Increased Antioxidant Defense Mechanism in Human Adventitia-Derived Progenitor Cells Is Associated with Therapeutic Benefit in Ischemia

Iacobazzi, Dominga; Mangialardi, Giuseppe; Gubernator, Miriam; Hofner, Manuela; Wielscher, Matthias; Vierlinger, Klemens; Reni, Carlotta; Oikawa, Atsuhiko; Spinetti, Gaia; Vono, Rosa; Sangalli, Elena; Montagnani, Monica; Madeddu, Paolo

doi:10.1089/ars.2013.5404

Cited by 29 publications

(32 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This result is consistent with our previous findings documenting the peculiar resilience of SVPs to ischemic stress. 12,29 Clusters of human CSCs could be also detected in the recipient heart, although they were not present in all the samples and were less abundant than SVPs (Online Figure IVB, IVE, and IVF). In hearts receiving combined cell therapy (in which cells were labeled with DiL and DiO), we did not observe increased engraftment or spatial connections between SVPs and CSCs.…”

Section: Engraftment and In Vivo Differentiation Of Transplanted Cellsmentioning

confidence: 95%

Combined Intramyocardial Delivery of Human Pericytes and Cardiac Stem Cells Additively Improves the Healing of Mouse Infarcted Hearts Through Stimulation of Vascular and Muscular Repair

Avolio

Meloni

Spencer

et al. 2015

Circulation Research

Self Cite

118

127

View full text Add to dashboard Cite

Rationale: Optimization of cell therapy for cardiac repair may require the association of different cell populations with complementary activities. Objective: Compare the reparative potential of saphenous vein–derived pericytes (SVPs) with that of cardiac stem cells (CSCs) in a model of myocardial infarction, and investigate whether combined cell transplantation provides further improvements. Methods and Results: SVPs and CSCs were isolated from vein leftovers of coronary artery bypass graft surgery and discarded atrial specimens of transplanted hearts, respectively. Single or dual cell therapy (300 000 cells of each type per heart) was tested in infarcted SCID (severe combined immunodeficiency)-Beige mice. SVPs and CSCs alone improved cardiac contractility as assessed by echocardiography at 14 days post myocardial infarction. The effect was maintained, although attenuated at 42 days. At histological level, SVPs and CSCs similarly inhibited infarct size and interstitial fibrosis, SVPs were superior in inducing angiogenesis and CSCs in promoting cardiomyocyte proliferation and recruitment of endogenous stem cells. The combination of cells additively reduced the infarct size and promoted vascular proliferation and arteriogenesis, but did not surpass single therapies with regard to contractility indexes. SVPs and CSCs secrete similar amounts of hepatocyte growth factor, vascular endothelial growth factor, fibroblast growth factor, stem cell factor, and stromal cell–derived factor-1, whereas SVPs release higher quantities of angiopoietins and microRNA-132. Coculture of the 2 cell populations results in competitive as well as enhancing paracrine activities. In particular, the release of stromal cell–derived factor-1 was synergistically augmented along with downregulation of stromal cell–derived factor-1–degrading enzyme dipeptidyl peptidase 4. Conclusions: Combinatory therapy with SVPs and CSCs may complementarily help the repair of infarcted hearts.

show abstract

Section: Engraftment and In Vivo Differentiation Of Transplanted Cellsmentioning

confidence: 95%

Combined Intramyocardial Delivery of Human Pericytes and Cardiac Stem Cells Additively Improves the Healing of Mouse Infarcted Hearts Through Stimulation of Vascular and Muscular Repair

Avolio

Meloni

Spencer

et al. 2015

Circulation Research

Self Cite

118

127

View full text Add to dashboard Cite

show abstract

“…Maddedu and colleagues 153,155,156 have taken steps toward the therapeutic use of human saphenous vein-derived adventitial progenitor cells with the ultimate objective of refining these cells into a clinical grade product to treat ischemic heart disease. Using in vitro and preclinical model systems, they demonstrated the resilience of adventitial progenitor cells to oxidative stress through upregulated expression of antioxidant and detoxifier enzymes (eg, superoxide dismutase and catalase), which may facilitate their capacity to promote angiogenesis and to improve tissue perfusion in the face of ischemia.…”

Section: 98mentioning

confidence: 99%

“…Using in vitro and preclinical model systems, they demonstrated the resilience of adventitial progenitor cells to oxidative stress through upregulated expression of antioxidant and detoxifier enzymes (eg, superoxide dismutase and catalase), which may facilitate their capacity to promote angiogenesis and to improve tissue perfusion in the face of ischemia. 155 They have also recently performed comparisons of numerous adventitial progenitor cell lines from left over saphenous vein tissue at coronary bypass surgery and varicose vein removal. 156 These lines were expanded to therapeutic levels of 30 to 50×10 6 cells within ≈10 weeks, with conservation of phenotypic and functional properties and low levels of replicative senescence during subculture.…”

Section: 98mentioning

confidence: 99%

Vascular Wall Progenitor Cells in Health and Disease

Psaltis

Simari

2015

Circulation Research

173

155

View full text Add to dashboard Cite

The vasculature plays an indispensible role in organ development and maintenance of tissue homeostasis, such that disturbances to it impact greatly on developmental and postnatal health. Although cell turnover in healthy blood vessels is low, it increases considerably under pathological conditions. The principle sources for this phenomenon have long been considered to be the recruitment of cells from the peripheral circulation and the re-entry of mature cells in the vessel wall back into cell cycle. However, recent discoveries have also uncovered the presence of a range of multipotent and lineage-restricted progenitor cells in the mural layers of postnatal blood vessels, possessing high proliferative capacity and potential to generate endothelial, smooth muscle, hematopoietic or mesenchymal cell progeny. In particular, the tunica adventitia has emerged as a progenitor-rich compartment with niche-like characteristics that support and regulate vascular wall progenitor cells. Preliminary data indicate the involvement of some of these vascular wall progenitor cells in vascular disease states, adding weight to the notion that the adventitia is integral to vascular wall pathogenesis, and raising potential implications for clinical therapies. This review discusses the current body of evidence for the existence of vascular wall progenitor cell subpopulations from development to adulthood and addresses the gains made and significant challenges that lie ahead in trying to accurately delineate their identities, origins, regulatory pathways, and relevance to normal vascular structure and function, as well as disease.

show abstract

“…Anti-oxidant molecules may protect from endothelial dysfunction by re-coupling eNOS activity, reduce superoxide production, increase the activity of superoxide scavenging enzymes, or decrease vascular NAD(P)H oxidase activity [251,252]. Novel antioxidant therapies aiming to restore production of endothelialderived NO or to act as endogenous antioxidant enzymes may represent a more targeted strategy focusing specifically on the mechanisms implicated in diabetes-induced endothelial dysfunction (reviewed in [240].…”

Section: Rock (Rho-associated Kinase) Inhibitors -mentioning

confidence: 99%

Targeting endothelial metaflammation to counteract diabesity cardiovascular risk: Current and perspective therapeutic options

Potenza

Nacci

Salvia

et al. 2017

Pharmacological Research

Self Cite

View full text Add to dashboard Cite

Abstract:The association of obesity and diabetes, termed "diabesity", defines a combination of primarily metabolic disorders with insulin resistance as the underlying common pathophysiology. Cardiovascular disorders associated with diabesity represent the leading cause of morbidity and mortality in the Western world. This makes diabesity, with its rising impacts on both health and economics, one of the most challenging biomedical and social threats of present century. The emerging comprehension of the genes whose alteration confers inter-individual differences on risk factors for diabetes or obesity, together with the potential role of genetically determined variants on mechanisms controlling responsiveness, effectiveness and safety of anti-diabetic therapy underlines the need of additional knowledge on molecular mechanisms involved in the pathophysiology of diabesity. Endothelial cell dysfunction, resulting from the unbalanced production of endothelialderived vascular mediators, is known to be present at the earliest stages of insulin resistance and obesity, and may precede the clinical diagnosis of diabetes by several years. Once considered as a mere consequence of metabolic abnormalities, it is now clear that endothelial dysfunctional activity may play a pivotal role in the progression of diabesity. In the vicious circle where vascular defects and metabolic disturbances worsen and reinforce each other, a low-grade, chronic, and 'cold' inflammation (metaflammation) has been suggested to serve as the pathophysiological link that binds endothelial and metabolic dysfunctions. In this paradigm, it is important to consider how traditional antidiabetic treatments (specifically addressing metabolic dysregulation) may directly impact on inflammatory processes or cardiovascular function. Indeed, not all drugs currently available to treat diabetes possess the same anti-inflammatory potential, or target endothelial cell function equally. Perspective strategies pointing at reducing metaflammation or directly addressing endothelial dysfunction may disclose beneficial consequences on metabolic regulation. This review focuses on existing and potential new approaches ameliorating endothelial dysfunction and vascular inflammation in the context of diabesity.

show abstract

Increased Antioxidant Defense Mechanism in Human Adventitia-Derived Progenitor Cells Is Associated with Therapeutic Benefit in Ischemia

Abstract: APCs from vein remnants of CABG patients express antioxidant defense mechanisms, which enable them to resist stress. These properties highlight the potential of APCs in cardiovascular regenerative medicine.

Cited by 29 publications

References 37 publications

Combined Intramyocardial Delivery of Human Pericytes and Cardiac Stem Cells Additively Improves the Healing of Mouse Infarcted Hearts Through Stimulation of Vascular and Muscular Repair

Combined Intramyocardial Delivery of Human Pericytes and Cardiac Stem Cells Additively Improves the Healing of Mouse Infarcted Hearts Through Stimulation of Vascular and Muscular Repair

Vascular Wall Progenitor Cells in Health and Disease

Targeting endothelial metaflammation to counteract diabesity cardiovascular risk: Current and perspective therapeutic options

Contact Info

Product

Resources

About