Mesenchymal Stem Cells Prolong Composite Tissue Allotransplant Survival in a Swine Model

Kuo, Yur‐Ren; Goto, Shigeru; Shih, Hsiang Shun; Wang, Feng Sheng; Lin, Chien Chih; Wang, Chun Ting; Huang, Eagle Yi‐Kung; Chen, Chao Long; Wei, Fu; Zheng, Xin Xiao; Lee, W. P.Andrew

doi:10.1097/tp.0b013e3181a664f1

Cited by 82 publications

(79 citation statements)

References 31 publications

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“…Bone marrow stromal cells (BMSCs) have recently been shown to suppress harmful immune responses in patients with acute graftversus-host disease (4,5) and in several animal models of allogeneic rejection (6)(7)(8), a variety of autoimmune diseases (9)(10)(11), and lung injury (12)(13)(14)(15). The authors of many of these studies concluded that BMSC-driven immunosuppression results from a shift in Th1/Th2 balance (8,16,17).…”

mentioning

confidence: 99%

Bone marrow stromal cells use TGF-β to suppress allergic responses in a mouse model of ragweed-induced asthma

Nemeth

Keane‐Myers

Brown

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

388

350

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Bone marrow stromal cells [BMSCs; also known as mesenchymal stem cells (MSCs)] effectively suppress inflammatory responses in acute graft-versus-host disease in humans and in a number of disease models in mice. Many of the studies concluded that BMSC-driven immunomodulation is mediated by the suppression of proinflammatory Th1 responses while rebalancing the Th1/Th2 ratio toward Th2. In this study, using a ragweed induced mouse asthma model, we studied if BMSCs could be beneficial in an allergic, Th2-dominant environment. When BMSCs were injected i.v. at the time of the antigen challenge, they protected the animals from the majority of asthma-specific pathological changes, including inhibition of eosinophil infiltration and excess mucus production in the lung, decreased levels of Th2 cytokines (IL-4, IL-5, and IL-13) in bronchial lavage, and lowered serum levels of Th2 immunoglobulins (IgG1 and IgE). To explore the mechanism of the effect we used BMSCs isolated from a variety of knockout mice, performed in vivo blocking of cytokines and studied the effect of asthmatic serum and bronchoalveolar lavage from ragweed challenged animals on the BMSCs in vitro. Our results suggest that IL-4 and/or IL-13 activate the STAT6 pathway in the BMSCs resulting in an increase of their TGF-β production, which seems to mediate the beneficial effect, either alone, or together with regulatory T cells, some of which might be recruited by the BMSCs. These data suggest that, in addition to focusing on graft-versus-host disease and autoimmune diseases, allergic conditions—specifically therapy resistant asthma—might also be a likely target of the recently discovered cellular therapy approach using BMSCs.

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mentioning

confidence: 99%

Bone marrow stromal cells use TGF-β to suppress allergic responses in a mouse model of ragweed-induced asthma

Nemeth

Keane‐Myers

Brown

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

388

350

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“…Based on previous observations, we speculated that BMSCs might represent a useful cell in clinical practices (Hu et al, 2010;Griffin et al, 2011;Gurudutta et al, 2012). Indeed, the advantage of employing large animals, such as pigs, rather than small animal models, is based on several factors, including disease complexity, effective cell dosage, cell survival after transplantation, as well as tissue related inflammatory and immunological responses to engraftment after transplantation (Poncelet et al, 2007;Kuo et al, 2009). Xiaomeishan porcine BMSCs were chosen for this study based on their similarity to human cells.…”

Section: Discussionmentioning

confidence: 99%

Oct4 and Sox2 overexpression improves the proliferation and differentiation of bone mesenchymal stem cells in Xiaomeishan porcine

Fan¹,

Gu²,

Zhang³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Mesenchymal stem cells derived from bone marrow (BMSCs) are a population of self-renewing multipotent cells that are capable of differentiating into various cellular lineages, and are widely employed in tissue engineering and cell therapy. Recently, clinical research involving BMSCs has become increasingly popular. In order to conduct appropriate research, it is first necessary to amplify large amounts of functional BMSCs in vitro. However, after several passages of expanding in vitro, the proliferation and differentiation potential of BMSCs gradually decline. To determine whether overexpression of Oct4 or Sox2 might prevent this decline, we transfected Oct4 or Sox2, which are essential for the pluripotency and self-renewal of embryonic stem cells, into BMSCs of Xiaomeishan porcine by a lentivirus. The results showed that overexpression of Sox2 or Oct4 BMSCs in culture media containing a basic fibroblast growth factor resulted in higher proliferation and differentiation compared to controls, suggesting that genetic modification of stemness-related genes is an efficient way to maintain the proliferation and differentiation potential of BMSCs.

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“…Among many available sources, mesenchymal stem cells (MSCs) derived from bone marrow or adipose tissue are commonly used as multipotent autologous cell sources and can be collected through relatively noninvasive methods. 1 A number of studies have demonstrated the advantages of using MSCs for the repair or regeneration of multiple tissue types, [2][3][4][5][6][7][8][9] and multiple clinical trials are underway investigating the use of MSCs for the treatment of both acute and chronic conditions. 10 Despite many studies establishing the benefits of MSCs, a number of factors remain unaddressed regarding their widespread use.…”

Section: Introductionmentioning

confidence: 99%

Uncultured Marrow Mononuclear Cells Delivered Within Fibrin Glue Hydrogels to Porous Scaffolds Enhance Bone Regeneration Within Critical-Sized Rat Cranial Defects

Kretlow

Spicer

Jansen

et al. 2010

Tissue Engineering Part A

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For bone tissue engineering, the benefits of incorporating mesenchymal stem cells (MSCs) into porous scaffolds are well established. There is, however, little consensus on the effects of or need for MSC handling ex vivo. Culture and expansion of MSCs adds length and cost, and likely increases risk associated with treatment. We evaluated the effect of using uncultured bone marrow mononuclear cells (bmMNCs) encapsulated within fibrin glue hydrogels and seeded into porous scaffolds to regenerate bone over 12 weeks in an 8-mm-diameter, criticalsized rat cranial defect. A full factorial experimental design was used to evaluate bone formation within model poly(L-lactic acid) and corraline hydroxyapatite scaffolds with or without platelet-rich plasma (PRP) and bmMNCs. Mechanical push-out testing, microcomputed tomographical analyses, and histology were performed. PRP showed no benefit for bone formation. Cell-laden poly(L-lactic acid) scaffolds without PRP required significantly greater force to displace from surrounding tissues than control (cell-free) scaffolds, but no differences were observed during push-out testing of coral scaffolds. For bone volume formation as analyzed by microcomputed tomography, significant positive overall effects were observed with bmMNC incorporation. These data suggest that bmMNCs may provide therapeutic advantages in bone tissue engineering applications without the need for culture, expansion, and purification.

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Mesenchymal Stem Cells Prolong Composite Tissue Allotransplant Survival in a Swine Model

Abstract: These results suggested that the regulatory activity of MSCs on T cells and GVHD might contribute to significant prolongation of composite tissue allotransplant survival in the MSC-BMT-CsA treatment.

Cited by 82 publications

References 31 publications

Bone marrow stromal cells use TGF-β to suppress allergic responses in a mouse model of ragweed-induced asthma

Bone marrow stromal cells use TGF-β to suppress allergic responses in a mouse model of ragweed-induced asthma

Oct4 and Sox2 overexpression improves the proliferation and differentiation of bone mesenchymal stem cells in Xiaomeishan porcine

Uncultured Marrow Mononuclear Cells Delivered Within Fibrin Glue Hydrogels to Porous Scaffolds Enhance Bone Regeneration Within Critical-Sized Rat Cranial Defects

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