Mesenchymal Stem Cells as Endogenous Regulators of Inflammation

Munir, Hafsa; Ward, Lewis S. C.; McGettrick, Helen M.

doi:10.1007/978-3-319-78127-3_5

Cited by 27 publications

(17 citation statements)

References 145 publications

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“…Nowadays, many different anti-inflammatory therapies, aimed to modulate an adverse and unbalanced inflammation, are under evaluation [4]. Among them, cell therapy has become a valuable tool since stem cells have proved to exert an immunomodulatory effect on different immune mediated diseases [5,6]. In relation to myocardial infarction, the intracoronary delivery of cardiosphere-derived cells (CDCs) has already been found to attenuate myocardial inflammation in a murine model of autoimmune myocarditis [7], and to reverse inflammation and fibrosis in hypertensive rats [8].…”

Section: Introductionmentioning

confidence: 99%

The Intrapericardial Delivery of Extracellular Vesicles from Cardiosphere-Derived Cells Stimulates M2 Polarization during the Acute Phase of Porcine Myocardial Infarction

López

Blázquez

Marinaro

et al. 2019

Stem Cell Rev and Rep

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Acute myocardial infarction triggers a strong inflammatory response in the affected cardiac tissue. New therapeutic tools based on stem cell therapy may modulate the unbalanced inflammation in the damaged cardiac tissue, contributing to the resolution of this pathological condition. The main goal of this study was to analyze the immunomodulatory effects of cardiosphere-derived cells (CDCs) and their extracellular vesicles (EV-CDCs), delivered by intrapericardial administration in a clinically relevant animal model, during the initial pro-inflammatory phase of an induced myocardial infarction. This effect was assessed in peripheral blood and pericardial fluid leukocytes from infarcted animals. Additionally, cardiac functional parameters, troponin I, hematological and biochemical components were also analyzed to characterize myocardial infarction-induced changes, as well as the safety aspects of these procedures. Our preclinical study demonstrated a successful myocardial infarction induction in all animals, without any reported adverse effect related to the intrapericardial administration of CDCs or EV-CDCs. Significant changes were observed in biochemical and immunological parameters after myocardial infarction. The analysis of peripheral blood leukocytes revealed an increase of M2 monocytes in the EV-CDCs group, while no differences were reported in other lymphocyte subsets. Moreover, arginase-1 (M2-differentiation marker) was significantly increased in pericardial fluids 24 h after EV-CDCs administration. In summary, we demonstrate that, in our experimental conditions, intrapericardially administered EV-CDCs have an immunomodulatory effect on monocyte polarization, showing a beneficial effect for counteracting an unbalanced inflammatory reaction in the acute phase of myocardial infarction. These M2 monocytes have been defined as "pro-regenerative cells" with a pro-angiogenic and anti-inflammatory activity.

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Section: Introductionmentioning

confidence: 99%

The Intrapericardial Delivery of Extracellular Vesicles from Cardiosphere-Derived Cells Stimulates M2 Polarization during the Acute Phase of Porcine Myocardial Infarction

López

Blázquez

Marinaro

et al. 2019

Stem Cell Rev and Rep

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“…In addition to immune cells and tissue cells, tissue-resident stem cells, especially mesenchymal stromal cells (MSCs), are also affected by cellular senescence 17 . Similar to other adult stem cells, MSCs possess a limited capacity of self-renewal.…”

Section: Inflammagingmentioning

confidence: 99%

Age-related cerebral small vessel disease and inflammaging

Huang

Cai

et al. 2020

Cell Death Dis

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The continued increase in global life expectancy predicts a rising prevalence of age-related cerebral small vessel diseases (CSVD), which requires a better understanding of the underlying molecular mechanisms. In recent years, the concept of “inflammaging” has attracted increasing attention. It refers to the chronic sterile low-grade inflammation in elderly organisms and is involved in the development of a variety of age-related chronic diseases. Inflammaging is a long-term result of chronic physiological stimulation of the immune system, and various cellular and molecular mechanisms (e.g., cellular senescence, immunosenescence, mitochondrial dysfunction, defective autophagy, metaflammation, gut microbiota dysbiosis) are involved. With the deepening understanding of the etiological basis of age-related CSVD, inflammaging is considered to play an important role in its occurrence and development. One of the most critical pathophysiological mechanisms of CSVD is endothelium dysfunction and subsequent blood-brain barrier (BBB) leakage, which gives a clue in the identification of the disease by detecting circulating biological markers of BBB disruption. The regional analysis showed blood markers of vascular inflammation are often associated with deep perforating arteriopathy (DPA), while blood markers of systemic inflammation appear to be associated with cerebral amyloid angiopathy (CAA). Here, we discuss recent findings in the pathophysiology of inflammaging and their effects on the development of age-related CSVD. Furthermore, we speculate the inflammaging as a potential target for future therapeutic interventions to delay or prevent the progression of the age-related CSVD.

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“…The anti-inflammatory property enforces the most prominent beneficial effects of MSC-based therapies, which has been discussed in detail in a few excellent reviews (Prockop and Oh, 2012;Wang et al, 2016;Regulski, 2017;Munir et al, 2018). Despite the initial lung entrapment, exogenously administered MSCs migrate along cytokine gradients toward inflamed tissue and home to sites of injury, where they suppress inflammation in their local environments (Rustad and Gurtner, 2012).…”

Section: Mscs Function As Guardians Of Inflammation During Granulatiomentioning

confidence: 99%

Mesenchymal Stem Cells Adaptively Respond to Environmental Cues Thereby Improving Granulation Tissue Formation and Wound Healing

Jiang

Scharffetter‐Kochanek

2020

Front. Cell Dev. Biol.

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Granulation tissue formation constitutes a key step during wound healing of the skin and other organs. Granulation tissue concomitantly initiates regenerative M2 macrophages polarization, fibroblast proliferation, myofibroblast differentiation with subsequent contraction of the wound, new vessel formation, and matrix deposition. Impaired granulation tissue formation either leads to delayed wound healing or excessive scar formation, conditions with high morbidity and mortality. Accumulating evidence has demonstrated that mesenchymal stem cell (MSC)-based therapy is a promising strategy to ameliorate defects in granulation tissue formation and to successfully treat non-healing chronic wounds. In this review we give an updated overview of how therapeutically administered MSCs ensure a balanced granulation tissue formation, and furthermore discuss the cellular and molecular mechanisms underlying the adaptive responses of MSCs to cue in their direct neighborhood. Improved understanding of the interplay between the exogenous MSCs and their niche in granulation tissue will foster the development of MSC-based therapies tailored for difficult-to-treat nonhealing wounds.

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Mesenchymal Stem Cells as Endogenous Regulators of Inflammation

Cited by 27 publications

References 145 publications

The Intrapericardial Delivery of Extracellular Vesicles from Cardiosphere-Derived Cells Stimulates M2 Polarization during the Acute Phase of Porcine Myocardial Infarction

The Intrapericardial Delivery of Extracellular Vesicles from Cardiosphere-Derived Cells Stimulates M2 Polarization during the Acute Phase of Porcine Myocardial Infarction

Age-related cerebral small vessel disease and inflammaging

Mesenchymal Stem Cells Adaptively Respond to Environmental Cues Thereby Improving Granulation Tissue Formation and Wound Healing

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