Adipose-Derived Stem Cell Transplantation Attenuates Inflammation and Promotes Liver Regeneration after Ischemia-Reperfusion and Hemihepatectomy in Swine

Abstract

Aim To study the anti-inflammatory and liver regenerative effects of adipose-derived mesenchymal stem cells (ADSCs) on a porcine model of ischemia-reperfusion (IR) and hemihepatectomy. Methods Eighteen healthy Bama miniature pigs were randomly divided into the sham-operated (sham), untreated IR injury (IRI), and ADSC-transplanted (ADSC) groups. Hepatic IR was established by laparoscopic hemihepatectomy. ADSCs were transplanted directly into the liver parenchyma after the surgery. Hepatic inflammation and liver regeneration were evaluated by histopathological examination and assessment of relevant cytokines and other factors. Results ADSC transplantation successfully ameliorated the IRI-induced histopathological damage and the high levels of pro-inflammatory cytokines like IL-1β, IL-6, and TNF-α. In addition, the ADSCs enhanced the expression of the anti-inflammatory IL-10, regenerative factors including HGF, Cyclin D1, and proliferating cell nuclear antigen (PCNA), and angiogenic factors like VEGF, ANG-1, and ANG-2. Conclusions ADSCs attenuated the hepatic IRI-induced inflammatory response and promoted liver regeneration.

Adipose-Derived Stem Cells Protect Ischemia-Reperfusion and Partial Hepatectomy by Attenuating Endoplasmic Reticulum Stress

“…The Mesenchymal and Tissue Stem Cell Committee of the International Cell Therapy Association has proposed a minimum defined standard for characterizing human MSCs (Pittenger et al, 1999;Dominici et al, 2006), including adhesion to plastic, multi-directional differentiation ability and expression of distinct surface markers. The ADSCs extracted from the subcutaneous fat of pigs differentiate into osteogenic, adipogenic and hepatic cells, and express CD44, CD29, and CD90 but not CD34 (Brückner et al, 2013;Jiao et al, 2019). Based on these criteria, we successfully isolated and expanded porcine ADSCs in vitro.…”

Adipose-Derived Stem Cells: Current Applications and Future Directions in the Regeneration of Multiple Tissues

“…Additionally, ADSC treatment led to a marked decline in the levels of adverse hematological indicators, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T-BIL), and lactate dehydrogenase (LDH). A different study reported that ADSCs suppressed the level of inflammatory cytokines such as IL-1 β , IL-6, and TNF, while enhancing the secretion of the anti-inflammatory factor IL-10 and the regenerative factors HGF and cyclin D1, thereby ameliorating the IRI-induced damage [ 152 ]. Similar hepatoprotective effects were also found in other trials [ 153 ].…”

Encapsulation of Adipose-Derived Mesenchymal Stem Cells in Calcium Alginate Maintains Clonogenicity and Enhances their Secretory Profile

“…Furthermore, preclinical studies involving injection of ASCs into cardiac muscle in rats [ 53 , 54 ] and pig liver [ 55 ] reported no inflammatory reaction or fibrosis at the injection sites, and similar results were reported when ASCs were systemically injected: The cells were detectable in inflammatory tissues and appeared to play a role in reducing inflammation [ 56 , 57 ]. Nevertheless, in human medicine, it is very important to limit the risks of triggering an immune response.…”