Circumstantial evidence has accumulated over the last decade that there are pluripotent stem cells in the hippocampus of humans and other animals. Much hope has been attached to these heretofore elusive cells because they might be induced to grow, in vitro, into hippocampal neurons to replace those lost to pathological processes like Alzheimer's disease. Now, the first good evidence that such cells are there-and can be extracted surgically and induced to differentiate into neurons-has been published in the March issue of Nature Medicine.
Steven Goldman, Neeta Roy, and their colleagues at Cornell Medical School used tissue gathered during temporal lobe resections for conditions such as epilepsy or cancer. They picked out progenitor cells by transfecting dentate gyrus cells in culture with markers for proteins expressed during early stages of the neuronal lineage. These cells then proliferated in a growth factor-supplemented medium and eventually produced neurons, as indicated by the presence of mature neuron protein markers, and by electrophysiological evidence of calcium and sodium channel activity.
If this technique can be refined, write Jack Antel and his colleagues from McGill University, Montreal, in a News and Views article in the same issue, there is the possibility that biopsies from Alzheimer's patients could produce progenitor cells that could be reintroduced as hippocampal neurons. This would get around other stem cell approaches such as the use of fetal cells, with its attendant controversies, and transplants of healthy cells from donors, which bring in various host-graft compatibility problems. However, they also point out that there are still a host of questions to be answered before such a therapy could be initiated. Among them: How long can these cells be maintained in culture? Do they in fact have the capability of becoming true hippocampal cells and being integrated into existing networks? And once implanted, would such cells become victims of the ongoing disease process?—Hakon Heimer
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- Roy NS, Wang S, Jiang L, Kang J, Benraiss A, Harrison-Restelli C, Fraser RA, Couldwell WT, Kawaguchi A, Okano H, Nedergaard M, Goldman SA. In vitro neurogenesis by progenitor cells isolated from the adult human hippocampus. Nat Med. 2000 Mar;6(3):271-7. PubMed.
- Antel JP, Nalbantoglu J, Olivier A. Neuronal progenitors-learning from the hippocampus. Nat Med. 2000 Mar;6(3):249-50. PubMed.