Stem cells have emerged as a key element of regenerative medicine therapies due to their inherent ability to differentiate into a variety of cell phenotypes, thereby providing numerous potential cell therapies to treat an array of degenerative diseases and traumatic injuries. A recent paradigm shift has emerged suggesting that the beneficial effects of stem cells may not be restricted to cell restoration alone, but also due to their transient paracrine actions. Stem cells can secrete potent combinations of trophic factors that modulate the molecular composition of the environment to evoke responses from resident cells. Based on this new insight, current research directions include efforts to elucidate, augment and harness stem cell paracrine mechanisms for tissue regeneration. This article discusses the existing studies on stem/progenitor cell trophic factor production, implications for tissue regeneration and cancer therapies, and development of novel strategies to use stem cell paracrine delivery for regenerative medicine.
Keywordscancer; immune modulation; paracrine actions; stem cells; tissue regeneration; trophic factors Regenerative medicine therapies, fueled by advances in stem cell biology and technologies, seek to direct inherent nonhealing injuries towards full restoration of tissue structure and subsequent function. Numerous studies have demonstrated that mobilization of endogenous stem cells or exogenous administration of a number of stem cell populations to injured tissues has resulted in structural regeneration of tissue as well as functional improvement. While the original hypothesis underlying stem cell regenerative therapies was based on functional recovery as a consequence of stem cell differentiation, it is now clear that other mechanisms of action are at play. A recent paradigm shift has emerged suggesting that the biomolecules synthesized by stem cells may be as important, if not more so, than differentiation of the cells in eliciting functional tissue repair. The fate of a stem cell is determined by its niche, or local microenvironment, consisting of surrounding cells and the secreted products of the stem cell [1]. Stem cells actively contribute to their environment by secreting cytokines, growth factors and extracellular matrix (ECM) molecules that act either on themselves (autocrine actions) or