Treatment with placenta-derived mesenchymal stem cells mitigates development of bronchiolitis obliterans in a murine model

Adesanya

et al. 2014

Cell Physiol Biochem

Background: Peripheral artery disease (PAD) is a major health burden in the world. Stem cell-based therapy has emerged as an attractive treatment option in regenerative medicine. In this study, we sought to test the hypothesis that stem cell-based therapy can ameliorate ischemia induced limb injury. Methods: We isolated mesenchymal stem cells derived from human placentas (PMSCs) and intramuscularly transplanted them into injured hind limbs. Treatment with PMSCs reduced acute muscle fibers apoptosis induced by ischemia. Results: PMSC treatment significantly enhanced regeneration of the injured hind limb by reducing fibrosis and enhancing running capacity when the animals were subjected to treadmill training. Mechanistically, injected PMSCs can modulate acute inflammatory responses by reducing neutrophil and macrophage infiltration following limb ischemia. ELISA assays further confirmed that PMSC treatment can also reduce pro-inflammatory cytokines, TNF-α and IL-6, and enhance anti-inflammatory cytokine, IL-10 at the injury sites. Conclusion: Taken together, our results demonstrated that PMSCs can be a potential effective therapy for treatment of PAD via immunomodulation.

Section: Discussionmentioning

confidence: 99%

Delivery of Placenta-Derived Mesenchymal Stem Cells Ameliorates Ischemia Induced Limb Injury by Immunomodulation

Adesanya

et al. 2014

Cell Physiol Biochem

“…The beneficial effects of MSCs seen with diseases other than lung pathologies suggests that they may be beneficial in treating BO. In a mouse model of heterotopic tracheal transplantation, our group demonstrated the positive effects by bone marrow-derived MSCs on the attenuation of airway obliteration (26), and another group has demonstrated a similar protective effect by placenta-derived MSCs in the heterotopic tracheal transplantation (50). In murine orthotopic tracheal transplantation, MSCs protected as well against allograft rejection, further supporting the promising role of stem cells in BO (51).…”

Section: Bronchiolitis Obliteransmentioning

confidence: 63%

Mesenchymal stem cells for therapy in lung diseases

Álvarez¹

2014

SOB

SummaryLung diseases are among the most devastating illnesses because of their prevalence and simultaneous lack of viable treatment. To advance beyond the current options of mechanical ventilation and transplantation, research in recent years has focused on cell therapy, and of the possibilities, mesenchymal stem cells (MSCs) are the most promising. MSCs have immunomodulatory and secretory effects that work to relieve inflammation and prevent fibrosis in response to the injured lung. Numerous small and large animal models have shown the ameliorating effects of MSCs in diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disorder, acute respiratory distress syndrome, obstructive sleep apnea, bronchiolitis obliterans, and asthma. Clinical trials for MSC use in some of these are in their early stages, but the encouraging promise of this cell therapy will ensure more trials to come. This review will first discuss MSCs as a population with varied properties and mechanisms of action and then will examine the efforts so far to use MSCs as treatment in various lung diseases.

“…The beneficial effects of MSCs from bone marrow and placenta have been reported in animal models of OB by our group and other investigators [19–22]. Although ASCs were reported to be more potent in immunomodulation than bone marrow and placenta MSCs [9–11], the effects and mechanism of ASCs on OB are not understood.…”

Section: Discussionmentioning

confidence: 93%

“…The benefits appear derive from generation of IL-10 and Foxp3+ Treg [19, 22]. Since OB is a chronic disease, the present study is to determine the effects of multiple doses of ASCs on the pathogenesis of OB in a heterotopic tracheal transplantation (HTT) model.…”

Section: Introductionmentioning

confidence: 99%

Human adipose-derived mesenchymal stem cells alleviate obliterative bronchiolitis in a murine model via IDO

Zheng

Qiu

et al. 2017

Respir Res

BackgroundLong-term survival of lung transplantation is hindered by the development of obliterative bronchiolitis (OB). Adipose-derived stem cells (ASCs) were documented to have more potent immunosuppressive ability than mesenchymal stem cells (MSCs) from bone marrow and placenta. The goal of our study is to evaluate the effect of repeated administration of ASCs on OB and the involvement of indoleamine 2,3-dioxygenase (IDO) mediating the protective effect of ASCs in a heterotopic tracheal transplantation (HTT) model.MethodsFor studies in vitro, ASCs were treated with interferon-γ (IFN-γ). For in vivo study, tracheas from BALB/c or C57BL/6 donors were transplanted into C57BL/6 recipients to create a HTT model. On days 0, 1, 3, 5, 8, 12, 15, 20 and 25 post-transplant, the allogeneic recipient mice were administered intravenously with phosphate buffered saline, 1 × 106 human ASCs, or 1 × 106 human ASCs plus 1-methyltryptophan (1-MT), an IDO inhibitor. On days 3, 7, 14 and 28, serum, trachea and spleen samples were harvested for analysis.ResultsASCs homed to heterotopic tracheal grafts after infusion. Multiple doses of ASCs significantly increased tracheal IDO levels in allografts. There were significant increases in graft and serum IFN-γ levels in allografts compared with isografts. IFN-γ elevated IDO expression and activity in ASCs in vitro. ASCs alleviated OB in allografts as evidenced by reduced epithelial loss, epithelial apoptosis, and intraluminal obstruction. The effects of ASCs on OB were blocked by 1-MT. 1-MT also blocked the alterations in pro and anti-inflammatory cytokines as well as CD3+ T cell infiltration induced by ASCs. ASCs induced not only splenic levels of CD4+CD25+Foxp3+ regulatory T cells (Treg) but also IL-10 and TGF-β-producing Treg. Furthermore, IDO inhibition abolished the changes of splenic Treg induced by ASCs. In addition, Treg reduction by cyclophosphamide treatment did not alter the effects of ASCs on tracheal IDO expression in allografts confirming Treg induction is downstream of IDO.ConclusionsRepeated doses of ASCs are capable of ameliorating OB. ASCs act at least in part via elevating IDO expression. ASCs promote the generation of Treg and suppress T cell infiltration via an IDO-dependent mechanism.