BACKGROUND:Mesenchymal stem cells (MSCs) may serve as immunoregulators by producing various anti-inflammatory molecules. Under sufficient level of TNF-α, MSCs become activated and adopt immune-suppressive phenotype (MSCs type-2) by releasing various anti-inflammatory molecule including TGF-β and IL-10. However, the ability of MSC itself to produce IL-10 under TNF-α stimulation and the correlation of TGF-β production of MSCs to IL-10 level remains to be elucidated.AIM:In this study, MSCs were activated with various TNF-α doses to determine the increase of IL-10 and TGF-β level as well as its correlation.MATERIAL AND METHODS:This study used post-test only control group design, by using 3 study groups, consist of 1 control (C) and 2 treatments (T) (TNF-α = 5 and 10 ng/mL) with triplicate induced in MSC for 24 hours, then the levels of IL-10 and TGF-β were measured by using ELISA assay.RESULTS:The results of this study showed a significant increase of TGF-β and IL-10 levels (p < 0.05) at TNF-α 5 and 10 ng/mL dose of TNF-α. Moreover, there was a significant negative correlation between TGF-β and IL-10 level on 5 and 10 ng/mL dose TNF-α treatment.CONCLUSION:Based on our study, we conclude that the 5 ng/mL dose of TNF-α is a sufficient dose for MSCs to suppress the inflammatory milieu. The higher increase of TGF beta is due to the controlled inflammation by IL-10.

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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.

BACKGROUND: Acute renal failure (ARF) is a serious disease characterised by a rapid loss of renal functions due to nephrotoxic drug or ischemic insult. The clinical treatment approach such as dialysis techniques and continuous renal enhancement have grown rapidly during past decades. However, there is yet no significant effect in improving renal function. Hypoxia-preconditioned mesenchymal stem cells (HP-MSCs) have positive effects on the in vitro survival and stemness, in addition to angiogenic potential. AIM: In this study, we aimed to analyse the effect of HP-MSCs administration in improving renal function, characterised by blood urea nitrogen (BUN) and creatinine level. METHODS: A group of 15 male Wistar rats weighing 250 g to 300 g were used in this study (n = 5 for each group). Rats were randomly distributed into 3 groups: Vehicle control (Veh) as a control group, HP-MSCs and normoxia MSCs (N-MSCs) as the treatment group. Renal function was evaluated based on the BUN and creatinine levels using the colourimetric method on day 5 and 13. The histological analysis using HE staining was performed on day 13. RESULTS: The result showed there is a significant decrease in BUN and creatinine level (p < 0.05). The histological analysis of renal tissue also showed a significant decrease between Veh and treatment group (p < 0.05). CONCLUSION: Based on this study, we conclude that HP-MSCs have a superior beneficial effect than N-MSCs in improving renal function in an animal model of gentamicin-induced ARF.

Introduction: Immunomodulation properties of mesenchymal stem cells have attracted tremendous attention that eventually could regress liver fibrosis process. Aim: The study aims to demonstrate the immunomodulation activities of Umbilical cord-derived Mesenchymal stem cells (UC-MSCs) affecting interleukin-10 (IL-10) and hyaluronic acid (HA) secretion post intraperitoneal injection of CCl 4 , potent hepatotoxin, induced liver fibrosis among experimental rats. Methods: There were 18 Sprague-Dawley (SD) rats divided into three treatment groups (G1 sham group, G2 untreated liver fibrosis group, and G3 UC-MSCs treated-group) and isolated in Stem Cell and Cancer Research Facility, Semarang, Indonesia. Blood examination was conducted after 3 and 14 days of UC-MSCs transplantation using sandwich based ELISA followed by the histopathological analysis of rat liver tissue. ANOVA and posthoc LSD tests were determined the significance against all groups based on their quantitative measurement. Results: UC-MSCs have been successfully extracted and isolated as well as positive with osteogenic differentiation (Alizarin dye). In further analysis, there were significant mean differences among all groups through the ANOVA test, both IL-10 and HA secretion, concurrent with low-grade liver fibrosis in G3. IL-10 elevates during the early phase of UC-MSCs transplantation, and HA significantly reduced on the 14th day of transplantation, it characterizes the liver fibrosis that has been attenuated. Conclusion: The transplantation of UC-MSCs has given an opportunity for the treatment of a wide range of chronic liver diseases through the immunomodulation properties via its paracrine effects that regulate specific cytokine to suppress fibrosis development.

Background<br />Wounds are areas of physical or thermal damage of the epithelial layer of skin or mucosa. The wound healing process consists of hemostasis, inflammation, proliferation, and remodeling. Mesenchymal stem cells (MSCs) play a role in wound healing by suppressing potent pro-inflammatory molecules, such as tumor necrosis factor-<strong>α</strong> (TNF-<strong>α</strong>), leading to macrophage polarization from the pro-inflammatory type to the pro-regeneration type characterized by increasing vascular endothelial growth factor (VEGF) production. MSCs are able to increase VEGF level in-vivo correlated with collagen synthesis. The objective of this study was to assess the role of TNF-<strong>α</strong>-activated MSCs on VEGF in rat wounds. <br /><br />Methods<br />An experimental animal study with post-test only control group design was performed involving 24 Wistar rats. The rats were randomized into four groups  consisting of one control (K) and three treatment groups (P) (activated MSCs at doses of 3x105, 6x105, and 12x105 cells, respectively). The measurement of VEGF levels was done using ELISA assay while the collagen analysis was performed by light microscopy. One way ANOVA and Post Hoc LSD were used to analyze the data.<br /><br />Results<br />The results showed a significant increase in VEGF levels (p &lt;0.05) on day 3 and then a significant decrease on day 5 along with a significant increase in the amount of collagen on day 7 (p&lt;0.05).<br /><br />Conclusion<br />This study demonstrated that TNF-<strong>α</strong>-activated MSCs were able to regulate VEGF levels and collagen synthesis in wound healing in rats. The molecular mechanism by which TNF-<strong>α</strong>-activated MSCs stimulate cutaneous wound healing should be clarified further.

Background: The mechanisms underlying peripheral disorders during systemic lupus erythematosus (SLE) were found to be shared with tolerance disorders and mediated by T-regulator (T-reg) cells. Mesenchymal stem cells (MSCs) may inhibit T-cell subset differentiation and induce the T-reg cell phenotype. However, the capacity of MSCs to promote functional T-reg cells in SLE patients remains unclear. Objectives: This study aimed to analyze the capacity of MSCs to induce the production of functional CD4+ CD25+ Foxp3+ T-reg cells, in vitro, under co-culture conditions with human SLE cells. Methods: This study used a pre- and post-test control group design. Peripheral blood mononuclear cells (PBMCs) were extracted from SLE patients at the Kariadi Hospital, and MSCs were derived from human umbilical cords (hUCs) The PBMC control group was treated with standard medium, and the treatment group was co-cultured with hUC-MSCs. After 24 hours of co-culture incubation, T-reg cells were removed from the PBMC pool, using magnetic-activated cell sorting (MACS), and the population was assessed using the trypan blue exclusion assay. Results: A significant increase in the population of T-reg cells was observed (P < 0.001) after 24 hours of co-culture incubation with hUC-MSCs. Conclusion: This study concluded that MSCs have the capacity to enhance the T-reg population in human SLE PBMCs. Bangladesh Journal of Medical Science Vol.19(4) 2020 p.743-748

Background: Mesenchymal stem cells (MSCs) migrate and transmigrate to acute liver failure (ALF) area due to vascular endothelial growth factor (VEGF) stimulation as an attractant molecule then actively giving the paracrine signaling and or differentiating into primary hepatocytes, however the best route of MSCs transplanted to liver injury area remains unclear. &nbsp; Aim: In this study we compare intravenous (IV) and intraperitoneal (IP) route of MSCs administration by analyzing serum glutamic pyruvic transaminase (SGPT), serum glutamic-oxaloacetic transaminase (SGOT) and bilirubin level as improvement markers of liver function and VEGF as attractant-proliferation molecule on days 2 and 5. &nbsp; Materials and methods: Eighteen male Sprague-Dawley rats weighting 200 g were used in this study. They were divided in three study groups: vehicle control, IP and IV groups. The IV group was treated by MSCs at dose 1&times;106 by lateral tail vein injection and IP group received 1&times;106 MSCs via IP injection. The level of SGPT, SGOT and bilirubin were measured by an automatic analyzer, the VEGF level using enzyme-linked immunosorbent assay (ELISA), while the CD73 expression was evaluated using immunohistochemistry. &nbsp; Results: This study showed that IV injection of MSCs was more efficient for increasing liver function than IP treatment group that confirmed by the observed significant decrease in SGPT, SGOT and bilirubin level on days 2 and 5 (p<0.001). This effect was most likely mediated by the significant increase of VEGF level (p<0.05) on days 2 and 5. &nbsp; Conclusion: Our result conclude that an IV administration of MSCs was more efficacious than the IP administration for liver injury &nbsp;regeneration.&nbsp;