Abstract:
:Hematopoietic bone marrow stem cells generate differentiated blood cells and, when transplanted, may contribute to other organs, such as the brain, heart, and liver. An understanding of in vivo clonal behavior of stem cells will have important implications for cellular and gene therapy. For the first time, we have directly demonstrated the derivation of circulating peripheral blood cells from individual stem cell clones. We analyzed the clonal composition of retrovirus-marked peripheral blood leukocyte populations in 2 different primate models by a novel direct genomic sequencing technique allowing the identification of vector insertion sites. More than 80 contributing long-term hematopoietic clones were identified in individual rhesus macaque peripheral blood transplant recipients and more than 25 different clones in a baboon marrow transplant recipient. Up to 5 insertion sequences from each animal were used to trace the long-term contribution of stem cell clones in these primate models. Continuous and mostly pluripotent contributions of peripheral blood leukocytes from each of the traced clones could be detected for the entire follow-up period of 23 to 33 months. Our study provides direct molecular evidence for a polyclonal, multilineage, and sustained contribution of individual stem cells to primate hematopoiesis.
journal_name
Bloodjournal_title
Bloodauthors
Schmidt M,Zickler P,Hoffmann G,Haas S,Wissler M,Muessig A,Tisdale JF,Kuramoto K,Andrews RG,Wu T,Kiem HP,Dunbar CE,von Kalle Cdoi
10.1182/blood-2002-02-0407subject
Has Abstractpub_date
2002-10-15 00:00:00pages
2737-43issue
8eissn
0006-4971issn
1528-0020journal_volume
100pub_type
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