Extrinsic and Intrinsic Mechanisms by Which Mesenchymal Stem Cells Suppress the Immune System

Coulson‐Thomas, Vivien Jane; Coulson-Thomas, Yvette M.; Gesteira, Tarsis F.; Kao, Winston W.‐Y.

doi:10.1016/j.jtos.2015.11.004

Cited by 64 publications

(55 citation statements)

References 195 publications

(145 reference statements)

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“…Subsequently, multi investigation have been explored an alternative strategy to produce MSCs. It's reported that secretion of growth factors, miRNAs, and EVs effects on the biological properties of stem cells including stem cell regeneration, differentiation potential, and immunomodulatory roles . Interestingly, the regulatory factors secreted from condition medium of MSCs improved the kidney and myocardial damages in animal model .…”

Section: Mscs Release Extracellular Vesicles As a Novel Approach Of Cmentioning

confidence: 99%

“…It's reported that secretion of growth factors, miRNAs, and EVs effects on the biological properties of stem cells including stem cell regeneration, differentiation potential, and immunomodulatory roles. 125 Interestingly, the regulatory factors secreted from condition medium of MSCs improved the kidney and myocardial damages in animal model. 126 Last several decades, MSCs immunoregulatory effects such as suppression of T and B cells proliferation, inducing tolerant dendritic cells (DCs), anti-inflamatory cytokines secretion have been demonstrated.…”

Section: Ev Components and Biological Functionsmentioning

confidence: 99%

See 1 more Smart Citation

The extracellular vesicles‐derived from mesenchymal stromal cells: A new therapeutic option in regenerative medicine

Nooshabadi¹,

Mardpour²,

Yousefi‐Ahmadipour³

et al. 2018

J of Cellular Biochemistry

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Mesenchymal stem cells (MSCs) are adult multipotent cells that due to their ability to homing to damaged tissues and differentiate into specialized cells, are remarkable cells in the field of regenerative medicine. It's suggested that the predominant mechanism of MSCs in tissue repair might be related to their paracrine activity. The utilization of MSCs for tissue repair is initially based on the differentiation ability of these cells; however now it has been revealed that only a small fraction of the transplanted MSCs actually fuse and survive in host tissues. Indeed, MSCs supply the microenvironment with the secretion of soluble trophic factors, survival signals and the release of extracellular vesicles (EVs) such as exosome. Also, the paracrine activity of EVs could mediate the cellular communication to induce cell-differentiation/self-renewal. Recent findings suggest that EVs released by MSCs may also be critical in the physiological function of these cells. This review provides an overview of MSC-derived extracellular vesicles as a hopeful opportunity to advance novel cell-free therapy strategies that might prevail over the obstacles and risks associated with the use of native or engineered stem cells. EVs are very stable; they can pass the biological barriers without rejection and can shuttle bioactive molecules from one cell to another, causing the exchange of genetic information and reprogramming of the recipient cells. Moreover, extracellular vesicles may provide therapeutic cargo for a wide range of diseases and cancer therapy.

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Section: Mscs Release Extracellular Vesicles As a Novel Approach Of Cmentioning

confidence: 99%

Section: Ev Components and Biological Functionsmentioning

confidence: 99%

The extracellular vesicles‐derived from mesenchymal stromal cells: A new therapeutic option in regenerative medicine

Nooshabadi¹,

Mardpour²,

Yousefi‐Ahmadipour³

et al. 2018

J of Cellular Biochemistry

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“…However, the molecular and cellular mechanisms of UMSCs that modulate inflammation and host immune response remain elusive. 5, 6 We previously showed that human UMSCs survived xenograft transplantation, caused low inflammatory responses and successfully corrected corneal clouding defects associated with congenital lysosomal storage disease MPS VII ( Gusb ) and in Lum −/− mice. 25, 27, 30 However, the precise mechanism by which UMSCs suppress the immune system remains elusive.…”

Section: Use Of Umsc and Bmsc For Treating Congenital Corneal Diseases‡mentioning

confidence: 99%

Cell Therapy of Corneal Diseases

Kao

Coulson‐Thomas²

2016

Cornea

Self Cite

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Mesenchymal stem cells (MSC) isolated from connective tissues are pluripotent and differentiate to phenotypes of connective tissue cell lineages (osteoblasts, chondrocytes, adipocytes) in vitro and in vivo. They have been used to treat mouse models of connective tissue disease such as Lumican null (Lum−/−), and mucopolysaccharidosis (Gusb) mice. MSC have unique immunosuppressive properties allowing evasion of host rejection; thus, they are valuable tools for cell therapy of congenital and acquired diseases involving immune dysfunction of multiple tissues including ocular surface tissues (cornea). We previously showed that human umbilical mesenchymal stem cells (UMSCs) modulated host immune responses, enabling them to survive xenograft transplantations. In vitro UMSCs modulated inflammatory cells by inhibiting adhesion and invasion, and inducing cell death. UMSC also regulated M1/M2 macrophage polarization and induced T-regulatory cell maturation from naïve intraperitoneal cavity lavage cells. UMSCs exposed to inflammatory cells synthesized a rich extracellular glycocalyx composed of hyaluronan (HA) bound to the heavy chains (HCs) of inter-alpha-trypsin inhibitor (HC-HA), which contains tumor necrosis factorα-stimulated gene 6 (TSG6) that catalyzes the transfer of HCs to HA, versican and pentraxin-3. Our in vivo and in vitro results showed that glycocalyx regulated inflammatory cells, allowing UMSCs to survive host immune rejection. Administration of antibodies against glycocalyx constituents or digestion with hyaluronidase and chondroitinase ABC abolished the UMSC ability to modulate immune responses. Treatment with anti-CD44 antibodies also diminished modulation of M2 macrophages by UMSC, indicating cell surface CD44 is required for correct UMSC glycocalyx assembly to modulate inflammatory cells.

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“…Sophisticated gene expression analysis can detect molecular differences, however these are lost upon culturing in vitro [22,23]. MSCs primarily have immunosuppressive roles while fibroblasts can show both pro- and anti-inflammatory roles [24-26]. As MSCs, fibroblasts and myofibroblasts may represent different states of differentiation, other immune cell inputs may play the deciding role in determining the maturation of MSCs and fibrotic potential.…”

Section: Cellular Response To Injury and Cross-regulating Cell-to-mentioning

confidence: 99%

Chasing the recipe for a pro-regenerative immune system

Godwin

Pinto

Rosenthal

2017

Seminars in Cell & Developmental Biology

103

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Identification of the key ingredients and essential processes required to achieve perfect tissue regeneration in humans has so far remained elusive. Injury in vertebrates induces an obligatory wound response that will precede or overlap any regeneration specific program or scarring outcome. This process shapes the cellular and molecular landscape of the tissue, influencing the success of endogenous repair pathways or for potential clinical intervention. The involvement of immune cells is also required for aspects of development extending beyond the initial inflammatory phase of wounding. It has now become clear from amphibian, fish and mammalian models of tissue injury that the type of immune response and the profile of immune cells attending the site of injury can act as the gatekeepers that determine wound repair quality. The heterogeneity among innate and adaptive immune cell populations, along with the developmental origin of these cells, form key ingredients affecting the potential for downstream repair and the suppression of fibrosis. Cell-to-cell interactions between immune cells, such as macrophages and T cells, with stem cells and mesenchymal cells are critically important for shaping this process and these exchanges, are in turn influenced by the type of injury, tissue location and developmental stage of the organism. Developmentally, mouse cardiac regeneration is restricted to early stages of postnatal life where the balance of innate to adaptive immune cells may be poised towards regeneration. In the injured adult mouse liver, specific macrophage subsets improve repair while other bone marrow derived cells can exacerbate injury. Other studies using genetically diverse mice have shown enhanced regeneration in certain strains, restricted to specific tissues. This enhanced repair is linked with expression of genes such as Insulin-like Growth Factor- 1 (IGF-1) and activin (Act 1), that both play important roles in shaping the immune system. Immune cells are now appreciated to have powerful influences on critical cell types required for regeneration success. The winning recipe for tissue regeneration is likely to be found ultimately by identifying the genetic elements and specific cell populations that limit or allow intrinsic potential. This will be essential for developing therapeutic strategies for tissue regeneration in humans.

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Extrinsic and Intrinsic Mechanisms by Which Mesenchymal Stem Cells Suppress the Immune System

Cited by 64 publications

References 195 publications

The extracellular vesicles‐derived from mesenchymal stromal cells: A new therapeutic option in regenerative medicine

The extracellular vesicles‐derived from mesenchymal stromal cells: A new therapeutic option in regenerative medicine

Cell Therapy of Corneal Diseases

Chasing the recipe for a pro-regenerative immune system

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