MSC Transplantation Attenuates Inflammation, Prevents Endothelial Damage and Enhances the Angiogenic Potency of Endogenous MSCs in a Model of Pulmonary Arterial Hypertension

Shao, Feng-Jin; Li, Rui; Tan, Xiaohong; Zhang, Qiaoyan; Ye, Lujie; Yan, Bingxuan; Zhao, Ying; Xu, Jiaxue

doi:10.2147/jir.s355479

Cited by 9 publications

(8 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Admittedly, angiogenic action is a key point in any type of damage healing for blood-carrying nutrients or metabolic waste products [ 38 ]. Moreover, the morbid state will influence the stem cells’ actions [ 39 , 40 ], causing them to differentiate into endothelial cells to form vessels directly [ 41 ] and promote local cell migration and growth. Recently, protein-rich exosomes of stem cells were found, which could regulate vessel formation, such as VEGF-A [ 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the morbid state will influence the stem cells’ actions [ 39 , 40 ], causing them to differentiate into endothelial cells to form vessels directly [ 41 ] and promote local cell migration and growth. Recently, protein-rich exosomes of stem cells were found, which could regulate vessel formation, such as VEGF-A [ 41 , 42 ]. Secondly, they promote the proliferation and maturation of wound healing cells [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Mesenchymal stem cells transplantation for perianal fistulas: a systematic review and meta-analysis of clinical trials

Wang

Jiang²,

Zhang

et al. 2023

Stem Cell Res Ther

View full text Add to dashboard Cite

Background Perianal fistulas, characterised as granulomatous inflammation of fistulas around the anal canal, are associated with significant morbidity resulting in a negative impact on quality of life and a tremendous burden to the healthcare system. Treatment of anal fistulas usually consists of anal surgery; however, results of closure rates are not satisfactory especially with complex perianal fistulas, after which many patients may suffer from anal incontinence. Recently, the administration of mesenchymal stem cells (MSCs) has shown promising efficacy. Herein, we aim to explore whether MSCs are effective for complex perianal fistulas and if they have either short-term, medium-term, long-term or over-long-term efficacy. Additionally, we want to elucidate whether factors such as drug dosage, MSC source, cell type, and disease aetiology influence treatment efficacy. Main body of the abstract We searched four online databases and analysed data based on information within the clinical trials registry. The outcomes of eligible trials were analysed with Review Manager 5.4.1. Relative risk and related 95% confidence interval were calculated to compare the effect between the MSCs and control groups. In addition, the Cochrane risk of bias tool was applied to evaluate the bias risk of eligible studies. Meta-analyses showed that therapy with MSCs was superior to conventional treatment for complex perianal fistulas in short-, long- and over-long-term follow-up phases. However, there was no statistical difference in treatment efficacy in the medium term between the two methods. Subgroup meta-analyses showed factors including cell type, cell source and cell dosage were superior compared to the control, but there was no significant difference between different experimental groups of those factors. Besides, local MSCs therapy has shown more promising results for fistulas as a result of Crohn’s Disease (CD). Although we tend to maintain that MSCs therapy is effective for cryptoglandular fistulas equally, more studies are needed to confirm this conclusion in the future. Short conclusion MSCs Transplantation could be a new therapeutic method for complex perianal fistulas of both cryptoglandular and CD origin showing high efficacy in the short-term to over-long-term phases, as well as high efficacy in sustained healing. The difference in cell types, cell sources and cell dosages did not influence MSCs’ efficacy.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells transplantation for perianal fistulas: a systematic review and meta-analysis of clinical trials

Wang

Jiang²,

Zhang

et al. 2023

Stem Cell Res Ther

View full text Add to dashboard Cite

show abstract

“…Research has shown that pulmonary arterial pressure in normal broilers increases from 20 to 25 mmHg between 2 and 3 weeks and maintains at approximately 25 mmHg during weeks 4 and 5 of age [ 57 ].Individuals having the most restricted pulmonary vascular capacity develop PAH when their right heart must develop an excessively elevated pulmonary arterial pressure to overcome the increased resistance to flow through the constricted pulmonary arterioles [ 55 ]. Sustained PAH triggers a series of events leading to structural vascular changes similar to the observations in human patients, including medial thickening and intimal proliferation [ 43 , 58 , 59 ]. Despite that fact that PAH broilers demonstrate increased plexiform lesions in their lungs [ 60 ], we and others have shown that PAH is not an essential prerequisite of the structures [ 38 , 39 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

“…We have recently confirmed the presence of eEPCs (CD133+/VEGFR-2+ cells) and foam-like macrophages in the structures, and provided evidence that the lesion development in this avian model is associated with hemodynamic stress [ 41 , 42 ]. More recently, we showed that transplantation of mesenchymal stromal cells attenuates neointimal and plexogenic arteriopathy in PAH broiler chickens through modulating lung inflammation [ 43 ].…”

Section: Introductionmentioning

confidence: 99%

Potential contribution of early endothelial progenitor cell (eEPC)-to-macrophage switching in the development of pulmonary plexogenic lesion

Shao

Guo

et al. 2022

Respir Res

View full text Add to dashboard Cite

Background Plexiform lesions, which have a dynamic appearance in structure and cellular composition, are the histological hallmark of severe pulmonary arterial hypertension in humans. The pathogenesis of the lesion development remains largely unknown, although it may be related to local inflammation and dysfunction in early progenitor endothelial cells (eEPCs). We tested the hypothesis that eEPCs contribute to the development of plexiform lesions by differentiating into macrophages in the setting of chronic inflammation. Methods The eEPC markers CD133 and VEGFR-2, macrophage lineage marker mannose receptor C-type 1 (MRC1), TNFα and nuclear factor erythroid 2-related factor 2 (Nrf2) in plexiform lesions in a broiler model were determined by immunohistochemistry. eEPCs derived from peripheral blood mononuclear cells were exposed to TNFα, and macrophage differentiation and angiogenic capacity of the cells were evaluated by phagocytotic and Matrigel plug assays, respectively. The role of Nrf2 in eEPC-to-macrophage transition as well as in MRC1 expression was also evaluated. Intratracheal installation of TNFα was conducted to determine the effect of local inflammation on the formation of plexiform lesions. Results Cells composed of the early lesions have a typical eEPC phenotype whereas those in more mature lesions display molecular and morphological characteristics of macrophages. Increased TNFα production in plexiform lesions was observed with lesion progression. In vitro studies showed that chronic TNFα challenge directed eEPCs to macrophage differentiation accompanied by hyperactivation of Nrf2, a stress-responsive transcription factor. Nrf2 activation (Keap1 knockdown) caused a marked downregulation in CD133 but upregulation in MRC1 mRNA. Dual luciferase reporter assay demonstrated that Nrf2 binds to the promoter of MRC1 to trigger its expression. In good agreement with the in vitro observation, TNFα exposure induced macrophage differentiation of eEPCs in Matrigel plugs, resulting in reduced neovascularization of the plugs. Intratracheal installation of TNFα resulted in a significant increase in plexiform lesion density. Conclusions This work provides evidence suggesting that macrophage differentiation of eEPCs resulting from chronic inflammatory stimulation contributes to the development of plexiform lesions. Given the key role of Nrf2 in the phenotypic switching of eEPCs to macrophages, targeting this molecular might be beneficial for intervention of plexiform lesions.

show abstract

“…However, these methods are usually not very satisfactory, approximately 40% of patients progressing to total hip arthroplasty [5][6][7][8]. MSCs are considered to be an ideal material for bone regeneration and vascular regeneration because of its differentiation potency [9,10].…”

Section: Introductionmentioning

confidence: 99%

Runx2 overexpression promotes bone repair of osteonecrosis of the femoral head (ONFH)

Liu

et al. 2023

Mol Biol Rep

View full text Add to dashboard Cite

Background Runt-related transcription factor-2 (Runx2) has been considered an inducer to improve bone repair ability of mesenchymal stem cells (MSCs). Methods and results Twenty-four rabbits were used to establish Osteonecrosis of the femoral head (ONFH) and randomly devided into four groups: Adenovirus Runx2 (Ad-Runx2) group, Runx2-siRNA group, MSCs group and Model group. At 1 week after model establishment, the Ad-Runx2 group was treated with 5 × 107 MSCs transfected through Ad-Runx2, the Runx2-siRNA group was treated with 5 × 107 MSCs transfected through Runx2-siRNA, the MSCs group was injected with 5 × 107 untreated MSCs, and the Model group was treated with saline. The injection was administered at 1 week and 3 weeks after model establishment. The expression of bone morphogenetic protein 2 (BMP-2), Runx2 and Osterix from the femoral head was detected at 3 and 6 weeks after MSCs being injected, and Masson Trichrome Staining, Gross Morphology, X-ray and CT images observation were used to evaluate the repair effect of ONFH. The data revealed that the expression of BMP-2, Runx2 and Osterix in the Runx2-siRNA group was reduced at 3 weeks compared with the MSCs group, and then the expression further reduced at 6 weeks, but was still higher than the Model group besides Osterix; The expression of these three genes in the Ad-Runx2 group was higher than in the MSCs group. Masson Trichrome Staining, Gross Morphology and X-ray and CT images observation revealed that necrotic femoral head of the MSCs group was more regular and smooth than the Runx2-siRNA group, which has a collapsed and irregular femoral head. In the Ad-Runx2 group, necrotic femoral head was basically completely repaired and covered by rich cartilage and bone tissue. Conclusions Overexpression of Runx2 can improve osteoblastic phenotype maintenance of MSCs and promote necrotic bone repair of ONFH.

show abstract

MSC Transplantation Attenuates Inflammation, Prevents Endothelial Damage and Enhances the Angiogenic Potency of Endogenous MSCs in a Model of Pulmonary Arterial Hypertension

Cited by 9 publications

References 59 publications

Mesenchymal stem cells transplantation for perianal fistulas: a systematic review and meta-analysis of clinical trials

Mesenchymal stem cells transplantation for perianal fistulas: a systematic review and meta-analysis of clinical trials

Potential contribution of early endothelial progenitor cell (eEPC)-to-macrophage switching in the development of pulmonary plexogenic lesion

Runx2 overexpression promotes bone repair of osteonecrosis of the femoral head (ONFH)

Contact Info

Product

Resources

About