Retrovirally transduced muscle-derived cells contribute to hematopoiesis at very low levels in the nonhuman primate model.
Recent studies have suggested a remarkable potential of adult stem cells from a variety of organs to give rise to cells of disparate organs, but evidence of such potential at a clonal level is lacking in most if not all studies to date. To assess directly the hematopoietic potential of muscle-derived cells in a relevant large animal, we initiated retroviral-tagging studies in the rhesus macaque to allow tracking at the clonal level by integration site analysis. Four rhesus macaques underwent transplantation with transduced muscle-derived cells after lethal irradiation followed by delayed infusion of an autologous hematopoietic graft. The first animal showed no evidence of hematopoietic recovery and, despite infusion of the backup hematopoietic graft, succumbed due to complications of prolonged cytopenias. In the remaining three animals, the overall contribution of retrovirally tagged muscle-derived cells toward hematopoiesis was exceedingly low. Retroviral integration site analysis among clonally derived muscle cells and bone marrow cells in vivo in one animal suggests a common source. These results demonstrate that harvesting disparate organs for cellular therapy is currently highly inefficient at best.
Gao
Chunji
C
Molecular and Clinical Hematology Branch, National Institute of Diabetes and Digestive and Kidney Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA.
Kang
Elizabeth M
EM
Kuramoto
Ken
K
Agricola
Brian A
BA
Metzger
Mark
M
von Kalle
Christof
C
Donahue
Robert E
RE
Tisdale
John F
JF
D000818:Animals; D005822:Genetic Vectors; D006410:Hematopoiesis / Q000235:genetics* / Q000502:physiology; D008253:Macaca mulatta; D032342:Muscle Cells / Q000502:physiology* / Q000637:transplantation; D016133:Polymerase Chain Reaction; D012190:Retroviridae; D013997:Time Factors; D014161:Transduction, Genetic; D016662:Virus Integration / Q000235:genetics