Decellularized Aortic Scaffold Alleviates H₂O₂-Induced Inflammation and Apoptosis in CD34+ Progenitor Cells While Driving Neovasculogenesis

Abstract

Bone marrow-derived stem/progenitor cells have been utilized for cardiac or vascular repair after ischemic injury, but they are subject to apoptosis and immune rejection in the ischemic site. Multiple scaffolds were used as delivery tools to transplant stem/ progenitor cells; however, these scaffolds did not show intrinsically antiapoptotic or anti-inflammatory properties. Decellularized aortic scaffolds that facilitate cell delivery and tissue repair were prepared by removing cells of patient-derived aortic tissues. Scanning electron microscopy (SEM) showed cells attached well to the scaffold after culturing for 5 days. Live/dead staining showed most seeded cells survived at day 7 on a decellularized aortic scaffold. Ki67 staining demonstrated that decellularized aortic scaffold promoted proliferation of bone marrow-derived CD34+ progenitor cells. Apoptosis of CD34+ progenitor cells induced by H 2 O 2 at high concentration was significantly alleviated in the presence of decellularized aortic scaffolds, demonstrating a protective effect against oxidative stress-induced apoptosis. Furthermore, decellularized aortic scaffolds significantly reduced the expression of proinflammatory cytokines (IL-8, GM-CSF, MIP-1β, GRO-α, Entoxin, and GRO) concurrently with an increase in anti-inflammatory cytokines (IL-2 and TGF-β) released from CD34+ progenitor cells when exposed to H 2 O 2 at low concentration. Finally, neovascularization was observed by H&E and immunohistochemical staining 14 days after the decellularized aortic scaffolds were subcutaneously implanted in nude mice. is preclinical study demonstrates that the use of a decellularized aortic scaffold possessing antiapoptotic and anti-inflammatory properties may represent a promising strategy for cardiovascular repair after ischemic injury.

Effect of cyclic mechanical loading on immunoinflammatory microenvironment in biofabricating hydroxyapatite scaffold for bone regeneration

“…On the other hand, some chemokines (GROα, PF4, NAP2, and RANTES) are considered to be important components of proinflammatory mediators and to interfere with the process of tissue regeneration [ [47] , [48] , [49] ]. As shown in Fig.…”

Peroxiredoxin-5 Knockdown Accelerates Pressure Overload-Induced Cardiac Hypertrophy in Mice

“…Apoptosis is known to contribute to various cardiovascular diseases, including heart failure, myocardial infarct, and reperfusion injury [ 35 , 36 ]. Previous research has also shown that cardiac hypertrophy is related to a reduced cell number due to enhanced apoptosis [ 37 , 38 ].…”

Biomedical Application of Decellularized Scaffolds

“…Then the extracellular scaffolds inoculated with bone marrow progenitor cells were placed in different concentrations of hydrogen peroxide and found to have good antiapoptotic properties. 213 Walawalkar et al used chemicals and enzymes to decellularize the bovine aorta. The results showed that compared with other scaffolds, large diameter aortic ECM scaffolds could not only be prepared but also reendothelialized.…”

“…Gao et al successfully prepared a decellularized aortic stent, which was used as the delivery carrier of bone marrow progenitor cells. Then the extracellular scaffolds inoculated with bone marrow progenitor cells were placed in different concentrations of hydrogen peroxide and found to have good antiapoptotic properties . Walawalkar et al used chemicals and enzymes to decellularize the bovine aorta.…”