Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 2002 Jul 4;418(6893):41-9. PubMed.
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University of Central Florida
The Verfaillie paper reports the identification of pluripotent adult stem cells, which may serve as an alternative to embryonic stem cells as transplant material for cell replacement therapy. Although the paper's title refers to this cell as equivalent to mesenchymal stem cells, it could provide progenitors for mesenchymal and hematopoietic cells. The multipotency of mesenchymal stem cells has been discussed for a long time.
This report details a series of extensive studies from in vitro to in vivo. The characteristics and functions of a sub-population of bone marrow stem cells are quite similar to those of embryonic stem cells in that they responded to treatment with the same factors in vitro. This suggests that the "multipotent adult progenitor cells" did not differentiate to tissue-specific stem cells by responding to the environment or that adult bone marrow has environmental conditions similar to the inside of the blastocyst. Curiously, the cells did not develop a typical neural differentiation after transplantation to the postnatal animal. Since factors needed for neurogenesis may continue to be expressed in the postnatal animal, this issue needs to be explained. In summary, these cells have great potential, but I would like future studies to show their neural differentiation in the adult brain in before "multipotent adult progenitor cells" are applied to neuroreplacement strategies.
The McKay article pushes the envelope of embryonic stem cells in neuroreplacement strategies further. This study has overcome two hurdles: it differentiated embryonic stem cells into neural cells, and it generated from these a specific type of neuron (dopaminergic). Each experiment elegantly proceeds from in vitro differentiation to the assessment of in vivo physiological function including a behavioral test.
Transplanted cells survived for 8 weeks without changing their numbers, indicating no tumorigenesis. I like the idea of transfecting Nurr-1into embryonic stem cells, a transcription factor that induces dopaminergic differentiation in midbrain precursor cells. This approach may be useful to induce other specific types of differentiation in the stem cells.
The only down side I see with this study is that they transplanted the cell into the striatum, the projection area of the dopaminergic cells in the substantia nigra (SN). To aim at full integration of the transplanted cell into the host brain, neuroreplacement ultimately has to be done in SN. Otherwise, cells transplanted to the striatum may become uncontrolled and cause side effects, as we have seen in several fetal tissue transplant studies. I would like to see SN cell replacement and a trial with other types of stem cell using similar tactics in the future.
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