Stem Cell Paracrine Actions and Tissue Regeneration

Abstract

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

Anti-apoptotic Effects of Human Wharton's Jelly-derived Mesenchymal Stem Cells on Skeletal Muscle Cells Mediated via Secretion of XCL1

“…[30][31][32] Therefore, key secretory proteins of human MSCs are also used directly as novel treatments for patients and could be potent biomarkers for selection of superior human MSCs during large-scale cultivation of clinical grade human MSC in Good Manufacturing Practice facilities. 33 Based on these findings, we aimed to determine if either human MSCs or a selection of key secreted proteins may be applicable as novel treatments.…”

Plasma-functionalized electrospun matrix for biograft development and cardiac function stabilization

“…Up to now, a series of research work has demonstrated positive effects of cell therapy on reduction of cardiomyocyte necrosis, induction of angiogenesis and activation of host stem cell recruitment via the secretion of paracrine factors [43]. The clinical benefit of intramyocardial injection of autologous MSCs has also been increasingly reported [5].…”

Three-Dimensional In Vitro Tri-Culture Platform to Investigate Effects of Crosstalk Between Mesenchymal Stem Cells, Osteoblasts, and Adipocytes

“…3,4 To provide relevant platforms for evaluating regenerative medicine therapies, such in vitro systems should mimic niche environments of a three-dimensional (3D) tissue as closely as possible by allowing for dynamic cell-cell interactions, given that cellular responses can vary substantially depending on the surrounding microenvironment. 5,6 Toward this end, use of biomaterials may provide a way to recreate these 3D environments, while allowing the study of complex cellular interactions. This includes the application of methods for high-throughput, multivariate analyses of highcontent data (e.g., from gene microarrays, suspension arrays, time-of-flight-mass spectrometry, and microscopy images) [7][8][9][10][11] that yield system-level information of complex cellular processes at or close to a single-cell level.…”