Commonalities in the endocrinology of stem cell biology and organ regeneration

Abstract

A c c e p t e d M a n u s c r i p t 2 'If it is not broken, do not try to fix it' is an adage that lauds the occasional virtue of inactivity.However, for most, if not all, of the human body's organs and tissues there is no such rest. All of the two hundred plus different cell-types within the human body constantly require careful attention to maintain optimal function. The longevity of our lives, far greater than the lifespan of most single cells, brings with it a requirement for continual tissue and organ regeneration, where cell loss is perfectly matched by cell replacement; continual 'breaking' that necessitates 'fixing' on a day-to-day, month-tomonth and year-to-year basis. This issue of Molecular & Cellular Endocrinology examines the mechanisms underlying this process for a range of organs, both in health and disease coupled to the potential for selected cell replacement therapies.The project set out with the goal of bringing together a range of articles examining the role of hormones and growth factors on stem or progenitor cells and their progeny in endocrine organs and other hormone-relevant sites (Table 1). The result is ten articles (Berry et al., 2008;Gargett et al., 2008;Garrett and Emerson, 2008;Gray, 2008;Hanley et al., 2008;Hoffman, 2008;Ishizuya-Oka and Shi, 2008;Kristensen et al., 2008;Paus et al., 2008;Rowland and Brubaker, 2008) that should be considered alongside a previous review in Molecular & Cellular Endocrinology on the regeneration of the adrenal cortex from resident stem cells (Kim and Hammer, 2007). To complement these in vivo paradigms, three examples are included here of current in vitro stem cell work aiming to generate terminally differentiated cell-types for clinical therapy (Best et al., 2008;Moore et al., 2008;Tare et al., 2008): an endocrine twist on cell therapy meets regenerative biology. The outcome underlines mechanistic themes with the potential for new research driven by extrapolation across otherwise distinct locations. One emergent thread running through many of the articles is the critical importance of microenvironment-the 'niche', comprised of stem or progenitor cells in vascularised biological matrices that respond selectively to a range of intercellular signals depending upon, amongst other factors, cell receptor expression. Correct assembly of the niche permits healthy organs and tissues that Page 3 of 15 A c c e p t e d M a n u s c r i p t 3 continually regenerate without scarring, and offers the blueprint for ex vivo tissue engineering. Other articles describe dysplastic or aberrant construction as a potentially causative factor in a range of disorders and diseases from epilepsy to cancer.In some locations, such as the central nervous system (CNS) (Gray, 2008) and pancreas , the presence of clearly defined adult stem cells or progenitors remains contentious.However, for these organs it is still possible to discern microenvironments, either in situ or once cells have been taken in vitro, where a regenerative capacity seems feasible. Here, author teams have been ...

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