Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains

Proceedings of the National Academy of Sciences of the United States of America - Tập 96 Số 19 - Trang 10711-10716 - 1999
Gene Kopen1, Darwin J. Prockop1, Donald G. Phinney1
1Center for Gene Therapy, MCP Hahnemann University, 245 North 15th Street, Philadelphia, PA 19102-1192

Tóm tắt

Stem cells are a valuable resource for treating disease, but limited access to stem cells from tissues such as brain restricts their utility. Here, we injected marrow stromal cells (MSCs) into the lateral ventricle of neonatal mice and asked whether these multipotential mesenchymal progenitors from bone marrow can adopt neural cell fates when exposed to the brain microenvironment. By 12 days postinjection, MSCs migrated throughout the forebrain and cerebellum without disruption to the host brain architecture. Some MSCs within the striatum and the molecular layer of the hippocampus expressed glial fibrillary acidic protein and, therefore, differentiated into mature astrocytes. MSCs also populated neuron rich regions including the Islands of Calleja, the olfactory bulb, and the internal granular layer of the cerebellum. A large number of MSCs also were found within the external granular layer of the cerebellum. In addition, neurofilament positive donor cells were found within the reticular formation of the brain stem, suggesting that MSCs also may have differentiated into neurons. Therefore, MSCs are capable of producing differentiated progeny of a different dermal origin after implantation into neonatal mouse brains. These results suggest that MSCs are potentially useful as vectors for treating a variety of central nervous system disorders.

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Tài liệu tham khảo

10.1038/292154a0

10.1073/pnas.78.12.7634

10.1071/RD9940543

10.1146/annurev.cb.11.110195.000343

10.1242/dev.106.4.619

10.1016/S0092-8674(00)81867-X

10.1073/pnas.94.8.4080

10.1073/pnas.95.7.3908

10.1242/jcs.1988.Supplement_10.5

10.1002/(SICI)1097-4644(1998)72:30/31 <73::AID-JCB11>3.0.CO;2-L

10.1126/science.283.5401.534

10.1002/(SICI)1097-4644(19990315)72:4<570::AID-JCB12>3.0.CO;2-W

10.1073/pnas.92.25.11879

10.1006/excr.1997.3858

10.1126/science.276.5309.71

K Talbot, N J Woolf, L L Butcher J Comp Neurol 275, 533–579 (1988).

10.1002/cne.901370404

10.1126/science.8178174

10.1002/cne.901790104

10.1002/cne.902310105

10.1146/annurev.ne.18.030195.002125

10.1523/JNEUROSCI.17-13-05046.1997

10.1073/pnas.90.5.2074

10.1016/S0166-2236(96)10035-7

10.1016/0896-6273(92)90216-Z

10.1523/JNEUROSCI.15-11-07238.1995

10.1523/JNEUROSCI.16-08-02649.1996

10.1016/0165-3806(90)90240-Y

10.1523/JNEUROSCI.16-03-01091.1996

P F Bartlett, L R Richards, T J Kilpatrick, P T Talman, K A Bailey, G J Brooker, R Dutton, S A Koblar, V Nurcombe, M O Ford Ciba Found Symp 193, 85–99 (1995).

10.1016/S0169-328X(97)00065-X

10.3109/08977199009043907

R M Locklin, M C Williamson, J N Beresford, J T Triffitt, M E Owen Clin Orthop Relat Res 313, 27–35 (1995).

10.1006/bcmd.1995.0011

J Fang, B K Hall Int J Dev Biol 39, 519–528 (1995).

Q-R Wang, N S Wolf Exp Hematol 18, 355–359 (1990).

W E Modderman, T Vrijheid-Lammers, C W Lowik, P J Nijweide Exp Hematol 22, 194–201 (1994).

10.1182/blood.V84.3.753.753

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Proceedings of the National Academy of Sciences of the United States of America

Tập 96 Số 19

10711-10716

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