Human CD34+ cells differentiate into microglia and express recombinant therapeutic protein.
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.
Institut National de la Santé et de la Recherche Médicale U561, Hôpital Saint-Vincent de Paul, 75014 Paris, France.
Muriel
M
Asheuer
Françoise
F
Pflumio
Sonia
S
Benhamida
Anne
A
Dubart-Kupperschmitt
Françoise
F
Fouquet
Yoshinori
Y
Imai
Patrick
P
Aubourg
Nathalie
N
Cartier
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002493:Central Nervous System Diseases / Q000628:therapy; D005227:Fatty Acids / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D015870:Gene Expression; D049452:Green Fluorescent Proteins; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D017628:Microglia / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D036102:Peripheral Blood Stem Cell Transplantation; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014183:Transplantation, Heterologous
D018952:Antigens, CD34; D005227:Fatty Acids; D008164:Luminescent Proteins; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins