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Hypoxia-Mesenchymal Stem Cells Inhibit Intra-Peritoneal Adhesions Formation by Upregulation of the IL-10 Expression.

ABSTRACT: BACKGROUND:Intra-peritoneal adhesions (IPAs) common occurre in post abdominal surgical. Athough many methods have been developed for controlling IPAs, including mesenchymal stem cells (MSCs) application, however, there is none completely preventing in due to the mesothelial structure may promote the prolonged inflammations leading. Nevertheless hypoxia-MSCs (H-MSCs) have more potent in controlling the inflammation than normoxia-MSCs (N-MSCs) by releasing several anti-inflamation particularly IL-10, however the H-MSCs application to inhibit IPAs remain unclear. AIM:The aim of this study was to investigate the effectiveness of H-MSCs in preventing the AIPs event by releasing IL-10 on the ileum abrasion sutured omental patch as the animal model of peritoneal adhesion. METHODS:Using 24 IPAs animal model were randomly divided into 4 groups: Sham (Sh), Control (C), H-MSCs at high dose (T1) and H-MSCs at low dose (T2). H-MSCs were incubated under hypoxic conditions (5% O2), 37°C and 5% CO2 for 24 hours. The expression level of IL-10 was performed using RT-PCR analysis. The macroscopic appearance of IPAs was evaluated using Nair's scale base on the absence/presence of adhesion, whereas the microscopic by Zuhlke's scale at Hematoxylin and eosin (H&E) staining. RESULTS:This study showed a significanly increase in IL-10 expression (p < 0.05) at all T groups. In line with this, we also found a significant difference in IPAs between T groups and Control as well as a Sham (p < 0.05) either in the macroscopic or microscopic analysis. CONCLUSION:H-MSCs has a robust ability in inhibiting severe IPAs characterized by the decreased of adhesion formation and the enhanced expression of IL-10.

SUBMITTER: Muhar AM

PROVIDER: S-EPMC7061407 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Hypoxia-Mesenchymal Stem Cells Inhibit Intra-Peritoneal Adhesions Formation by Upregulation of the IL-10 Expression.

Muhar Adi Muradi AM Putra Agung A Warli Syah Mirsya SM Munir Delfitri D

Open access Macedonian journal of medical sciences 20191211 23

<h4>Background</h4>Intra-peritoneal adhesions (IPAs) common occurre in post abdominal surgical. Athough many methods have been developed for controlling IPAs, including mesenchymal stem cells (MSCs) application, however, there is none completely preventing in due to the mesothelial structure may promote the prolonged inflammations leading. Nevertheless hypoxia-MSCs (H-MSCs) have more potent in controlling the inflammation than normoxia-MSCs (N-MSCs) by releasing several anti-inflamation particul ...[more]

PMID: 32165932

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Project description:BackgroundAdhesion formation contributes to postoperative complications in abdominal and gynaecological surgery. Thus far, the prevention and treatment strategies have focused on mechanical barriers in solid and liquid form, but these methods are not in routine use. As autologous fat grafting has become popular in treatment of hypertrophic scars because of its immunomodulatory effects, we postulated that fat grafting could also prevent peritoneal adhesion through similar mechanisms.MethodsThis was a control versus intervention study to evaluate the effect of fat grafting in the prevention on peritoneal adhesion formation. An experimental mouse model for moderate and extensive peritoneal adhesions was used (n = 4-6 mice/group). Adhesions were induced mechanically, and a free epididymal fat graft from wild type or CAG-DsRed mice was injected preperitoneally immediately after adhesion induction. PET/CT imaging and scaling of the adhesions were performed, and samples were taken for further analysis at 7 and 30 days postoperation. Macrophage phenotyping was further performed from peritoneal lavage samples, and the expression of inflammatory cytokines and mesothelial layer recovery were analysed from peritoneal tissue samples.ResultsFat grafting significantly inhibited the formation of adhesions. PET/CT results did not show prolonged inflammation in any of the groups. While the expression of anti-inflammatory and anti-fibrotic IL-10 was significantly increased in the peritoneum of the fat graft-treated group at 7 days, tissue-resident and repairing M2 macrophages could no longer be detected in the fat graft at this time point. The percentage of the continuous, healed peritoneum as shown by Keratin 8 staining was greater in the fat graft-treated group after 7 days.ConclusionsFat grafting can inhibit the formation of peritoneal adhesions in mice. Our results suggest that fat grafting promotes the peritoneal healing process in a paracrine manner thereby enabling rapid regeneration of the peritoneal mesothelial cell layer.

Project description:PurposeFibrin clot is essential for post-operative abdominal adhesion formation. Fucoidans, sulfated polysaccharides, inhibit fibrin clot formation. In addition, they inhibit inflammation and fibrosis, which also play important roles in adhesion formation. The purpose of this study was to evaluate fucoidans' potential for inhibiting post-operative abdominal adhesions and measure their effects on systemic coagulation parameters when administered intraperitoneally (IP).Methods and materialsFemale Sprague Dawley rats were studied. A 2.5x2.5cm full thickness segment of abdominal wall was excised. The skin edges were approximated. This model induces extensive adhesions and allows objective quantitation. Three fucoidans were evaluated- Sigma Fucoidan Crude (SFC), Fucus vesiculosis 95% (Sigma) and, Peridan. One protocol involved continuous infusion into the abdomen from a subcutaneous osmotic pump. Alternatively, boluses of the solutions were injected IP at the end of the operation. Rats were sacrificed a week later. Adhesion extent was scored. Systemic coagulation effects of fucoidans were also evaluated. INR and aPTT were measured following IP injection of the fucoidan solutions and after 7 days of continuous infusion.ResultsAnimals given a continuous infusion of either SFC or Peridan yielded adhesion reduction of 80 to 90% from control. Bolus Peridan had no discernable influence on adhesion formation, but a single bolus of SFC caused significant adhesion reductions. Peridan resulted in prompt aPTT elevations which fell to nearly normal by 5 hours. The maximum peak value after SFC injection was seen in 15 hours. The maximal INR elevations were around 2. Measurement of INR and aPTT after a week of continuous infusion of either Peridan or SFC, were always in the normal control range. The third agent, Sigma, frequently yielded intraperitoneal infection found at autopsy.ConclusionsThese findings indicate that selected fucoidans infused intraperitoneally for a week after abdominal operations reduce adhesion extent by up to 90%.

Project description:Joint trauma leads to post-traumatic inflammation with upregulation of inflammatory cytokines and degradative enzymes. If severe enough, this response can lead to irreversible post-traumatic osteoarthritis. Interleukin-10 (IL-10), a cytokine with potent anti-inflammatory effects, has been shown to have chondroprotective effects. A gene therapy approach using a vector to overexpress IL-10 in the joint represents a feasible method of delivering sustained high doses of IL-10 to post-traumatic joints. We hypothesized that an AAV5 vector overexpressing IL-10 would result in rapid and sustained IL-10 expression following direct intra-articular injection and that this increase would not be reflected in systemic circulation. In addition, we hypothesized that intra-articular AAV5-IL-10 injection would not induce a local inflammatory response. Twelve horses were assigned to either treatment (AAV5-IL-10-injected) or control (PBS-injected) groups. Middle carpal joints were injected with 1012 vector genomes/joint or phosphate-buffered saline (PBS) alone (3?mL). Serial synovial fluid samples were analyzed for inflammatory changes, IL-10 concentration, and vector genome copy number. Serum samples were also analyzed for IL-10 concentration and vector genome copy number. Synovial membrane was collected on day 84. Synovial fluid IL-10 was significantly increased within 48?h of AAV5-IL-10 injection and remained increased, compared to PBS-injected joints, until day 84. Serum IL-10 was not different between groups. Vector administration did not cause a significant synovial inflammatory response. Vector genomes were detectable in the plasma, synovial fluid, and synovial membrane of AAV5-IL-10-injected horses only. IL-10 has the potential to modulate the articular inflammatory response, thereby protecting cartilage from degradation and osteoarthritis. This study demonstrates the feasibility and efficiency of intra-articular AAV5-IL-10, and future studies investigating the chondroprotective effects of IL-10 in inflamed joints in vivo are warranted.

Dataset Information

Hypoxia-Mesenchymal Stem Cells Inhibit Intra-Peritoneal Adhesions Formation by Upregulation of the IL-10 Expression.

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Hypoxia-Mesenchymal Stem Cells Inhibit Intra-Peritoneal Adhesions Formation by Upregulation of the IL-10 Expression.

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