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Human CD34+ cells differentiate into microglia and express recombinant therapeutic protein
Muriel Asheuer1, Françoise Pflumio, Sonia Benhamida
1Institut National de la Santé et de la Recherche Médicale U561, Hôpital Saint-Vincent de Paul, 75014 Paris, France.
Summary
Human CD34(+) cells from cord or peripheral blood migrate to the brain and become microglia in mice. Gene-modified cells maintain their microglial fate, offering potential for central nervous system disease treatment.
Area of Science:
- Neuroscience
- Immunology
- Stem Cell Biology
Background:
- Bone marrow-derived cells can enter the brain in adult rodents.
- The fate of human bone marrow cells, particularly CD34(+) cells, in the brain is not fully understood.
- Allogeneic bone marrow transplantation is a potential therapy for genetic central nervous system (CNS) diseases.
Purpose of the Study:
- To investigate the migration and differentiation of human CD34(+) cells within the brain.
- To determine if gene modification affects the fate of human CD34(+) cells in the brain.
- To assess the potential of human CD34(+) cell transplantation for treating CNS diseases.
Main Methods:
- Isolation of human CD34(+) cells from cord blood and peripheral blood.
- Infusion of these cells into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice.
- Lentiviral gene transfer into CD34(+) cells prior to infusion.
- Analysis of cell differentiation and protein expression within the mouse brain.
Main Results:
- Human CD34(+) cells successfully migrated into the brain of recipient mice.
- Both cord blood and peripheral blood-derived CD34(+) cells differentiated into microglia (perivascular and ramified).
- Lentiviral gene transfer did not alter the microglial differentiation of human CD34(+) cells, enabling transgenic protein expression.
Conclusions:
- Human CD34(+) cells can effectively colonize the brain and differentiate into microglia.
- Gene-modified human CD34(+) cells retain their microglial differentiation potential.
- Transplantation of human CD34(+) cells, potentially gene-modified, shows promise for treating CNS disorders.