CXCR4-transduced mesenchymal stem cells protect mice against graft-versus-host disease

Chen, Wei; Li, Miao; Li, Zhenyu; Zhang, Yan; Cheng, Hai; Pan, Bin; Cao, Jiang; Chen, Chong; Zeng, Lingyu; Xu, Kailin

doi:10.1016/j.imlet.2012.01.015

Cited by 19 publications

(16 citation statements)

References 46 publications

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“…A possible explanation for this increased therapeutic effect in the GVHD model is that MenSCs migrate at a higher rate and display a better homing potency than BM‐MSCs in vivo. Our results, are in line with the study that has shown that mice treated with MSCs overexpressing the migration molecule CXCR4 significantly increased the survival of GVHD through an enhanced migration potential . Indeed, we demonstrated that the expression of CXCR4 was significantly higher in MenSCs than BM‐MSCs and this was correlated with a superior migration rate of MenSCs in vitro.…”

Section: Discussionsupporting

confidence: 92%

“…For that purpose, we assessed the migratory capacity of both BM‐MSCs and MenSCs since the ability of MSC to migrate into the damage tissue is one of the main mechanisms that contribute to tissue regeneration . Since MSCs overexpressing the migratory molecule CXCR4 displayed a significantly increased migratory capacity in vitro together with a decreased mortality rate in a GVHD model we decided to study the expression level of CXCR4 in BM‐MSCs and MenSCs. Our results showed that a higher percentage of CXCR4 + cells was found in the MenSC population compared to BM‐MSCs (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…At 8 days postinjection, MenSCs were able to efficiently home into the intestine, spleen, and liver and in a higher rate than BM‐MSCs. Importance of MSC migration and homing has been detailed in some studies and shown to improve animal survival in GVHD where inefficient migration, survival, and homing limits the therapeutic effect of MSCs in GVHD . Moreover, all of these factors are important properties that can explain the outcome observed in the GVHD model.…”

Section: Discussionmentioning

confidence: 99%

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The immunosuppressive signature of menstrual blood mesenchymal stem cells entails opposite effects on experimental arthritis and graft versus host diseases

et al. 2015

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Recently, a noninvasive and highly proliferative stem cell population from menstrual blood called MenSCs has been identified. Despite their use in clinical studies, their immunomodulatory properties have not yet been investigated. In this context, we studied the immunosuppressive properties of MenSCs in comparison with the well-characterized bone marrow derived-MSCs (BM-MSCs). Using an in vitro proliferation assays, we showed that MenSCs displayed a lower suppressive effect on peripheral blood mononuclear cells and in particular on the proinflammatory CD4 1 IFN-c1 and CD81 IFNc 1 cells than BM-MSCs. Moreover, compared to BM-MSCs, MenSCs activated with IFN-c and IL-1b produced lower amounts of immunosuppressive factors such as IDO, PDL-1, PGE2, and Activin A and exhibited a substantial lower expression level of IFN-c receptor subunits. In the collagen induced arthritis model, while BM-MSCs administration resulted in a potent therapeutic effect associated with a significant decrease of proinflammatory T cell frequency in the lymph nodes, MenSCs injection did not. In contrast, in the xeno-GVHD model, only MenSCs administration significantly increased the survival of mice. This beneficial effect mediated by MenSCs was associated with a higher capacity to migrate into the intestine and liver and not to their anti-inflammatory capacities. All together our results demonstrate for the first time that the therapeutic potential of MSC in the experimental xeno-GVHD model is independent of their immunosuppressive properties. These findings should be taken into consideration for the development of safe and effective cell therapies. STEM CELLS 2016;34:456-469 SIGNIFICANCE STATEMENTIn the present study we report for the first time the immunosuppressive properties of MenSCs. We showed that they present lower immunosupressive properties compared to bone marrowMSCs, evidenced by lower expression of several immunomodulatory factors, and the absence of beneficial effect in experimental arthritis model. However, their therapeutic effect was maintained in the xeno-GVHD model, but this was independent on their antiinflammatory capacities. Since the use of MenSC has being proposed for several clinical trials the information provided here raises the alertness for evaluating carefully their potential side effects, a key prerequisite for the development of safe cell therapies.

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Section: Discussionsupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The immunosuppressive signature of menstrual blood mesenchymal stem cells entails opposite effects on experimental arthritis and graft versus host diseases

et al. 2015

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“…Eight-to10-week-old male C57BL/6 (H-2b) and female BALB/c (H-2d) mice were purchased from the Chinese Academy of Medical Sciences (Beijing, China) and the Third Military Medical University (Chongqin, China), respectively. We made slight modifications to the protocols for induction of aGVHD reported elsewhere (22)(23)(24).…”

Section: Experimental Animalsmentioning

confidence: 99%

High expression of heme oxygenase-1 in target organs may attenuate acute graft-versus-host disease through regulation of immune balance of TH17/Treg

Wang

Fang

et al. 2016

Transplant Immunology

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The high incidence of acute graft-versus-host disease (aGVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Grades III and IV aGVHD are the leading causes of death in allo-HSCT recipients. Heme oxygenase-1(HO-1) has anti-inflammatory and immune-regulatory functions. In this study, we evaluated the none GVHD and grade I-IV patients samples which were collected at the first re-examination after successful allo-HSCT, we found that expressions of HO-1 mRNA in the bone marrow and peripheral blood mononuclear cells of allo-HSCT recipients who had subsequent non-GVHD and grade I aGVHD were significantly higher than those in patients with Grade III-IV aGVHD. We then demonstrated that enhanced expression of HO-1 in target organs by infusing HO-1-gene-modified Mesenchymal stem cells (MSCs) alleviated the clinical and histopathological severity of aGVHD in experimental mice. Flow cytometry revealed a higher expression of Treg cells and a lower expression of TH17 cells in splenic and lymph node tissues of mice with enhanced HO-1 expression, as compared to that in the aGVHD mice. This was further substantiated by lower expression levels of ROR-Υt and IL-17A mRNA, and higher levels of Foxp3 mRNA in the splenic tissue of mice with enhanced HO-1 expression. Our results indicate that high expression of HO-1 may reduce the severity of aGVHD by regulation of the TH17/Treg balance.

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“…Wharton's jelly-derived mesenchymal stem cells (WJMSCs) can differentiate into cartilage cells, hair follicle epithelial cells, liver cells, female reproductive cells or neural cells under specified conditions, showing multidirectional differentiation potential and acting as seed cells for cell replacement therapy (Buhi, 2002;Breymann et al, 2006;Chang et al, 2011;Chen et al, 2012). They do not express Main histocompatibility complex (MHC) II and have low immunogenicity and low or no expression of MHCI (Gnoth et al, 2005;Cohen and Prince, 2013); hence, they have been widely used in fields such as genetics, immunology, and tissue repair and are the hot topic in stem cell research.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic influence of intraperitoneal injection of Wharton's jelly-derived mesenchymal stem cells on oviduct function and fertility in rats with acute and chronic salpingitis

et al. 2015

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ABSTRACT.To study the effect of Wharton's jelly-derived mesenchymal stem cells (WJMSCs) on the rat salpingitis model, 50 female Wistar rats were randomly divided into one control and five model groups. Mixed bacteria were injected into the oviducts of model groups. The treated acute and chronic groups received intraperitoneal injections of WJMSCs (1 x 10 6 ) once a week for three weeks. Serum inflammation factor, collagen fiber content and oviduct-specific glycoprotein (OVGP) levels were detected in control, chronic, ex-treatment acute and chronic, and treated acute and chronic groups (N = 5 for each group). Pregnancy rate and litter size of control, chronic, treated acute and treated chronic groups were compared. Serum TNF-α and INF-γ levels increased in ex-treatment acute and chronic groups, and restored to normal in the acute treated group but not in the treated chronic group. Oviduct collagen fibers did not increase significantly before or after treatment in the acute group, but it increased in the ex-treatment chronic group and did not improve after treatment. After treatment, OVGP levels restored to normal in the acute group but reduced in the ex-treatment and treated chronic groups and chronic group. The pregnancy rate and litter size of the treated acute group recovered to normal, but in the treated chronic group and chronic model group, they decreased significantly. Thus, intraperitoneal injection of WJMSCs could recover the function of the oviduct in acute salpingitis rats, but its effect on chronic salpingitis was poor. Timely treatment of salpingitis is crucial to preserve reproductive function.

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CXCR4-transduced mesenchymal stem cells protect mice against graft-versus-host disease

Cited by 19 publications

References 46 publications

The immunosuppressive signature of menstrual blood mesenchymal stem cells entails opposite effects on experimental arthritis and graft versus host diseases

The immunosuppressive signature of menstrual blood mesenchymal stem cells entails opposite effects on experimental arthritis and graft versus host diseases

High expression of heme oxygenase-1 in target organs may attenuate acute graft-versus-host disease through regulation of immune balance of TH17/Treg

Therapeutic influence of intraperitoneal injection of Wharton's jelly-derived mesenchymal stem cells on oviduct function and fertility in rats with acute and chronic salpingitis

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