Grand challenges in the field of stem cell research.

Abstract

DISCOVERY OF ADULT STEM CELLS In 1961, Mauro first discovered that skeletal muscle fibers of frogs contain mononuclear cells underneath the basal lamina by electron microscope and termed these “satellite cells” (Mauro, 1961). By contrast, they failed to find any satellite-like cells in cardiac muscle after thorough search of electron micrographs. Since then, satellite cells have been confirmed to be a true stem cell for skeletal muscle (von Maltzahn et al., 2013). Adult skeletal muscle possesses extraordinary regeneration capability (Seale and Rudnicki, 2000). After exercise or muscle injury, large numbers of new muscle fibers are normally formed within a week because of expansion and differentiation of muscle satellite cells as a stem cell population for muscle regeneration. In the same year, Till and McCulloch first established the concept of stem cells using bone marrow transplantation into irradiated mice (Till and McCulloch, 1961; Armstrong et al., 2012). They found that donorderived hematopoietic stem cells (HSCs) or progenitor cells can be colonized in the recipient spleen after transplantation. A single colony can give rise to multiple hematopoietic lineages as well as stem or progenitor cells, indicating the multipotent differentiation and self-renewal abilities for the HSCs or progenitor cells. In the last two decades, experiments have established the existence of adult stem cells in most tissues that appear to have the ability to differentiate into specific cell types following injury as a means of regeneration in vivo (Barker et al., 2010). For example, neural stem cells (NSCs) from the central nervous system can generate multiple neural cell types to respond (Gage and Temple, 2013). Bone marrow contains two distinct stem cell types: marrow stromal cells and HSCs. HSCs possess their ability to produce all blood cell lineages (Ugarte and Forsberg, 2013). Multipotent mesenchymal stem cells derived from marrow stromal cells can differentiate into a wide variety of cell lineages, including skeletal muscle, neurons, and hematopoietic cells in vitro and following transplantation (Pittenger et al., 1999; Dimarino et al., 2013). Therefore, many or all tissues may contain a population of stem cells that can differentiate in an appropriate manner in response to the growth factors and signals provided by their host tissues. The current challenge is to understand the molecular mechanisms of how these adult stem cells maintain their stem cell qualities: specific differentiation capability, self-renewal activity, and response to the microenvironments of the stem cell niche.