Influence of telomere length on short-term recovery after allogeneic stem cell transplantation

Abstract

Telomeres shorten in somatic cells during aging and states of increased turnover, including hematopoietic stem cell transplantation. Fast hematopoietic recovery is critical for the patients' course after hematopoietic stem cell transplantation. It is unknown whether telomere length in hematopoietic stem cells (HSCs) predicts short-term hematopoietic recovery. We quantified telomere length by flow fluorescence in situ hybridization analysis in HSCs and granulocytes of healthy stem cell donors and monitored time to peripheral blood cell recovery in transplanted hosts. Furthermore, we measured in vitro repopulation potency of HSCs by assaying for colony-forming units granulocyte-macrophage (CFU-GM). Telomere length in HSC shortens continuously in vivo and is comparable to telomere length in granulocytes from the same individual. Numbers of in vitro formed CFU-GM per HSC show an inverse relationship to age and telomere length. However, telomere length in HSCs was not correlated with short-term recovery after HSC transplantation. These findings suggest that healthy stem cell donors have sufficient telomere length reserve to repopulate a myeloablatively treated host, despite continuous aging of HSCs in vivo and decreased repopulation ability of HSCs from older donors in vitro.