Survival and differentiation of pituitary colony forming cells in vivo

¹ Pituitary Research Unit, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia
² Bernard O'Brien Institute of Microsurgery and Department of Surgery, The University of Melbourne, St. Vincent's Hospital, Fitzroy, Victoria, Australia
³ School of Molecular & Biomedical Science, The University of Adelaide, South Australia, Australia

^* To whom correspondence should be addressed. E-mail: diana.lepore{at}mcri.edu.au.

	Abstract

Growth hormone (GH) deficiency is a significant clinical problem since growth hormone is essential for the regulation of growth, metabolism and the cardiovascular system. Stem and progenitor cells have been identified in many adult tissues. Recently our laboratory identified a cell type within the adult pituitary gland with stem cell-like properties which we have termed Pituitary Colony Forming Cells (PCFCs). Herein we investigate the ability of PCFCs to survive and differentiate in vivo. Enriched populations of PCFCs were transplanted into an in vivo micro-chamber model. Grafts were harvested at six weeks post-transplant and tested for surviving donor cells (LacZ(+)) or for differentiation (GH(+)). The results showed that donor cells survived in chambers (LacZ(+)) and underwent division (Phosphohistone-3-positive). Furthermore grafted cells showed co-localization of LacZ and GH, suggesting differentiation. To confirm differentiation, donor cells were obtained from a GH-eGFP reporter transgenic mouse model that expressed eGFP under control of the GH promoter. Cells that were eGFP(-), that is GH(-), were selected by FACS and transplanted. After six weeks eGFP(+)GH(+) cells were detected in grafts by immuno-staining and by FACS analysis of digested grafts. In conclusion PCFCs have the capacity to divide and differentiate into GH(+) cells in vivo. The vascularized tissue chamber model is an ideal model to investigate the environmental niche for PCFC expansion and differentiation and has the potential to be developed into a growth hormone releasing organoid in vivo.

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