人类CD34+细胞分化为小胶质细胞并表达重组治疗性蛋白。
Human CD34+ cells differentiate into microglia and express recombinant therapeutic protein.
作者信息
Asheuer Muriel, Pflumio Françoise, Benhamida Sonia, Dubart-Kupperschmitt Anne, Fouquet Françoise, Imai Yoshinori, Aubourg Patrick, Cartier Nathalie
机构信息
Institut National de la Santé et de la Recherche Médicale U561, Hôpital Saint-Vincent de Paul, 75014 Paris, France.
出版信息
Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3557-62. doi: 10.1073/pnas.0306431101. Epub 2004 Feb 27.
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.
在啮齿动物中，成年期骨髓来源的细胞会进入大脑。同种异体骨髓移植用于治疗遗传性中枢神经系统疾病，但人类骨髓和大脑内CD34(+)细胞的命运仍有待阐明。本研究表明，从脐带血或外周血中分离出的人类CD34(+)细胞来源的细胞，在注入非肥胖糖尿病/严重联合免疫缺陷小鼠后会迁移到大脑中。这两种类型的CD34(+)细胞来源的细胞都会分化为血管周围和分支状的小胶质细胞。在注入前将基因慢病毒转移到CD34(+)细胞中，并不会改变人类CD34(+)细胞向小胶质细胞的分化，从而使新的转基因蛋白能够在这些细胞中表达。因此，CD34(+)细胞的移植可用于治疗中枢神经系统疾病。
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