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

Abstract

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.

Icariside II Restores Vascular Smooth Muscle Cell Contractile Phenotype by Enhancing the Focal Adhesion Signaling Pathway in the Rat Vascular Remodeling Model

“…IHC experiments were implemented for assessing the protein expression level of the VSMC synthetic marker OPN in vitro . Protocols for the IHC experiments were described previously ( Wen et al, 2020 ). In brief, after de-paraffinization and rehydration, sections were incubated with 3% H 2 O 2 to deactivate endogenous peroxidase followed by a heat-induced antigen retrieval process.…”

Stem Cell Based Approaches to Modulate the Matrix Milieu in Vascular Disorders

“…Wen et al also showed I.V. administration of Umbilical Cord MSCs (UC-MSCs) was effective in attenuating aneurysmal expansion, reducing elastin degradation and fragmentation, inhibiting MMPs and TNFα expression, and to promote contractile phenotype of SMCs in the AAA wall of elastase-induced rat model ( 100 ).…”

“…Overall, MSC therapy was effective in reducing inflammation and ECM degradation at the AAA wall site, through the secretion of several anti-inflammatory cytokines, protease inhibitors and ECM synthesis stimulators ( 97 – 100 ). MSC treatment was also effective in regressing the growth of already-formed AAAs ( 97 , 98 , 102 , 113 ).…”

Eicosapentaenoic acid is associated with the attenuation of dysfunctions of mesenchymal stem cells in the abdominal aortic aneurysm wall

“…25 Recent studies have reported that MSC-based cellular therapy can effectively attenuate AAA progression. 26,27 Aortic MSCs from patients with AAA have significantly increased MMP-9 expression and activity compared with healthy MSCs. 19 EPA-stimulated MSCs enhance the secretion of anti-inflammatory factors such as resolvin and prostaglandins.…”