ABSTRACT
Understanding the mechanisms behind adult stem cell support of tissue function is of extreme importance when considering next-generation methods to treat damaged or diseased organs in humans. Two general translational approaches have been taken with adult stem cells in order to speed their introduction into the clinic. First, the understanding of the basal function(s) of endogenous adult stem cells has led to strategies to stimulate these cells into improved tissue support and repair. Protecting these cells from damage caused by disease – or damage caused by the treatment of disease – is a critical consideration. Secondly, adult stem cells are being coaxed to behave differently than their endogenous roles in the body. Such strategies seek to use nonessential biopsied cells to produce or protect the cells of their source organ or even completely unrelated tissues. A general paradigm for these two modes of use of stem cells may be seen in the cases of bone marrow-resident stem cells, hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). HSCs are routinely extracted from donors or patients themselves within bone marrow biopsies or mobilized stem cell blood products, and redelivered for therapy. More recently, attempts are being made to stimulate these cells via drug or biomolecule treatment to modulate the production of blood and other hematopoietic lineages within the clinic. Advances in the handling of both HSCs and MSCs have allowed for the directed differentiation of these cell types into cells that may contribute to peripheral
organs (e.g. endothelial cells from HSCs and various stromal support cells from MSCs) (See References 1-3 for reviews.)
As evidenced by this book, stem cells are now viewed as potential therapeutic tools for the treatment of reproductive tract disease and/or infertility. This chapter considers the special case of ovarian failure in females, due to the natural loss or destruction of the pool of oocytes within the ovary. If, indeed, new oocytes are produced by stem cells during adult life by circulating progenitor cells,4 the ovary may be a uniquely tractable model for the study of stem cell support of other organs. After all, oocytes in mammalian ovaries generally number in the few thousands in rodents and the tens of thousands in young humans, and that number only declines with advancing age. And it is relatively easy, if time consuming, to accurately measure the actual number of oocytes in the ovary at any given time or after experimental treatments.5,6 Thus, the exact numerical contribution of a pool of stem cells to a tractable pool of differentiated cells (e.g. oocytes) can be measured. Perhaps more general mechanisms of stem cell support of other tissues will be uncovered by the study of these processes affecting oocyte number and thereby ovary function.
