Embryonic and patient-specific induced pluripotent stem cells (iPSCs) hold great potential for cell-based therapies due to their ability to generate the tissues and cell types of developing organs.
In addition to embryonic stem cells (ESCs), some adult tissue-specific stem cells can also be potentially utilized for organ repair and therapeutic applications.
The continued advance of stem cell therapy in clinical medicine will require robust and renewable sources of stem cells. The origin of this source could be from ESCs, tissue-specific stem cells, or iPSCs. Since the only current source for the derivation of human embryonic stem cells (hESCs) remains discarded human tissue from in vitro fertilization (IVF) clinics, there is a close relationship between reproductive medicine and the field of stem cell biology. A continual supply of normal hESCs lines and iPSCs are essential to developing cell-based therapies to address general health concerns as well as those in reproductive medicine. Some of the potential target therapeutic applications in reproductive medicine include advancing treatments for oocyte development atresia diminishing gonadal function and urinary tract disorders associated with aging or premature ovarian failure.
In addition, there are less well-defined sources of stem cells from reproductive tissue such as ovarian stem cells and fetal stem cells that persist in maternal blood during fetal microchimerism, that might prove useful for cell-based therapies in health and reproductive function. In this chapter we briefly discuss some of the available types of stem cells and the clinical potential of this field.
Types of Stem Cells
ESCs were originally isolated from mouse, and hESCs are now derived from discarded human embryos from assisted reproductive technology (ART) clinics. The hallmark of hESCs is their ability to self-renew, proliferate on mitotically inactivated mouse embryonic fibroblast (MEF) feeders, and differentiate under permissive culture conditions into virtually any cell type of the human body. In the mouse model, the transfer of ESCs into a gestational carrier has demonstrated the ability of these cells to contribute to several tissue types as reflected by the birth of resultant chimeric mice, which can then go on to reproduce demonstrating germline contribution of these ESCs.
ESCs give rise to variety of cell types of the adult organism (ectoderm, mesoderm, and endoderm). Thus the potential applications of hESCs has captured the imagination of scientists and the medical community with the hope of developing cell-based therapies for diseases involving degenerative cellular mechanisms. The challenges to be met before achieving these hopes include (1) ethical issues, (2) evidence of chromosomal instability in culture, (3) concerns about antigen matching of donor cells, (4) concerns about possible teratoma formation post-transplant, and (5) concern for zoonoses given culturing techniques.
While the current literature has significantly concentrated on the potential of ESCs, there is a large population of stem cells or progenitor cells that are tissue specific and continue generating the progenitor cells even during adulthood which are called adult stem cells. In contrast to ESCs which are pluripotent, which can self-renew and potentially generate a broad range of tissue types from all three germ layers, ectoderm, mesoderm, and endoderm, the emerging data indicates that tissue-specific stem cells can be reprogrammed for development of various tissue types outside of the homotypic tissue by a process called transdifferentiation. Classic regenerative studies in amphibian development have demonstrated that tissue-specific progenitors are involved in repair of damaged organs by the transdifferentiation process.
The fact that the endometrial lining replenishes itself suggests the presence of a population of endometrial stem cells within the epithelium and stroma involved in the regenerative process of the endometrium. The identity and existence of such cells was initially confirmed by a functional assay transplanting such cells into host animals and growing endometrium. This population of cells is now suspected to have the capacity to not only form endometrium, but also potentially treat other disorders such as Parkinson disease. The injection of endometrial stem cells in the brains of mice with Parkinson symptoms suggests that these cells differentiate into dopaminergic cells to ameliorate such symptoms in the mice. Additionally, stromal stem cells have been isolated from the endometrium that are Stro-1 positive and have the ability to differentiate into various connective tissue such as bone and skin as well as participating in angiogenesis. Such results raise exciting possibilities for the therapeutic applications of these cells.