Abstract

The goal of the intense research on stem cells is for human application. Recently, knowledge of stem cells has progressed rapidly and experimental therapies are already in clinical trials. However, for more far reaching application and successful therapy much more remains to be learned about stem cells. There are many more questions than answers. What is a stem cell? What different kinds are there? Can they be obtained and manipulated? What are the lineages that derive from stem cells, and how plastic are cells in a lineage? Are there circulating stem cells in adults? Do they participate in repair of injury? What type of stem cell is most appropriate for a given clinical application? New technologies need to be developed to apply to stem cells for effective gene delivery. What role, if any, does fusion of stem cells play in tissue regeneration? Can the differentiation potential of stem cells at different stages of determination be used to select cells for specific clinical applications? What are the signals that recruit, activate, and induce differentiation in stem cells? What are the signaling pathways for activation and differentiation of stem cells, and can they be manipulated to advantage? How can stem cells be used to understand carcinogenesis and developmental abnormalities? Are embryonic stem cells, which have the potential to produce progeny that can differentiate into any adult tissues the best cells for therapeutic use? Or in some instances, are adult stem cells resident in adult tissues or circulating adult bone marrow derived cells a better choice? How can immune rejection of transplanted cells be avoided or prevented? Will therapeutic cloning, whereby transfer of somatic nuclei to provide an embryonic cell line that matches the patient, become clinically applicable? Can embryonic germ cells be used to greater advantage that embryonic stem cells? Will adult stem cells, if they can be isolated and cultured, be a better choice for selected use, for example, in replacing cells in a specific damaged organ. Are there adult multipotent stem cells or can adult tissue-determined stem cells transdifferentiate to another tissue cell type? If so, how can this be controlled? Does fusion play a role in functional stem cell plasticity and can a way to use fusion to direct tissue repair or replacement be devised? Do human somatic cells have the capacity for dedifferentiation, such as found during regeneration of tissues in amphibians? Can this phenomenon be applied to mammalian tissues and eventually used clinically? How can genetic modification of human embryonic or adult stem cells be improved and applied? The potential of stem cell therapy has great promise and is only limited by our incomplete knowledge of what stem cells are and how they function.

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