In vivo telomere dynamics of human hematopoietic stem cells

AUTOR(ES)

Notaro, Rosario

FONTE

The National Academy of Sciences of the USA

RESUMO

Aging in vivo and cell division in vitro are associated with telomere shortening. Several lines of evidence suggest that telomere length may be a good predictor of the long term replicative capacity of cells. To investigate the natural fate of chromosome telomeres of hematopoietic stem cells in vivo, we measured the telomere length of peripheral blood granulocytes from 11 fully engrafted bone marrow transplant recipients and from their respective donors. In 10 of 11 donor–recipient pairs, the telomere length was significantly reduced in the recipient and the extent of reduction correlated inversely with the number of nucleated cells infused. These data provide internally controlled in vivo evidence that, concomitantly with their proliferation, hematopoietic stem cells lose telomere length; it is possible that, as a result, their proliferative potential is reduced. These findings must be taken into account when developing new protocols in which few stem cells are used for bone marrow transplantation or for gene therapy.

Documentos Relacionados

• Wnt-5A augments repopulating capacity and primitive hematopoietic development of human blood stem cells in vivo
• Retrovirus-mediated gene transfer of human adenosine deaminase: expression of functional enzyme in murine hematopoietic stem cells in vivo.
• RevM10-expressing T cells derived in vivo from transduced human hematopoietic stem-progenitor cells inhibit human immunodeficiency virus replication.
• Dissociation of telomerase activity and telomere length maintenance in primitive human hematopoietic cells
• Sustained ex vivo expansion of hematopoietic stem cells mediated by thrombopoietin