to repopulate the degenerated regions of the aged hippocampus after stroke, epilepsy, or Alzheimer's disease. However, the efficacy of the NSC grafting strategy for repairing the injured aged hippocampus is unknown. To address this issue, we expanded FGF‐2‐responsive NSCs from the hippocampus of embryonic day 14 green fluorescent protein–expressing transgenic mice as neurospheres in vitro and grafted them into the hippocampus of 24‐month‐old F344 rats 4 days after CA3 region injury. Engraftment, migration, and neuronal/glial differentiation of cells derived from NSCs were analyzed 1 month after grafting. Differentiation of neurospheres in culture dishes or after placement on organotypic hippocampal slice cultures demonstrated that these cells had the ability to generate considerable numbers of neurons, astrocytes, and oligodendrocytes. Following grafting into the injured aged hippocampus, cells derived from neurospheres survived and dispersed, but exhibited no directed migration into degenerated or intact hippocampal cell layers. Phenotypic analyses of graft‐derived cells revealed neuronal differentiation in 3%–5% of cells, astrocytic differentiation in 28% of cells, and oligodendrocytic differentiation in 6%–10% cells. The results demonstrate for the first time that NSCs derived from the fetal hippocampus survive and give rise to all three CNS phenotypes following transplantation into the injured aged hippocampus. However, grafted NSCs do not exhibit directed migration into lesioned areas or widespread neuronal differentiation, suggesting that direct grafting of primitive NSCs is not adequate for repair of the injured aged brain without priming the microenvironment. © 2008 Wiley‐Liss, Inc.