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.
Highlights
The liver is the largest parenchymal organ in mammals, with functions including detoxification, glycogen storage, and synthesis of secretory proteins
adipose-derived mesenchymal stem cells (ADSCs) isolated from the porcine adipose tissue adhered to the plastic dishes within 24 h of culture and exhibited the typical spindle shape after 2-3 days (Figure 2(a))
Multipotent ADSCs were successfully enriched from porcine adipose tissue
Summary
The liver is the largest parenchymal organ in mammals, with functions including detoxification, glycogen storage, and synthesis of secretory proteins. The first hepatectomies were performed in 1949 by Ichio Honjo (Kyoto University) [1] and in 1952 by Jean-Louis Lortat-Jacob [2]. Laparoscopic liver resection was first performed in the 1990s [3, 4]. It minimizes damage to the abdominal wall nerves and muscles; reduces blood loss, pain, and postoperative adhesion; and accelerates recovery [5]. Small-for-size syndrome [6] after large area hepatectomy and partial liver transplantation will lead to postoperative liver failure. The most effective treatment for terminal liver failure is orthotopic liver transplantation (OLT), which is limited due to organ shortage, immune rejection, high costs, and posttransplantation complications. There is an urgent need to devise novel strategies to repair liver damage and promote liver regeneration
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