ESPE Abstracts

Objective: Very small embryonic/epiblast‐like stem cells (VSELs), found in human bone marrow and other adult tissues, also 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. It was reported that VSELs decreased after prolonged GH or IGF-1 administration in experimental animals and after prolonged IGF-1 administration in human subjects.

Design: For the first time we performed long-term observations of these populations of cells in response to recombinant human GH (rhGH) therapy in pediatric patients.

Methods: Twenty five patients treated with GH, twenty with GH-deficiency, three with Turner Syndrome and two with Prader-Willi Syndrome in the age of 5.04-13.37 years were included in the study. Fasting blood samples for measurement of populations of circulating stem cells and some biochemical parameters were taken before the introduction of GH treatment, and then two weeks, one month, three months, six months and eight years after it. Subsequently, we evaluated by employing FACS changes in the number of circulating in peripheral blood (PB) small CD133⁺Lin^-CD45^- VSELs and CD34⁺Lin^-CD45^- VSELs and moreover long term repopulating hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs). Statistical analysis was performed using ANOVA with post-hoc Tukey’s test. Each-other correlations between cells populations and hormonal and metabolic parameters were evaluated using multiple regression analysis.

Results: The number of 34+VSELs, after a temporary decline in first month of therapy with rhGH, reached a higher level after 8 years of treatment in GH-deficient patients and similar in the rests, the number of 133+VSELs after long-term therapy was comparable to the baseline number. The increase in VSELs number paralleled the increase in circulating HSCs, MSCs, and EPCs. There was a strong positive correlation between the SDS of patients’ height and 34+VSEls number and negative correlation between 133+HSCs and SDS of patients’ height. We found a significant, positive correlation between VSELs and MSCs and moreover both 34+VSELs and MSCs positively correlated with postprandial glucose.

Conclusions: Our data confirm that VSELs respond to GH treatment. Long-term therapy with rhGH modulates but did not damage the population of VSELs, even improves it in GH-deficient patients. Therefore, in contrary to experimental animals GH therapy seems not robust life span in patients. Our findings could confirm an important role of VSELs in process of growing regulated by GH, not with the participation of IGF-1 but with insulin signaling.