Co-infusion of donor bone marrow with host mesenchymal stem cells treats GVHD and promotes vascularized skin allograft survival in rats

Aksu, Ali̇ Emre; Horibe, Elaine K.; Sacks, Justin M.; Ikeguchi, Ryosuke; Breitinger, Jeremy; Scozio, Merissa; Unadkat, Jashvant D.; Feili-Hariri, Maryam

doi:10.1016/j.clim.2008.02.003

Cited by 85 publications

(70 citation statements)

References 51 publications

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“…Transplantation of allogeneic bone marrow-derived flk-1+Sca-1-MSCs led to stable mixed hematopoietic chimerism, permanent donor-specific immunotolerance in allogeneic host and long-term allogeneic skin graft acceptance [34] . The co-infusion of MSCs with unmodified donor bone marrow limited the toxicity of allogeneic bone marrow transplantation, treated graft vs host disease (GVHD), enhanced mixed chimerism and improved vascularized skin graft survival [35] . The high level of TNF-α also demonstrated a possible immunogenic role for donor (allogeneic) MSCs against skin allograft rejection [36] .…”

Section: Necrosismentioning

confidence: 99%

New advances in the mesenchymal stem cells therapy against skin flaps necrosis

Zhang¹

2014

WJSC

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Mesenchymal stem cells (MSCs), multipotential cells that reside within the bone marrow, can be induced to differentiate into various cells, such as osteoblasts, adipocytes, chondrocytes, vascular endothelial progenitor cells, and other cell types. MSCs are being widely studied as potential cell therapy agents due to their angiogenic properties, which have been well established by in vitro and in vivo researches. Within this context, MSCs therapy appears to hold substantial promise, particularly in the treatment of conditions involving skin grafts, pedicle flaps, as well as free flaps described in literatures. The purpose of this review is to report the new advances and mechanisms underlying MSCs therapy against skin flaps necrosis.

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Section: Necrosismentioning

confidence: 99%

New advances in the mesenchymal stem cells therapy against skin flaps necrosis

Zhang¹

2014

WJSC

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“…[16][17][18] Rehman et al 16 reported that the secretion of VEGF increases in hypoxia, and that ischemic hindlimbs were improved by MSC therapy. Boumaza et al 18 reported that MSCs spontaneously secrete HGF and TGFb1 and establish a tissue microenvironment that supports b cells.…”

mentioning

confidence: 99%

A Method for Performing Islet Transplantation Using Tissue-Engineered Sheets of Islets and Mesenchymal Stem Cells

Hirabaru

Kuroki

Adachi

et al. 2015

Tissue Engineering Part C: Methods

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Mesenchymal stem cells (MSCs) are known to have a protective effect on islet cells. Cell sheets developed using tissue engineering help maintain the function of the cells themselves. This study describes a tissue engineering approach using islets with MSC sheets to improve the therapeutic effect of islet transplantation. MSCs were obtained from Fischer 344 rats and engineered into cell sheets using temperature-responsive culture dishes. The islets obtained from Fischer 344 rats were seeded onto MSC sheets, and the islets with MSC sheets were harvested by low-temperature treatment after coculture. The functional activity of the islets with MSC sheets was confirmed by a histological examination, insulin secretion assay, and quantification of the levels of cytokines. The therapeutic effects of the islets with MSC sheets were investigated by transplanting the sheets at subcutaneous sites in severe combined immunodeficiency (SCID) mice with streptozotocin-induced diabetes. Improvement of islet function and viability was shown in situ on the MSC sheet, and the histological examination showed that the MSC sheet maintained adhesion factor on the surface. In the recipient mice, normoglycemia was maintained for at least 84 days after transplantation, and neovascularization was observed. These results demonstrated that islet transplantation in a subcutaneous site would be possible by using the MSC sheet as a scaffold for islets.

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“…35,36 It has been reported that co-infusion of MSCs with unmodified bone marrow limits the toxicity of allogeneic bone marrow transplantation, enhances mixed chimerism and improves vascularized skin graft survival in rats. Secretion of high levels of IL-6, TGF-b1 and hepatocyte growth factor but not IL-10 or IL-4 by MSC could play a role in their anti-inflammatory and immunoregulatory function.…”

Section: Cd25mentioning

confidence: 99%

“…Secretion of high levels of IL-6, TGF-b1 and hepatocyte growth factor but not IL-10 or IL-4 by MSC could play a role in their anti-inflammatory and immunoregulatory function. 35 Considering that we prepared the stromal cells from spleen but not from bone marrow, MSCs derived from spleen stromal cells could also play a partial role in inhibiting allogeneic T-cell proliferation. Indeed, we observed that IL-10-producing regulatory DCs and/or T cells exhibited the ability to inhibit allogeneic T-cell proliferation and reduce IFN-c secretion, thereby downregulating alloreactive T-cell responses (Figure 8).…”

Section: Cd25mentioning

confidence: 99%

Indoleamine 2,3-dioxygenase and regulatory dendritic cells contribute to the allograft protection induced by infusion of donor-specific splenic stromal cells

et al. 2010

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It has been reported that splenic stromal cells (SSCs) are capable of directly supporting the development of CD11c lo CD45RB 1 IL-10-producing dendritic cells (DCs) from lineage-negative c-kit 1 progenitor cells in the absence of exogenous cytokines. In vitro, DCs that differentiate on stromal cells suppress mixed leukocyte reaction responses and induce primary alloreactive CD41 T cells to differentiate into IL-10-producing Tr1 cells. However, the precise mechanisms by which these SSCs exert their regulatory functions in vivo remain undefined. Furthermore, their possible contribution to the development of allograft transplantation tolerance has yet to be examined. Here, we have used both murine skin and cardiac allograft transplantation models to explore whether in vivo alloresponses can be regulated by infusion with donor-derived SSCs and to investigate the possible mechanisms by which SSCs exert regulatory effects to prevent allograft rejection. We show that intravenous SSC infusion prolonged murine skin allograft survival. The prolonged graft survival is associated with augmentation of the generation of regulatory DC subsets and CD4 Foxp31 regulatory T cells (Tregs), as well as upregulation of the production of suppressive cytokines IL-10 and transforming growth factor (TGF)-b. Moreover, we found that indoleamine 2,3-dioxygenase and SSC-derived regulatory DCs contribute to allograft protection by infusion of donor-specific SSCs. Our data suggest that donor-derived SSCs could be used as a therapeutic target to promote transplantation tolerance.

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Co-infusion of donor bone marrow with host mesenchymal stem cells treats GVHD and promotes vascularized skin allograft survival in rats

Cited by 85 publications

References 51 publications

New advances in the mesenchymal stem cells therapy against skin flaps necrosis

New advances in the mesenchymal stem cells therapy against skin flaps necrosis

A Method for Performing Islet Transplantation Using Tissue-Engineered Sheets of Islets and Mesenchymal Stem Cells

Indoleamine 2,3-dioxygenase and regulatory dendritic cells contribute to the allograft protection induced by infusion of donor-specific splenic stromal cells

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