Stem cell paracrine actions and tissue regeneration
TL;DR: 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 are discussed.
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
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01 Jan 2011
TL;DR: The role of stem cells as restorative treatments for basal ganglia disorders, including Parkinson's disease, Huntington's disease and stroke, are discussed, with special emphasis to the recently investigated menstrual blood stem cells.
Abstract: 24 a b s t r a c t Cerebrovascular diseases are the third leading cause of death and the primary cause of long-term dis- ability in the United States. The only approved therapy for stroke is tPA, strongly limited by the short therapeutic window and hemorrhagic complications, therefore excluding most patients from its bene- fits. Parkinson's and Huntington's disease are the other two most studied basal ganglia diseases and, as stroke, have very limited treatment options. Inflammation is a key feature in central nervous system dis- orders and it plays a dual role, either improving injury in early phases or impairing neural survival at later stages. Stem cells can be opportunely used to modulate inflammation, abrogate cell death and, therefore, preserve neural function. We here discuss the role of stem cells as restorative treatments for basal gan- glia disorders, including Parkinson's disease, Huntington's disease and stroke, with special emphasis to the recently investigated menstrual blood stem cells. We highlight the availability, proliferative capacity, pluripotentiality and angiogenic features of these cells and explore their present and future experimental and clinical applications. © 2011 Published by Elsevier Ltd.
454 citations
TL;DR: This manuscript reviews the existent literature on how preconditioning of MSCs affects the therapeutic potential of their secretome, focusing on MSC's immunomodulatory and regenerative features, thereby providing new insights for the therapeutic use of M SCs' secretome.
Abstract: Mesenchymal stromal cells (MSCs) are self-renewing, culture-expandable adult stem cells that have been isolated from a variety of tissues, and possess multipotent differentiation capacity, immunomodulatory properties, and are relatively non-immunogenic. Due to this unique set of characteristics, these cells have attracted great interest in the field of regenerative medicine and have been shown to possess pronounced therapeutic potential in many different pathologies. MSCs' mode of action involves a strong paracrine component resulting from the high levels of bioactive molecules they secrete in response to the local microenvironment. For this reason, MSCs' secretome is currently being explored in several clinical contexts, either using MSC-conditioned media (CM) or purified MSC-derived extracellular vesicles (EVs) to modulate tissue response to a wide array of injuries. Rather than being a constant mixture of molecular factors, MSCs' secretome is known to be dependent on the diverse stimuli present in the microenvironment that MSCs encounter. As such, the composition of the MSCs' secretome can be modulated by preconditioning the MSCs during in vitro culture. This manuscript reviews the existent literature on how preconditioning of MSCs affects the therapeutic potential of their secretome, focusing on MSCs' immunomodulatory and regenerative features, thereby providing new insights for the therapeutic use of MSCs' secretome.
317 citations
Cites background from "Stem cell paracrine actions and tis..."
...Nevertheless, this paracrine action is known to be influenced by the microenvironment surrounding the cells (31)....
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TL;DR: The stem cell secretome (SCS) includes cytokines, chemokines and growth factors, and has gained increasing attention in recent years because of its multiple implications for the repair, restoration or regeneration of injured tissues.
285 citations
TL;DR: This review examines the three phases of morphological research that have occurred in the study of Sertoli cells, because microscopic anatomy was essentially the only scientific discipline available for about the first 75 years after the discovery of the testicular ‘nurse cell’.
Abstract: It has been one and a half centuries since Enrico Sertoli published the seminal discovery of the testicular 'nurse cell', not only a key cell in the testis, but indeed one of the most amazing cells in the vertebrate body. In this review, we begin by examining the three phases of morphological research that have occurred in the study of Sertoli cells, because microscopic anatomy was essentially the only scientific discipline available for about the first 75 years after the discovery. Biochemistry and molecular biology then changed all of biological sciences, including our understanding of the functions of Sertoli cells. Immunology and stem cell biology were not even topics of science in 1865, but they have now become major issues in our appreciation of Sertoli cell's role in spermatogenesis. We end with the universal importance and plasticity of function by comparing Sertoli cells in fish, amphibians, and mammals. In these various classes of vertebrates, Sertoli cells have quite different modes of proliferation and epithelial maintenance, cystic vs. tubular formation, yet accomplish essentially the same function but in strikingly different ways.
269 citations
Cites background from "Stem cell paracrine actions and tis..."
...Accumulating evidence suggests that stem cell self-renewal and differentiation depend on specialized microenvironments called niches (Spradling et al., 2001; Scadden, 2006) and that in turn stem cells influence their environment (Baraniak & McDevitt, 2010; Mosher et al., 2012; Sowa et al., 2012)....
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TL;DR: The development of a 3D culture system for mesenchymal stem cells that may circumvent limitations associated with conventional monolayer cultures and enhance the differentiation potential of multipotent cells is demonstrated.
Abstract: While traditional cell culture methods have relied on growing cells as monolayers, three-dimensional (3D) culture systems can provide a convenient in vitro model for the study of complex cell–cell and cell–matrix interactions in the absence of exogenous substrates and may benefit the development of regenerative medicine strategies. In this study, mesenchymal stem cell (MSC) spheroids, or “mesenspheres”, of different sizes, were formed using a forced aggregation technique and maintained in suspension culture for extended periods of time thereafter. Cell proliferation and differentiation potential within mesenspheres and dissociated cells retrieved from spheroids were compared to conventional adherent monolayer cultures. Mesenspheres maintained in growth medium exhibited no evidence of cell necrosis or differentiation, while mesenspheres in differentiation media exhibited differentiation similar to conventional 2D culture methods based on histological markers of osteogenic and adipogenic commitment. Furthermore, when plated onto tissue culture plates, cells that had been cultured within mesenspheres in growth medium recovered morphology typical of cells cultured continuously in adherent monolayers and retained their capacity for multi-lineage differentiation potential. In fact, more robust matrix mineralization and lipid vacuole content were evident in recovered MSCs when compared to monolayers, suggesting enhanced differentiation by cells cultured as 3D spheroids. Thus, this study demonstrates the development of a 3D culture system for mesenchymal stem cells that may circumvent limitations associated with conventional monolayer cultures and enhance the differentiation potential of multipotent cells.
237 citations
Cites background from "Stem cell paracrine actions and tis..."
...…potent trophic factors that contribute to tissue remodeling and are largely thought to be immunoprivileged cells, thereby providing for allogeneic, off-the-shelf administration of these cells or more differentiated progeny for regenerative medicine therapies (Baraniak and McDevitt 2010)....
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...of potent trophic factors that contribute to tissue remodeling and are largely thought to be immunoprivileged cells, thereby providing for allogeneic, off-the-shelf administration of these cells or more differentiated progeny for regenerative medicine therapies (Baraniak and McDevitt 2010)....
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References
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TL;DR: Insight is offered into the interactions between allogeneic MSCs and immune cells and mechanisms likely involved with the in vivo MSC-mediated induction of tolerance that could be therapeutic for reduction of GVHD, rejection, and modulation of inflammation.
4,264 citations
TL;DR: It is postulate that mesenchymal stem cells have a potent immunosuppressive effect in vivo and are transplanted in a patient with severe treatment-resistant grade IV acute graft-versus-host disease of the gut and liver.
2,636 citations
TL;DR: Infusion of mesenchymal stem cells expanded in vitro, irrespective of the donor, might be an effective therapy for patients with steroid-resistant, acute GVHD.
2,510 citations
TL;DR: Eight constructs decellularized hearts by coronary perfusion with detergents, preserved the underlying extracellular matrix, and produced an acellular, perfusable vascular architecture, competent a cellular valves and intact chamber geometry that could generate pump function in a modified working heart preparation.
Abstract: About 3,000 individuals in the United States are awaiting a donor heart; worldwide, 22 million individuals are living with heart failure. A bioartificial heart is a theoretical alternative to transplantation or mechanical left ventricular support. Generating a bioartificial heart requires engineering of cardiac architecture, appropriate cellular constituents and pump function. We decellularized hearts by coronary perfusion with detergents, preserved the underlying extracellular matrix, and produced an acellular, perfusable vascular architecture, competent acellular valves and intact chamber geometry. To mimic cardiac cell composition, we reseeded these constructs with cardiac or endothelial cells. To establish function, we maintained eight constructs for up to 28 d by coronary perfusion in a bioreactor that simulated cardiac physiology. By day 4, we observed macroscopic contractions. By day 8, under physiological load and electrical stimulation, constructs could generate pump function (equivalent to about 2% of adult or 25% of 16-week fetal heart function) in a modified working heart preparation.
2,454 citations
TL;DR: Baboon MSCs have been observed to alter lymphocyte reactivity to allogeneic target cells and tissues, which may prove useful in future applications of tissue regeneration and stem cell engineering.
2,273 citations