Positive influence of long-term growth hormone therapy on circulating stem cells in pediatric patients with growth hormone deficiency

Very small embryonic/epiblast-like stem cells (VSELs), present in circulating blood, are small, non-hematopoietic cells that express markers of pluripotent embryonic and primordial germ cells. VSELs are believed to contribute to postnatal tissue and organ regeneration. We report the first long-term observation of VSELs in response to growth hormone (GH) therapy in pediatric patients. Twenty patients aged 5.2-13.4 years with GH-deficiency were monitored periodically during the first year of GH treatment. Eight of these patients were re-examined after eight years of continuous therapy. Selected stem cell populations were analyzed in peripheral blood using flow cytometry. Long-term GH therapy resulted in increased numbers of CD34 + VSELs, while CD133 + VSELs remained comparable to baseline. The increase in VSELs was accompanied by parallel increases in circulating hematopoietic stem cells, mesenchymal stromal cells (MSCs), and endothelial progenitor cells. We observed significant positive correlations between VSELs and MSCs, and between CD34 + VSELs and MSCs with postprandial glucose levels. These data suggest that VSELs are responsive to GH treatment. Long-term GH therapy appears to modulate VSEL populations without causing harm and may even enhance them in GH-deficient patients. Unlike findings in experimental animals, GH therapy in humans did not show adverse effects on lifespan or organ function.