Human CD34+ cells differentiate into microglia and express recombinant therapeutic protein

被引:129
作者
Asheuer, M
Pflumio, FO
Benhamida, S
Dubart-Kupperschmitt, A
Fouquet, F
Imai, Y
Aubourg, P
Cartier, N [1 ]
机构
[1] Hop St Vincent de Paul, INSERM U561, F-75014 Paris, France
[2] Natl Inst Neurosci, Dept Neurochem, Tokyo, Japan
[3] Inst Cochin Genet Mol, INSERM U567, Dept Hematol, F-75014 Paris, France
关键词
D O I
10.1073/pnas.0306431101
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
In rodents, bone marrow-derived cells enter the brain during adult life. Allogeneic bone marrow transplantation is used to treat genetic CNS diseases, but the fate of human bone marrow and CD34(+) cells within the brain remains to be elucidated. The present study demonstrates that cells derived from human CD34(+) cells, isolated from either cord blood or peripheral blood, migrate into the brain after infusion into nonobese diabetic/severe combined immunodeficient mice. Both types of CD34(+)-derived cells differentiate into perivascular and ramified microglia. The lentiviral transfer of genes into CD34(+) cells before infusion does not modify the differentiation of human CD34(+) cells into microglia, allowing new transgenic proteins to be expressed in these cells. The transplantation of CD34(+) cells could thus be used for the treatment of CNS diseases.
引用
收藏
页码:3557 / 3562
页数:6
相关论文
共 32 条
[1]   Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning [J].
Aiuti, A ;
Slavin, S ;
Aker, M ;
Ficara, F ;
Deola, S ;
Mortellaro, A ;
Morecki, S ;
Andolfi, G ;
Tabucchi, A ;
Carlucci, F ;
Marinello, E ;
Cattaneo, F ;
Vai, S ;
Servida, P ;
Miniero, R ;
Roncarolo, MG ;
Bordignon, C .
SCIENCE, 2002, 296 (5577) :2410-2413
[2]   Maximal lentivirus-mediated gene transfer and sustained transgene expression in human hematopoietic primitive cells and their progeny [J].
Amsellem, S ;
Ravet, E ;
Fichelson, S ;
Pflumio, F ;
Dubart-Kupperschmitt, A .
MOLECULAR THERAPY, 2002, 6 (05) :673-677
[3]   Transduced CD34+ cells from adrenoleukodystrophy patients with HIV-derived vector mediate long-term engraftment of NOD/SCID mice [J].
Benhamida, S ;
Pflumio, F ;
Dubart-Kupperschmitt, A ;
Zhao-Emonet, JC ;
Cavazzana-Calvo, M ;
Rocchiccioli, F ;
Fichelson, S ;
Aubourg, P ;
Charneau, P ;
Cartier, N .
MOLECULAR THERAPY, 2003, 7 (03) :317-324
[4]   From marrow to brain: Expression of neuronal phenotypes in adult mice [J].
Brazelton, TR ;
Rossi, FMV ;
Keshet, GI ;
Blau, HM .
SCIENCE, 2000, 290 (5497) :1775-1779
[5]   RETROVIRAL-MEDIATED GENE-TRANSFER CORRECTS VERY-LONG-CHAIN FATTY-ACID METABOLISM IN ADRENOLEUKODYSTROPHY FIBROBLASTS [J].
CARTIER, N ;
LOPEZ, J ;
MOULLIER, P ;
ROCCHICCIOLI, F ;
ROLLAND, MO ;
JORGE, P ;
MOSSER, J ;
MANDEL, JL ;
BOUGNERES, PF ;
DANOS, O ;
AUBOURG, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (05) :1674-1678
[6]   Failure of bone marrow cells to transdifferentiate into neural cells in vivo [J].
Castro, RF ;
Jackson, KA ;
Goodell, MA ;
Robertson, CS ;
Liu, H ;
Shine, HD .
SCIENCE, 2002, 297 (5585) :1299-1299
[7]   Retroviral transfer and long-term expression of the adrenoleukodystrophy gene in human CD34+ cells [J].
Doerflinger, N ;
Miclea, JM ;
Lopez, J ;
Chomienne, C ;
Bougnères, P ;
Aubourg, P ;
Cartier, N .
HUMAN GENE THERAPY, 1998, 9 (07) :1025-1036
[8]   The neurobiology of X-linked adrenoleukodystrophy, a demyelinating peroxisomal disorder [J].
Dubois-Dalcq, M ;
Feigenbaum, V ;
Aubourg, P .
TRENDS IN NEUROSCIENCES, 1999, 22 (01) :4-12
[9]   Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice [J].
Eglitis, MA ;
Mezey, E .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (08) :4080-4085
[10]   Expression of the adrenoleukodystrophy protein in the human and mouse central nervous system [J].
Fouquet, F ;
Zhou, JM ;
Ralston, E ;
Murray, K ;
Troalen, F ;
Magal, E ;
Robain, O ;
DuboisDalcq, M ;
Aubourg, P .
NEUROBIOLOGY OF DISEASE, 1997, 3 (04) :271-285