Potential application of mesenchymal stem cells in acute lung injury

Article (PDF Available)inExpert opinion on biological therapy 9(10):1259-70 · September 2009with34 Reads
DOI: 10.1517/14712590903213651 · Source: PubMed
Despite extensive research into the pathogenesis of acute lung injury and the acute respiratory distress syndrome (ALI/ARDS), mortality remains high at approximately 40%. Current treatment is primarily supportive, with lung-protective ventilation and a fluid conservative strategy. Pharmacologic therapies that reduce the severity of lung injury in experimental studies have not yet been translated into effective clinical treatment options. Therefore, innovative therapies are needed. Recent studies have suggested that bone-marrow-derived multipotent mesenchymal stem cells (MSC) may have therapeutic applications in multiple clinical disorders including myocardial infarction, diabetes, sepsis, hepatic and acute renal failure. Recently, MSC have been studied in several in vivo models of lung disease. This review focuses on first describing the existing experimental literature that has tested the use of MSC in models of ALI/ARDS, and then the potential mechanisms underlying their therapeutic use with an emphasis on secreted paracrine soluble factors. The review concludes with a discussion of future research directions required for potential clinical trials.


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Available from: Naveen Gupta, Jan 29, 2014
    • "MSCs release potent growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), hepatocyte growth factor (HGF), keratinocyte growth factor (KGF), monocyte chemoattractant protein-1 (MCP-1), SDF- 1, and fibroblast growth factor (FGF). These factors stimulate endogenous cellular repair mechanisms, including stimulation of proliferation and angiogenesis [93][94][95][96][97][98] . In response to inflammation , it has been demonstrated that MSCs modulate or alter inflammatory responses and release immune-mediators, such as IL-10, IL-6, TGF-b, prostaglandin E2 (PGE2), NO, and IDO and generate a local antiinflammatory proreparative cellular state [99, 100]. "
    [Show abstract] [Hide abstract] ABSTRACT: Advances in surgical techniques, immunology, and organ donor networking have allowed organ transplantation to evolve over the last several decades into a procedure that has saved hundreds of thousands of lives. While these dramatic advances have made organ transplantation more effective, they have also highlighted the growing shortage of donor organs. Unfortunately, many organs that could be of potential use for transplantation end up discarded due to short preservation times, often only 4–12 h for vital organs. Organ preservation systems have been investigated with renewed vigor in attempts to solve this problem, and new tools are becoming available that make solutions much more possible than ever before. The cryobiology of organs must be understood for long-term banking solutions to be feasible, combined with greater understanding of the physio-chemical processes that take place during ischemia and reperfusion. New approaches based on natural models, stem cells, and various novel proteins and trophic factors all show great promise in accomplishing the goal of more donor organs matched with more patients in need.
    Article · Apr 2016
    • "Moreover, MSCs also have therapeutic potential used in treating pulmonary fibrosis and acute renal nephropathy, and also in inhibiting the progress of diabetes. MSCs transplantation promotes the development and expansion of b cells and renal glomeruli as well as decreasing collagen declaration and inflammation in fibrosis (Lee et al. 2009, Vija et al. 2009) (Urban et al. 2008). Furthermore, MSCs infusion can be very useful in cord blood transplantation where the restricted amount of stem cells delays engraftment and favors graft rejection. "
    [Show abstract] [Hide abstract] ABSTRACT: Mesenchymal stem cells (MSCs) are a population of multipotent progenitors which reside in bone marrow, fat, and some other tissues and can be isolated from various adult and fetal tissues. Self-renewal potential and multipotency are MSC's hallmarks. They have the capacity of proliferation and differentiation into a variety of cell lineages like osteoblasts, condrocytes, adipocytes, fibroblasts, cardiomyocytes. MSCs can be identified by expression of some surface molecules like CD73, CD90, CD105, and lack of hematopoietic specific markers including CD34, CD45, and HLA-DR. They are hopeful tools for regenerative medicine for repairing injured tissues. Many studies have focused on two significant features of MSC therapy: (I) systemically administered MSCs home to sites of ischemia or injury, and (II) MSCs can modulate T-cell-mediated immunological responses. MSCs express chemokine receptors and ligands involved in cells migration and homing process. MSCs induce immunomedulatory effects on the innate (dendritic cells, monocyte, natural killer cells, and neutrophils) and the adaptive immune system cells (T helper-1, cytotoxic T lymphocyte, and B lymphocyte) by secreting soluble factors like TGF-β, IL-10, IDO, PGE-2, sHLA-G5, or by cell-cell interaction. In this review, we discuss the main applications of mesenchymal stem in Regenerative Medicine and known mechanisms of homing and Immunomodulation of MSCs.
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    • "These cells were first described as residing in the bone marrow (BM), which is currently the most extensively studied source for MSCs; however, MSCs have also been successfully isolated from tissues other than BM (e.g., umbilical cord blood [2], the placenta [3], amniotic fluid [4], adipose tissue [5], lung [6], skeletal muscle [7] and the dental pulp [8]). Due to their multipotential capacity [1] and immunomodulatory properties [9, 10], an increasing interest has emerged about the biological properties and the potential clinical application of these cells, as they may represent a potential source for cell-based therapy for tissue repair [11, 12] and for suppressing autoimmunity [13]. In addition, MSCs may also play an important role in the pathogenesis of several diseases, including hematological disorders such as multiple myeloma [14], chronic myeloid leukemia [15] and myelodysplastic syndromes [16, 17]. "
    [Show abstract] [Hide abstract] ABSTRACT: Introduction: Mesenchymal stem cells (MSCs) are multipotent cells capable of self-renewal and multilineage differentiation. Their multipotential capacity and immunomodulatory properties have led to an increasing interest in their biological properties and therapeutic applications. Currently, the definition of MSCs relies on a combination of phenotypic, morphological and functional characteristics which are typically evaluated upon in vitro expansion, a process that may ultimately lead to modulation of the immunophenotypic, functional and/or genetic features of these cells. Therefore, at present there is great interest in providing markers and phenotypes for direct in vivo and ex vivo identification and isolation of MSCs. Methods: Multiparameter flow cytometry immunophenotypic studies were performed on 65 bone marrow (BM) samples for characterization of CD13(high) CD105(+) CD45(-) cells. Isolation and expansion of these cells was performed in a subset of samples in parallel to the expansion of MSCs from mononuclear cells following currently established procedures. The protein expression profile of these cells was further assessed on (paired) primary and in vitro expanded BM MSCs, and their adipogenic, chondrogenic and osteogenic differentiation potential was also determined. Results: Our results show that the CD13(high) CD105(+) CD45(-) immunophenotype defines a minor subset of cells that are systematically present ex vivo in normal/reactive BM (n = 65) and that display immunophenotypic features, plastic adherence ability, and osteogenic, adipogenic and chondrogenic differentiation capacities fully compatible with those of MSCs. In addition, we also show that in vitro expansion of these cells modulates their immunophenotypic characteristics, including changes in the expression of markers currently used for the definition of MSCs, such as CD105, CD146 and HLA-DR. Conclusions: BM MSCs can be identified ex vivo in normal/reactive BM, based on a robust CD13(high) CD105(+) and CD45(-) immunophenotypic profile. Furthermore, in vitro expansion of these cells is associated with significant changes in the immunophenotypic profile of MSCs.
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