A Tumor Necrosis Factor-α and Hypoxia-Induced Secretome Therapy for Myocardial Repair

Selvasandran, Kaviyanka; Makhoul, Georges; Jaiswal, Prashant Kumar; Jurakhan, Rishi; Li, Li; Ridwan, Khalid; Cecere, Renzo

doi:10.1016/j.athoracsur.2017.09.005

Cited by 43 publications

(39 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It has been well elucidated that rat BMSCs can secrete paracrine factors including VEGF-1 to trigger angiogenic and migratory effects at the site of the infarct to promote myocardial healing and to improve the cardiac function [39]. In the current study, we also found that the level of VEGF and MVD in the infarct zone had a signi cant increasement after BMSCs transplantation, indicating that paracrine effect plays an essential role in BMSCs tissue repair and angiogenesis.…”

Section: Discussionsupporting

confidence: 68%

Localized Co-delivery of Serca2a and Cx43 Genes Combined With Bone Marrow Mesenchymal Stem Cells Restores Rat Ischemic Cardiac Mechano-electrical Function

Wang¹,

Tayier²,

Guan³

et al. 2020

Preprint

View full text Add to dashboard Cite

Aim: Significantly reduced expression of Ca2+-ATPase 2a (SERCA2a) and Connexin 43 (Cx43) which play important roles in regulating mechano-electrical function was found in an ischemic heart. Bone marrow mesenchymal stem cells (BMSCs) transplantation brings with a weak improvement of ischemic heart in cardiac contractility and anti-arrhythmias effect. The aim of this study was to recover mechano-electrical function of ischemic heart through combining stem cell therapy with SERCA2a/Cx43 co-delivery by biotinylated microbubbles (BMBs) via ultrasound targeted microbubble destruction (UTMD).Methods: Dual gene-loaded BMBs were developed through conjugating SERCA2a-adenovirous (S-Ad) and Cx43-adenovious (C-Ad) onto BMBs via biotin-avidin linkage. UTMD was used to mediate the local co-delivery of S-Ad and C-Ad into the infarct zone where BMSCs were transplanted. The expression of SERCA2a and Cx43 gene, neovascularization in the infarct area and mechano-electrical function of rats were detected. Results: UTMD-mediated dual gene delivery could significantly enhance the expression of SERCA2a/Cx43 genes in the infarct zone receiving BMSCs transplantation. Significantly improved neovascularization was observed. More importantly, UTMD-mediated dual gene delivery greatly improved cardiac function and reduced arrhythmia in these myocardial infarct (MI) hearts transplanted with BMSCs. Conclusions: BMSCs-based dual gene therapy can effectively improve cardiac mechano-electrical function and reduce arrhythmia in heart with MI. It is necessary to rebuild the gene network in damaged heart rather than supply a single gene. BMSCs transplantation combined with localized dual-gene delivery by UTMD might point out a novel strategy to recover mechano-electrical function of ischemic heart.

show abstract

Section: Discussionsupporting

confidence: 68%

Localized Co-delivery of Serca2a and Cx43 Genes Combined With Bone Marrow Mesenchymal Stem Cells Restores Rat Ischemic Cardiac Mechano-electrical Function

Wang¹,

Tayier²,

Guan³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Currently, a number of studies have shown that transplanting MSCs in vivo can increase injured site closure by secreting paracrine factors, which are beneficial to the healing of damaged tissue (Table 3). For example, after myocardial infarction, rat BMSCs secrete paracrine factors (TGF-β, FGF-2, angiopoietin-2, VEGF-1) to trigger angiogenic and migratory effects at the site of the infarct to promote myocardial healing and improve the cardiac function [1]. In a NOD/SCID mouse model, the transplanted BMSCs secreted nerve growth factor (NGF), HGF, and anti-inflammatory molecules (IL-10, IL1-RA), which contribute to the prevention of apoptosis and increase cell proliferation in the damaged liver [84].…”

Section: Mechanisms Of Bmscs In Tissue Repairmentioning

confidence: 99%

“…Mesenchymal stem cells (MSCs) represent an important source for cell therapy in regenerative medicine. MSCs have shown promising results for repairing damaged tissues in various degenerative diseases, both in animal models and in human clinical trials [1,2,3,4,5,6]. MSCs have a homing ability, meaning that they can migrate into injured sites, and they possess the capacity to differentiate into local components of injured sites and the ability to secrete chemokines, cytokines, and growth factors that help in tissue regeneration [7,8,9,10].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cell Migration and Tissue Repair

Halim

et al. 2019

Cells

646

508

View full text Add to dashboard Cite

Mesenchymal stem cells (MSCs) are multilineage cells with the ability to self-renew and differentiate into a variety of cell types, which play key roles in tissue healing and regenerative medicine. Bone marrow-derived mesenchymal stem cells (BMSCs) are the most frequently used stem cells in cell therapy and tissue engineering. However, it is prerequisite for BMSCs to mobilize from bone marrow and migrate into injured tissues during the healing process, through peripheral circulation. The migration of BMSCs is regulated by mechanical and chemical factors in this trafficking process. In this paper, we review the effects of several main regulatory factors on BMSC migration and its underlying mechanism; discuss two critical roles of BMSCs—namely, directed differentiation and the paracrine function—in tissue repair; and provide insight into the relationship between BMSC migration and tissue repair, which may provide a better guide for clinical applications in tissue repair through the efficient regulation of BMSC migration.

show abstract

“…TNFR1 signaling can also increase PGE2 secretion by inducing COX2 expression in mouse or human BM-MSCs, which in turn reprograms host macrophages to increase IL-10 production thus inhibiting inflammation in a mouse sepsis model and experimental allergic conjunctivitis ( 117 , 118 ). In addition, it has been shown that other immunosuppressive molecules, growth factors, and chemokines such as TSG-6, TGFβ, and IL-8 were produced by TNF-primed MSCs to attenuate the symptoms in diseases including EAE, myocardial infarction, ischemic hind limb, and cutaneous wound probably via TNFR1 signaling pathway ( 122 , 135 , 139 , 141 ). TNF can also induce TNT formation between iPSC-derived MSC and cardiomyocytes for mitochondria transfer to attenuate the damage in mouse anthracycline-induced cardiomyopathy, which is regulated by TNF/NFκB/TNF-IP2 signaling pathway ( 129 ).…”

Section: Tnf Regulation Of Msc Efficacy On Autoimmune and Inflammatormentioning

confidence: 99%

Critical Role of Tumor Necrosis Factor Signaling in Mesenchymal Stem Cell-Based Therapy for Autoimmune and Inflammatory Diseases

Zheng

2018

Front. Immunol.

View full text Add to dashboard Cite

Mesenchymal stem cells (MSCs) have been broadly used as a therapy for autoimmune disease in both animal models and clinical trials. MSCs inhibit T effector cells and many other immune cells, while activating regulatory T cells, thus reducing the production of pro-inflammatory cytokines, including tumor necrosis factor (TNF), and repressing inflammation. TNF can modify the MSC effects via two TNF receptors, i.e., TNFR1 in general mediates pro-inflammatory effects and TNFR2 mediates anti-inflammatory effects. In the central nervous system, TNF signaling plays a dual role, which enhances inflammation via TNFR1 on immune cells while providing cytoprotection via TNFR2 on neural cells. In addition, the soluble form of TNFR1 and membrane-bound TNF also participate in the regulation to fine-tune the functions of target cells. Other factors that impact TNF signaling and MSC functions include the gender of the host, disease course, cytokine concentrations, and the length of treatment time. This review will introduce the fascinating progress in this aspect of research and discuss remaining questions and future perspectives.

show abstract

A Tumor Necrosis Factor-α and Hypoxia-Induced Secretome Therapy for Myocardial Repair

Cited by 43 publications

References 21 publications

Localized Co-delivery of Serca2a and Cx43 Genes Combined With Bone Marrow Mesenchymal Stem Cells Restores Rat Ischemic Cardiac Mechano-electrical Function

Localized Co-delivery of Serca2a and Cx43 Genes Combined With Bone Marrow Mesenchymal Stem Cells Restores Rat Ischemic Cardiac Mechano-electrical Function

Mesenchymal Stem Cell Migration and Tissue Repair

Critical Role of Tumor Necrosis Factor Signaling in Mesenchymal Stem Cell-Based Therapy for Autoimmune and Inflammatory Diseases

Contact Info

Product

Resources

About