Periadventitial Adipose-Derived Stem Cell Treatment Halts Elastase-Induced Abdominal Aortic Aneurysm Progression

Blose, Kory J.; Ennis, Terri L.; Arif, Batool; Weinbaum, Justin S.; Curci, John A.; Vorp, David A.

doi:10.2217/rme.14.61

Cited by 28 publications

(32 citation statements)

References 34 publications

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“…Likely, ASC‐secreted elastin contributed to this normalization, but ASC might also inhibit extracellular elastase. This corroborates studies that postulate that normalization of the elastin integrity is of therapeutic benefit in AAA . The ASC‐loaded patches treated groups also showed that the density of medial SMC was preserved.…”

Section: Discussionsupporting

confidence: 89%

“…This is unlikely, because the presence of macrophages was more distal to the media, in particular in comparison to untreated AAAs and those treated with bare patches only. Other studies used intravenous or intramural delivery of stem cells which resulted in poor retention of stem cell . In a porcine model for aneurysm, GFP‐marked bone marrow‐derived were detectable at one week after their injection into the aorta .…”

Section: Discussionmentioning

confidence: 99%

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Perivascular scaffolds loaded with adipose tissue‐derived stromal cells attenuate development and progression of abdominal aortic aneurysm in rats

Parvizi

Petersen

Spreuwel-Goossens

et al. 2018

J Biomedical Materials Res

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Abdominal aortic aneurysm (AAA) is the pathological dilation and weakening of the abdominal aorta wall. Inflammation, degradation of the extracellular matrix (ECM) and loss of smooth muscle cells and skewing of their function are pivotal in AAA pathology. We developed a recombinant collagen-based patch (RCP) to provide structural integrity and deliver Adipose tissue-Derived Stromal Cells (ASC) for repair. Patches supported adhesion and function as well as proliferation of ASC. ASC-loaded RCPs or bare patches, applied around the aorta after AAA induction in rats, both maintained structural integrity of the aortic wall at time of explant (2w). However, wall thinning, accompanied by loss of elastin fibers and loss of medial SMC, was only attenuated in ASC-loaded RCP-treated AAA rats. Interestingly, this coincided with migration of ASC into the media and a reduced influx of macrophages. We hypothesize that the medially-migrated ASC dampened or skewed the adverse innate immunity and thus suppressed SMC apoptosis, phenotypic skewing and elastin degradation. We conclude that the periadventitial delivery of ASC with RCP suppresses development and progression of AAA, which is has an expected future clinical benefit in combination with an appropriate early screening program of patients at risk for aneurysms. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2494-2506, 2018.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Perivascular scaffolds loaded with adipose tissue‐derived stromal cells attenuate development and progression of abdominal aortic aneurysm in rats

Parvizi

Petersen

Spreuwel-Goossens

et al. 2018

J Biomedical Materials Res

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“…The AAA stem cells expressed macrophage surface antigens (CD68), but not VSMC (SM22) or fibroblast (FSP1) markers, and co localized in the aortic wall with the cellular marker of proliferation Ki67. In another study adipose-tissue-derived mesenchymal stem cells were delivered to the aortae of mice induced to have AAA with an elastase treatment [66]. The mice receiving stem cells had smaller AAAs and the elastin fragmentation was less pronounced.…”

Section: Pathophysiology Of Aaamentioning

confidence: 99%

Understanding the pathogenesis of abdominal aortic aneurysms

Kuivaniemi

Ryer

Elmore

et al. 2015

Expert Review of Cardiovascular Therapy

299

240

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Summary An aortic aneurysm is a dilatation in which the aortic diameter is ≥ 3.0 cm. If left untreated, the aortic wall continues to weaken and becomes unable to withstand the forces of the luminal blood pressure resulting in progressive dilatation and rupture, a catastrophic event associated with a mortality of 50 – 80%. Smoking and positive family history are important risk factors for the development of abdominal aortic aneurysms (AAA). Several genetic risk factors have also been identified. On the histological level, visible hallmarks of AAA pathogenesis include inflammation, smooth muscle cell apoptosis, extracellular matrix degradation, and oxidative stress. We expect that large genetic, genomic, epigenetic, proteomic and metabolomic studies will be undertaken by international consortia to identify additional risk factors and biomarkers, and to enhance our understanding of the pathobiology of AAA. Collaboration between different research groups will be important in overcoming the challenges to develop pharmacological treatments for AAA.

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“…Recently, preclinical studies have found mesenchymal stem cell (MSC)-based cellular therapy is beneficial to AAA initiation and progression [14][15][16][17][18][19][20][21]. Parvizi et al [20,21] demonstrated that perivascular scaffolds loaded with adipose-derived MSCs could attenuate AAA development, prevent loss of VSMCs, and decrease macrophage infiltration in rats.…”

Section: Introductionmentioning

confidence: 99%

Human Umbilical Cord Mesenchymal Stem Cells Attenuate Abdominal Aortic Aneurysm Progression in Sprague-Dawley Rats: Implication of Vascular Smooth Muscle Cell Phenotypic Modulation

Wen

Wang

Gong

et al. 2020

Stem Cells and Development

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Abdominal aortic aneurysm (AAA) is life-threatening, for which efficient nonsurgical treatment strategy has not been available so far. Several previous studies investigating the therapeutic effect of mesenchymal stem cells (MSCs) in AAA indicated that MSCs could inhibit aneurysmal inflammatory responses and extracellular matrix destruction, and suppress aneurysm occurrence and expansion. Vascular smooth muscle cell (VSMC) phenotypic plasticity is reported to be predisposed in AAA initiation and progression. However, little is known about the effect of MSCs on VSMC phenotypic modulation in AAA. In this study, we investigate the therapeutic efficacy of umbilical cord mesenchymal stem cells (UC-MSCs) in elastase-induced AAA model and evaluate the effect of UC-MSC on VSMC phenotypic regulation. We demonstrate that the intravenous injection of UC-MSC attenuates elastase-induced aneurysmal expansion, reduces elastin degradation and fragmentation, inhibits MMPs and TNFa expression, and preserves and/or restores VSMC contractile phenotype in AAA. Taken together, these results highlight the therapeutic and VSMC phenotypic modulation effects of UC-MSC in AAA progression, which further indicates the potential of applying UC-MSC as an alternative treatment candidate for AAA.

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Periadventitial Adipose-Derived Stem Cell Treatment Halts Elastase-Induced Abdominal Aortic Aneurysm Progression

Cited by 28 publications

References 34 publications

Perivascular scaffolds loaded with adipose tissue‐derived stromal cells attenuate development and progression of abdominal aortic aneurysm in rats

Perivascular scaffolds loaded with adipose tissue‐derived stromal cells attenuate development and progression of abdominal aortic aneurysm in rats

Understanding the pathogenesis of abdominal aortic aneurysms

Human Umbilical Cord Mesenchymal Stem Cells Attenuate Abdominal Aortic Aneurysm Progression in Sprague-Dawley Rats: Implication of Vascular Smooth Muscle Cell Phenotypic Modulation

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