Long-term treatment with recombinant human growth hormone in pediatric patients with growth hormone deficiency influences but does not destroy stem cells circulating in blood

Abstract Very small embryonic/epiblast-like stem cells (VSELs), found in circulating blood are small, non-hematopoietic cells expressing markers of pluripotent embryonic and primordial germ cells. VSELs are responsible for postnatal tissue and organ rejuvenation. For the first time we performed long-term observations of VSELs in response to growth hormone (GH) therapy in pediatric patients. Enrolled 20 patients aged 5.2–13.4 with GH-deficiency were monitored periodically for first year of GH treatment. Eight of them were examined again after eight years of continuous GH therapy. Selected stem cells were analyzed in peripheral blood flow cytometrically. The number of 34 + VSELs was higher than baseline and the number of 133 + VSELs was comparable to the baseline number after long-term therapy. The increase in VSELs number paralleled the increase in circulating hematopoietic stem cells, mesenchymal stem cells (MSCs) and endothelial progenitor cells. We found a significant, positive correlation between VSELs and MSCs, moreover both 34 + VSELs and MSCs positively correlated with postprandial glucose. Our data confirm that VSELs respond to GH treatment. Long-term therapy with GH modulates but did not damage, even improves the population of VSELs in GH-deficient patients. Therefore in contrary to experimental animals GH therapy seems not damage life span and organ rejuvenation in patients.