Multipotent mesenchymal stromal cells and the innate immune system

Mesenchymal stromal cells (MSCs) have immunomodulatory effects and are increasingly being used for the treatment of acute and chronic GVHD. Although they seem immuno-privileged, they induce alloresponses, but the risk of immunization is poorly characterized. After infusion, they first reach the lungs, liver and spleen, and are then difficult to trace. Several mechanisms are involved in stromal cells suppressing alloreactivity, such as induction of regulatory T cells, but whether or not this will also affect leukemic relapse or increase infections is not known. Although several encouraging pilot studies have been published, there have been few prospective randomized trials. There may be a bias in the literature, as negative results are seldom published, and there have been few comparative studies with other immunosuppressive regimens. Most animal models have failed to show any effect on GVHD. Several questions remain to be answered for optimization of stromal cell therapy. Which source is optimal-BM, fat, cord or decidua? Can stromal cells be replaced by exosomes, which culture conditions are most appropriate and at what passage and how frequently should cells be administered? More research is required to move stromal cell therapy forward to become an established treatment for acute and chronic GVHD.

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“…[41][42][43][44][45] In this section, we will briefly discuss some of these properties, which are summarized in Table 2.…”

Section: Immune Modulation By Mscsmentioning

confidence: 99%

Stromal cells–are they really useful for GVHD?

Kaipe

Erkers

Sadeghi

et al. 2014

Bone Marrow Transplant

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“…In contrast, MSCs can promote the differentiation to M2 macrophages which abundantly produce IL-10 [13]. These modulations of immune cells are associated with many soluble factors released from MSCs, including transforming growth factor-β1, hepatocyte growth factor, IL-10, indoleamine 2, 3-dioxygenase, prostaglandin E2, nitric oxide, matrix metalloproteinases, HLA-G (Figure 1) [11][12][13][14]. The secretion of these factors from MSCs has been shown to be induced by IFN-γ alone, or in combination with tumor necrosis factor (TNF)-α, IL-1α, or IL-1β [23].…”

Section: Immunomodulatory Function Of Mscsmentioning

confidence: 97%

“…The immunomodulatory effect of MSCs was first indicated by long term engraftment in a xenogeneic environment in 2000 [10]. Although its mechanisms have not been fully understood, previous studies have revealed that MSCs inhibited the function of immune cells via cell to cell contact dependent mechanism and several soluble immune modulators [11][12][13][14].…”

Section: Immunomodulatory Function Of Mscsmentioning

confidence: 99%

“…The differentiation from monocytes or hematopoietic cells to dendritic cells (DCs) and the maturation of DCs can be impaired by MSCs [22]. In contrast, MSCs can promote the differentiation to M2 macrophages which abundantly produce IL-10 [13]. These modulations of immune cells are associated with many soluble factors released from MSCs, including transforming growth factor-β1, hepatocyte growth factor, IL-10, indoleamine 2, 3-dioxygenase, prostaglandin E2, nitric oxide, matrix metalloproteinases, HLA-G (Figure 1) [11][12][13][14].…”

Section: Immunomodulatory Function Of Mscsmentioning

confidence: 99%

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Human Mesenchymal Stem Cell Therapy for Acute Graft Versus Host Disease

Yoshioka¹,

Miura²

2016

Transl Med

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Acute graft versus host disease (GVHD) is the most critical complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The understanding of major histocompatibility complex (MHC) and the development of acute GVHD prophylaxis have contributed to decreasing the incidence of severe acute GVHD. However, these progresses expand the chance of receiving allo-HSCT from human leukocyte antigen (HLA) mismatched donor. In addition, the expanding of indication for allo-HSCT to elderly patients or patients with organ dysfunction by the pervasiveness of reduced-intensity conditioning is associated with increased risk of acute GVHD. Unexpectedly, severe refractory acute GVHD can occur even in allo-HSCT from HLA matched sibling donor. The first line therapy for severe acute GVHD is corticosteroid, but the second line therapy has not been established and the prognosis of steroid-resistant acute GVHD remains poor. Recently, the efficacy of human bone marrow mesenchymal stem cell (MSC) therapy for steroid-resistant acute GVHD has been consistently reported. MSCs are approved as a cell therapy drug for steroid-resistant acute GVHD in some countries. We here review the history and the future of MSC therapy for acute GVHD.

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“…Studies have demonstrated that MSCs are immunomodulatory and are capable of reducing pathogenic inflammation [31]. MSCs can exert profound immunosuppression both in vitro and in vivo by inhibiting the proliferation of T-cells, natural killer cells, and dendritic cells [32].…”

Section: Phenotype Of Mscsmentioning

confidence: 99%

Mesenchymal stem cell-based therapy for ischemic stroke

et al. 2016

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Ischemic stroke represents a major, worldwide health burden with increasing incidence. Patients affected by ischemic strokes currently have few clinically approved treatment options available. Most currently approved treatments for ischemic stroke have narrow therapeutic windows, severely limiting the number of patients able to be treated. Mesenchymal stem cells represent a promising novel treatment for ischemic stroke. Numerous studies have demonstrated that mesenchymal stem cells functionally improve outcomes in rodent models of ischemic stroke. Recent studies have also shown that exosomes secreted by mesenchymal stem cells mediate much of this effect. In the present review, we summarize the current literature on the use of mesenchymal stem cells to treat ischemic stroke. Further studies investigating the mechanisms underlying mesenchymal stem cells tissue healing effects are warranted and would be of benefit to the field.

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Multipotent mesenchymal stromal cells and the innate immune system

Cited by 863 publications

References 137 publications

Stromal cells–are they really useful for GVHD?

Stromal cells–are they really useful for GVHD?

Human Mesenchymal Stem Cell Therapy for Acute Graft Versus Host Disease

Mesenchymal stem cell-based therapy for ischemic stroke

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