Allogenic adipose-derived stem cell therapy overcomes ischemia-induced microvessel rarefaction in the myocardium: systems biology study

Vilahur, Gemma; Oñate, Blanca; Cubedo, Judit; Béjar, Maria Teresa; Arderiu, Gemma; Peña, Esther; Gutiérrez, Manuel; Capdevila, Antoni; Pons-Lladó, Ġuillem; Carreras, Francesc; Hidalgo, Alberto; Badimon, Lina

doi:10.1186/s13287-017-0509-2

Cited by 24 publications

(19 citation statements)

References 51 publications

(66 reference statements)

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“…Pigs have consequently been broadly used to evaluate novel vascular therapies. 46 Recent studies include the intracoronary administration of pASCs after an acute myocardial infarction model [47][48][49] and the transplantation of pASCs cell sheets in a porcine model of chronic heart failure. 50 The structures of porcine and human skin are similar, making pigs a suitable model for dermatologic preclinical studies.…”

Section: Applications In Preclinical Modelsmentioning

confidence: 99%

Properties of porcine adipose-derived stem cells and their applications in preclinical models

Arrizabalaga

Nollert

2017

Adipocyte

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Adipose-derived stem cells represent a reliable adult stem cell source thanks to their abundance, straightforward isolation, and broad differentiation abilities. Consequently, human adipose-derived stem cells (hASCs) have been used in vitro for several innovative cellular therapy and regenerative medicine applications. However, the translation of a novel technology from the laboratory to the clinic requires first to evaluate its safety, feasibility, and potential efficacy through preclinical studies in animals. The anatomy and physiology of pigs and humans are very similar, establishing pigs as an attractive and popular large animal model for preclinical studies. Knowledge of the properties of porcine adipose-derived stem cells (pASCs) used in preclinical studies is critical for their success. While hASCs have been extensively studied this past decade, only a handful of reports relate to pASCs. The aim of this concise review is to summarize the current findings about the isolation of pASCs, their culture, proliferation, and immunophenotype. The differentiation abilities of pASCs and their applications in porcine preclinical models will also be reported.

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Section: Applications In Preclinical Modelsmentioning

confidence: 99%

Properties of porcine adipose-derived stem cells and their applications in preclinical models

Arrizabalaga

Nollert

2017

Adipocyte

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“…MSCs are known to be one source of TGF-β1 [ 14 – 15 ], but whether TGF-β1 secreted by MSCs exhibit potent immunosuppressive activity remains unknown. To address this issue, we isolated MSCs from WT or TGF-β1 +/− mice.…”

Section: Resultsmentioning

confidence: 99%

Mesenchymal stem cells inhibit T cell activation by releasing TGF-β1 from TGF-β1/GARP complex

et al. 2017

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Intervention with mesenchymal stem cells (MSCs) reveals a promising therapeutic tool to treat transplantation and autoimmune disease due to their immunoregulation capability. But the mechanisms of action are not fully investigated yet. Transforming growth factor-β1 (TGF-β1) exhibit multiple effects in migration, differentiation, and immunomodulation of MSCs. Glycoprotein A repetitions predominant (GARP) is an important marker of activated Treg (regulatory T cells). GARP binds latent TGF-β1 to regulate its activation, which is the indispensable step in Treg suppressing effector T cells. So far we don’t know whether GARP present on MSCs and its association with MSCs function. Our study show that MSCs express GARP which binds latent TGF-β1 on their cell surface. We also found that TGF-β1+/− MSCs produce less TGF-β1 and exhibit reduced capacity in inhibiting T cells. When TGF-β1 signaling pathway was blocked, MSCs show decreased activity in inhibiting T cells.Importantly, silencing GARP expression distinctively damaged the capacity of MSCs to inhibit IFN-γ production. These findings indicated the expression of GARP on MSCs and its functionality in activating LAP, thus demonstrating GARP as a novel biomarker and new target to improve the therapeutic efficacy of MSCs.

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“…The cardiac regenerative capacity of MSCs has been explored in several small 81,[123][124][125] and large animal 32,126-134 models of heart disease, including acute and chronic ischemic cardiomyopathies. Autologous, 127,129 allogeneic, 32,82,128 or xenogeneic 135,136 MSCs have been studied, using different routes of administration, including intracoronary, 129,[131][132][133][134]137 transendocardial, 32,128,135 systemic, 124 and intravenous. 43,125,132 Most of these approaches support that MSC therapy, regardless of source, is effective at reducing scar size and improving left ventricular ejection fraction (LVEF).…”

Section: Mscs For Cardiac Repair Preclinical Studiesmentioning

confidence: 99%

“…Autologous, 127,129 allogeneic, 32,82,128 or xenogeneic 135,136 MSCs have been studied, using different routes of administration, including intracoronary, 129,[131][132][133][134]137 transendocardial, 32,128,135 systemic, 124 and intravenous. 43,125,132 Most of these approaches support that MSC therapy, regardless of source, is effective at reducing scar size and improving left ventricular ejection fraction (LVEF). Specifically, a meta-analysis of 52 preclinical animal studies of cell therapy for ischemic heart disease 138 suggested that MSC therapy is safe and associated with moderate ($7.5%) but significant improvements in LVEF.…”

Section: Mscs For Cardiac Repair Preclinical Studiesmentioning

confidence: 99%

“…Animals treated with BM-MSCs also exhibited a better outcome compared to those treated with mononuclear cells. 138 While BM-MSCs have been most frequently utilized as a treatment of diseased hearts in a large animal model, 32,41,48,139,140 other sources, such as obtained from adipose tissue [132][133][134] and umbilical cord blood, 131 have also produced significant improvement in LV function, perfusion, and remodeling in a large animal model of MI.…”

Section: Mscs For Cardiac Repair Preclinical Studiesmentioning

confidence: 99%

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Mesenchymal Stem Cell-Based Therapy for Cardiovascular Disease: Progress and Challenges

et al. 2018

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Administration of mesenchymal stem cells (MSCs) to diseased hearts improves cardiac function and reduces scar size. These effects occur via the stimulation of endogenous repair mechanisms, including regulation of immune responses, tissue perfusion, inhibition of fibrosis, and proliferation of resident cardiac cells, although rare events of transdifferentiation into cardiomyocytes and vascular components are also described in animal models. While these improvements demonstrate the potential of stem cell therapy, the goal of full cardiac recovery has yet to be realized in either preclinical or clinical studies. To reach this goal, novel cell-based therapeutic approaches are needed. Ongoing studies include cell combinations, incorporation of MSCs into biomaterials, or pre-conditioning or genetic manipulation of MSCs to boost their release of paracrine factors, such as exosomes, growth factors, microRNAs, etc. All of these approaches can augment therapeutic efficacy. Further study of the optimal route of administration, the correct dose, the best cell population(s), and timing for treatment are parameters that still need to be addressed in order to achieve the goal of complete cardiac regeneration. Despite significant progress, many challenges remain.

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Allogenic adipose-derived stem cell therapy overcomes ischemia-induced microvessel rarefaction in the myocardium: systems biology study

Cited by 24 publications

References 51 publications

Properties of porcine adipose-derived stem cells and their applications in preclinical models

Properties of porcine adipose-derived stem cells and their applications in preclinical models

Mesenchymal stem cells inhibit T cell activation by releasing TGF-β1 from TGF-β1/GARP complex

Mesenchymal Stem Cell-Based Therapy for Cardiovascular Disease: Progress and Challenges

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