Gene transfer into nonhuman primate CD34+CD11b-bone marrow progenitor cells capable of repopulating lymphoid and myeloid lineages
article
We investigated whether rhesus monkey CD34+CD11b-hematopoietic stem cells can be transduced with recombinant retroviruses carrying the human adenosine deaminase (hADA) gene by co-cultivation with a virus-producing cell line. Following autologous transplantation, polymerase chain reaction (PCR) analysis on peripheral blood mononuclear cells and granulocytes showed that the hADA-retrovirus was present in approximately 0.1% of the cells for at least 400 days post transplantation in 2 monkeys. Bone marrow that was harvested 16 months after transplantation carried ADA-overexpressing myeloid progenitor cells capable of in vitro colony formation. In addition, hADA activity could be demonstrated in T lymphocytes that were harvested 9 months post transplantation. Thus, in vitro transduction of CD34+CD11b-cells led to long-term repopulation of the hematopoietic system with transduced cells of lymphoid and myeloid lineages expressing the hADA gene. To investigate whether infusion of virus-producing cells into a rhesus monkey undergoing autologous bone marrow transplantation could lead to in vivo transfer of the recombinant retrovirus, 1 monkey was infused with CD34+CD11b-bone marrow cells (BMC) and a large quantity of virus-producing cells. Few provirus-carrying cells could temporarily be detected in this animal. This shows that in vivo gene transfer into a regenerating hemopoietic system can occur, albeit at very low efficiency.
Topics
Cd11b antigenCd34 antigenAnimal cellAutologous bone marrow transplantationBone marrowCell cultureCell lineageControlled studyGene transferGenetic transductionGranulocyteHematopoietic stem cellLymphoid cell lineNonhumanPolymerase chain reactionPromyelocyteRetrovirusRhesus monkeyT lymphocyteVirus recombinantAdenosine DeaminaseAnimalAntigens, CDAntigens, CD11Antigens, CD34Cell DifferentiationCell LineDNA ReplicationGene Transfer TechniquesHematopoietic Stem Cell TransplantationHematopoietic Stem CellsHumanMacaca mulattaT-LymphocytesAnimaliaMacaca mulattaPrimatesUnidentified retrovirusAdenosine Deaminase, EC 3.5.4.4
TNO Identifier
280591
ISSN
1043-0342
Source
Human Gene Therapy, 5(3), pp. 295-305.
Pages
295-305
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