Healing the Broken Heart; The Immunomodulatory Effects of Stem Cell Therapy

Wagner, Marcus; Khan, Mohsin; Mohsin, Sadia

doi:10.3389/fimmu.2020.00639

Cited by 31 publications

(20 citation statements)

References 223 publications

(243 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Following the initial inflammatory phase, the expansion of neutrophil and macrophage populations facilitates phagocytosis and clearance of the dead cells, and release of cytokines and growth factors. This leads to the initiation of the healing process via the activation of myofibroblast proliferation and neovascularization of the injured myocardium [ 14 ].…”

Section: Cardiac Immune Cellsmentioning

confidence: 99%

Role of Cardiac Macrophages on Cardiac Inflammation, Fibrosis and Tissue Repair

Lafuse

Wozniak

Rajaram

2020

Cells

213

175

View full text Add to dashboard Cite

The immune system plays a pivotal role in the initiation, development and resolution of inflammation following insult or damage to organs. The heart is a vital organ which supplies nutrients and oxygen to all parts of the body. Heart failure (HF) has been conventionally described as a disease associated with cardiac tissue damage caused by systemic inflammation, arrhythmia and conduction defects. Cardiac inflammation and subsequent tissue damage is orchestrated by the infiltration and activation of various immune cells including neutrophils, monocytes, macrophages, eosinophils, mast cells, natural killer cells, and T and B cells into the myocardium. After tissue injury, monocytes and tissue-resident macrophages undergo marked phenotypic and functional changes, and function as key regulators of tissue repair, regeneration and fibrosis. Disturbance in resident macrophage functions such as uncontrolled production of inflammatory cytokines, growth factors and inefficient generation of an anti-inflammatory response or unsuccessful communication between macrophages and epithelial and endothelial cells and fibroblasts can lead to aberrant repair, persistent injury, and HF. Therefore, in this review, we discuss the role of cardiac macrophages on cardiac inflammation, tissue repair, regeneration and fibrosis.

show abstract

Section: Cardiac Immune Cellsmentioning

confidence: 99%

Role of Cardiac Macrophages on Cardiac Inflammation, Fibrosis and Tissue Repair

Lafuse

Wozniak

Rajaram

2020

Cells

213

175

View full text Add to dashboard Cite

show abstract

“…In the first stage, the injured myocardium releases damage associated molecular patterns (DAMPs), which bind toll-like receptors (TLRs), and initiate the production of cytokines/chemokines to induce the activation and recruitment of neutrophils and Ly6C high monocytes. Some Ly6C high monocytes differentiate into M1 macrophages, which contain a pro-inflammatory secretome enriched in interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6 [11]. In the second stage, Ly6C low monocytes and M2-like macrophages with high expression of IL-10, transforming growth factor (TGF)-β and vascular endothelial growth factor (VEGF) come in with the anti-inflammatory function much needed after injury [16].…”

Section: Immune Cell Response Post-ischemic Injurymentioning

confidence: 99%

“…However, sustained T cell responses in the heart can lead to adverse remodeling and contribute to the progression of ischemic heart failure (HF) at later chronic stages [10]. Temporal and spatial regulation from these biphasic immune cell populations is essential to maintain reparative processes [11]. Importantly, focusing on T cells, including Tregs, can be a clue to reveal the reparative mechanism.…”

Section: Introductionmentioning

confidence: 99%

The Regulatory Role of T Cell Responses in Cardiac Remodeling Following Myocardial Infarction

Kino

Khan

Mohsin

2020

IJMS

Self Cite

View full text Add to dashboard Cite

Ischemic injury to the heart causes cardiomyocyte and supportive tissue death that result in adverse remodeling and formation of scar tissue at the site of injury. The dying cardiac tissue secretes a variety of cytokines and chemokines that trigger an inflammatory response and elicit the recruitment and activation of cardiac immune cells to the injury site. Cell-based therapies for cardiac repair have enhanced cardiac function in the injured myocardium, but the mechanisms remain debatable. In this review, we will focus on the interactions between the adoptively transferred stem cells and the post-ischemic environment, including the active components of the immune/inflammatory response that can mediate cardiac outcome after ischemic injury. In particular, we highlight how the adaptive immune cell response can mediate tissue repair following cardiac injury. Several cell-based studies have reported an increase in pro-reparative T cell subsets after stem cell transplantation. Paracrine factors secreted by stem cells polarize T cell subsets partially by exogenous ubiquitination, which can induce differentiation of T cell subset to promote tissue repair after myocardial infarction (MI). However, the mechanism behind the polarization of different subset after stem cell transplantation remains poorly understood. In this review, we will summarize the current status of immune cells within the heart post-MI with an emphasis on T cell mediated reparative response after ischemic injury.

show abstract

“…Cardiac cell-based therapies aimed at regeneration and/or instructing a more favorable repair have been explored in clinical settings, including skeletal myoblasts, embryonic stem cells (ESCs), bone marrow mononuclear cells (BMMNCs), cardiac stem cells (CSCs), hematopoietic stem cells (HSCs), mesenchymal stromal cells (MSCs), and recently, induced pluripotent stem cells (iPSCs)-derived cardiomyocytes in pre-clinical studies (Madigan and Atoui, 2018 ). The existence of CSCs in the adult myocardium has raised controversy in particular what concerns their capacity to generate cardiomyocytes (Valente et al, 2014 ; Maliken and Molkentin, 2018 ), as their therapeutic effect has been associated to immunomodulatory and paracrine mechanisms also observed in human MSCs (Wagner et al, 2020 ). Indeed, envisioning the development of a universal and feasible therapy, MSCs are of particular interest (Ballini et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Consistent Long-Term Therapeutic Efficacy of Human Umbilical Cord Matrix-Derived Mesenchymal Stromal Cells After Myocardial Infarction Despite Individual Differences and Transient Engraftment

Laundos

Vasques‐Nóvoa

Gomes

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Human mesenchymal stem cells gather special interest as a universal and feasible add-on therapy for myocardial infarction (MI). In particular, human umbilical cord matrix-derived mesenchymal stromal cells (UCM-MSC) are advantageous since can be easily obtained and display high expansion potential. Using isolation protocols compliant with cell therapy, we previously showed UCM-MSC preserved cardiac function and attenuated remodeling 2 weeks after MI. In this study, UCM-MSC from two umbilical cords, UC-A and UC-B, were transplanted in a murine MI model to investigate consistency and durability of the therapeutic benefits. Both cellular products improved cardiac function and limited adverse cardiac remodeling 12 weeks post-ischemic injury, supporting sustained and long-term beneficial therapeutic effect. Donor associated variability was found in the modulation of cardiac remodeling and activation of the Akt-mTOR-GSK3β survival pathway. In vitro, the two cell products displayed similar ability to induce the formation of vessel-like structures and comparable transcriptome in normoxia and hypoxia, apart from UCM-MSCs proliferation and expression differences in a small subset of genes associated with MHC Class I. These findings support that UCM-MSC are strong candidates to assist the treatment of MI whilst calling for the discussion on methodologies to characterize and select best performing UCM-MSC before clinical application.

show abstract

Healing the Broken Heart; The Immunomodulatory Effects of Stem Cell Therapy

Cited by 31 publications

References 223 publications

Role of Cardiac Macrophages on Cardiac Inflammation, Fibrosis and Tissue Repair

Role of Cardiac Macrophages on Cardiac Inflammation, Fibrosis and Tissue Repair

The Regulatory Role of T Cell Responses in Cardiac Remodeling Following Myocardial Infarction

Consistent Long-Term Therapeutic Efficacy of Human Umbilical Cord Matrix-Derived Mesenchymal Stromal Cells After Myocardial Infarction Despite Individual Differences and Transient Engraftment

Contact Info

Product

Resources

About