Study the effects of mesenchymal stem cell conditioned medium injection in mouse model of acute colitis

Pouya, Sedigheh; Heidari, Maryam; Baghaei, Kaveh; Aghdaei, Hamid Asadzadeh; Moradi, Abdolvahab; Namaki, Saeed; Zali, Mohammad Reza; Hashemi, Seyed Mahmoud

doi:10.1016/j.intimp.2017.11.001

Cited by 51 publications

(46 citation statements)

References 31 publications

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“…We have been able to confirm the therapeutic effect of naive hUCB‐MSCs in colitis induced by 3% DSS, and it has been reported that 2.5–3% DSS is mainly used to induce colitis. (Nikolic et al, ; Pouya et al, ). We have tested 3%, 4%, and 5% DSS to induce colitis and confirmed severe symptoms by observing shorted colon lengths in the 4% and 5% DSS treated groups (Figure S2).…”

Section: Discussionmentioning

confidence: 99%

Preconditioning with interleukin‐1 beta and interferon‐gamma enhances the efficacy of human umbilical cord blood‐derived mesenchymal stem cells‐based therapy via enhancing prostaglandin E2 secretion and indoleamine 2,3‐dioxygenase activity in dextran sulfate sodium‐induced colitis

Yoo

Park

et al. 2019

J Tissue Eng Regen Med

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Preconditioning with inflammatory cytokines has improved mesenchymal stem cells characteristics, including differentiation and immunomodulating functions. In this study, we developed a preconditioning combination strategy using interleukin‐1beta (IL‐1β) and interferon‐gamma (IFN‐γ) to enhance the immuneregulatory ability of human umbilical cord blood‐derived mesenchymal stem cells (hUCB‐MSCs). Our results showed that hUCB‐MSCs preconditioned with IL‐1β and IFN‐γ (primed hUCB‐MSCs) created a statistically significant decrease in peripheral blood mononuclear cell proliferation, indicating that their immunosuppressive ability was increased. The secretion of PGE2, cyclooxygenase 2 mRNA expression, and indoleamine 2,3‐dioxygenase (IDO) mRNA expression in primed hUCB‐MSCs was significantly higher than those in the untreated hUCB‐MSCs or the IL‐1β or IFN‐γ only treated hUCB‐MSCs. When inhibitors of IDO and PGE2 were treated, peripheral blood mononuclear cell proliferation, which is inhibited by primed hUCB‐MSCs, was recovered. We found that Th1 T cell differentiation was also inhibited by PGE2 and IDO in the primed hUCB‐MSCs, and Tregs differentiation was increased by PGE2 and IDO in the primed hUCB‐MSCs. Furthermore, the primed hUCB‐MSCs as well as supernatants increase CD4+ T cells migration. We demonstrated the therapeutic effects of primed hUCB‐MSCs in dextran sulfate sodium‐induced colitis model. In conclusion, we have demonstrated that primed hUCB‐MSCs simultaneously enhance PGE2 and IDO and greatly improve the immunoregulatory capacity of MSCs, and we have developed an optimal condition for pretreatment of MSCs for the treatment of immune diseases. Our results raise the possibility that the combination of PGE2 and IDO could be therapeutic mediators for controlling immunosuppression of MSCs.

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Section: Discussionmentioning

confidence: 99%

Preconditioning with interleukin‐1 beta and interferon‐gamma enhances the efficacy of human umbilical cord blood‐derived mesenchymal stem cells‐based therapy via enhancing prostaglandin E2 secretion and indoleamine 2,3‐dioxygenase activity in dextran sulfate sodium‐induced colitis

Yoo

Park

et al. 2019

J Tissue Eng Regen Med

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“…In application, a therapeutic efficacy assessment of MSCs by Ahmed and colleagues indicates that genetic expressions of markers of inflammation (IL-23, IFN-γ, TNF-α, and ICAM-1) within the intestinal mucosa of MSC-treated mice appreciably lowered, resulting in a significant improvement in weight gain, stool condition, and normal histopathology of tissues analyzed [86]. In another work, the amount of Treg Stem Cells International cells and the expression of TGF-β and IL-10 were upregulated while IL-17 levels rather decreased when MSCconditioned medium was administered [87]. The outcome was inhibited loss of weight and bleeding, enhanced consistency of feces, and improved disease activity index (DAI), as well as decreased colon inflammation and mucosal degeneration.…”

Section: Therapeutic Utility Of Msc In Experimental Ibdmentioning

confidence: 99%

The Achievements and Challenges of Mesenchymal Stem Cell-Based Therapy in Inflammatory Bowel Disease and Its Associated Colorectal Cancer

Ocansey

Qiu

Wang

et al. 2020

Stem Cells International

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Approximately 18.1×106 new cases of cancer were recorded globally in 2018, out of which 9.6 million died. It is known that people who have Inflammatory Bowel Disease (IBD) turn to be prone to increased risks of developing colorectal cancer (CRC), which has global incident and mortality rates of 10.2% and 9.2%, respectively. Over the years, conventional treatments of IBD and its associated CRC have been noted to provide scarce desired results and often with severe complications. The introduction of biological agents as a better therapeutic approach has witnessed a great deal of success in both experimental and clinical models. With regard to mesenchymal stem cell (MSC) therapy, the ability of these cells to actively proliferate, undergo plastic differentiation, trigger strong immune regulation, exhibit low immunogenicity, and express abundant trophic factors has ensured their success in regenerative medicine and immune intervention therapies. Notwithstanding, MSC-based therapy is still confronted with some challenges including the likelihood of promoting tumor growth and metastasis, and possible overestimated therapeutic potentials. We review the success story of MSC-based therapy in IBD and its associated CRC as documented in experimental models and clinical trials, examining some of the challenges encountered and possible ways forward to producing an optimum MSC therapeutic imparts.

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“…Conditioned medium preparation protocol has been reported in several previous studies. 17,22,36 Briefly, AD-MSCs at second passage with 70%-80% confluency were incubated in serum-free DMEM/F12 media under standard and hypoxic conditions. After 48 hours, the CM of AD-MSCs and HP-MSCs was collected.…”

Section: Preparation and Total Protein Assay Of CM And Hcmmentioning

confidence: 99%

“…24,25 Some studies reported the anti-inflammatory and regenerative effects of MSCderived CM. 17,22,36 Proteomics analysis of MSC-CM showed several cytokines, chemokines and growth factors with anti-inflammatory, anti-apoptotic, anti-fibrotic and regenerative properties. 28,31 Therefore, it seems that CM, as a multi-functional drug, can be a suitable and simplified new approach for the treatment of AP.…”

Section: Effect Of CM and Hcm On Serum Amylase And Lipase Levelsmentioning

confidence: 99%

Effect of Hypoxia Preconditioned Adipose-Derived Mesenchymal Stem Cell Conditioned Medium on Cerulein-Induced Acute Pancreatitis in Mice

et al. 2020

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Purpose: Acute pancreatitis (AP) is an inflammatory disorder distinguished by tissue injury and inflammation of the pancreas. Using paracrine potential of mesenchymal stem cells (MSCs) provides a useful clinical approach in treating inflammatory diseases. We investigated the therapeutic effects of adipose-derived MSC conditioned medium (CM) and hypoxia preconditioned adipose-derived MSC conditioned medium (HCM) in cerulein-induced AP in mice. Methods: AP was induced in C57BL/6 mice by intraperitoneal injection of cerulein (75 μg/ kg/h × 7 times). One hour following the last injection of cerulein, mice were treated with intraperitoneal injection of CM and HCM (500 µL/mice/30 min × 3 times). Twelve hours following the treatment, serum levels of amylase and lipase were measured. In addition, pancreas pathological changes, immunohistochemical examinations for evaluation of IL-6 expression and pancreatic myeloperoxidase (MPO) enzyme activity were analyzed. Results: The in vitro results of the morphological, differentiation and immunophenotyping analyses confirmed that hypoxia preconditioned MSCs (HP-MSCs) conserve MSCs characteristics after preconditioning. However, HP-MSCs significantly expressed high mRNA level of hypoxia inducible factor 1-α and higher level of total protein. The in vivo findings of the current study showed that CM and HCM significantly reduced the amylase & lipase activity, the severity of pancreas tissue injury and the expression of IL-6 and MPO enzyme activity compared with the AP group. However, no significant difference between CM and HCM groups was demonstrated. Conclusion: Use of CM and HCM can attenuate cerulein-induced AP and decrease inflammation in the pancreas tissue in AP mice.

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Study the effects of mesenchymal stem cell conditioned medium injection in mouse model of acute colitis

Cited by 51 publications

References 31 publications

Preconditioning with interleukin‐1 beta and interferon‐gamma enhances the efficacy of human umbilical cord blood‐derived mesenchymal stem cells‐based therapy via enhancing prostaglandin E2 secretion and indoleamine 2,3‐dioxygenase activity in dextran sulfate sodium‐induced colitis

Preconditioning with interleukin‐1 beta and interferon‐gamma enhances the efficacy of human umbilical cord blood‐derived mesenchymal stem cells‐based therapy via enhancing prostaglandin E2 secretion and indoleamine 2,3‐dioxygenase activity in dextran sulfate sodium‐induced colitis

The Achievements and Challenges of Mesenchymal Stem Cell-Based Therapy in Inflammatory Bowel Disease and Its Associated Colorectal Cancer

Effect of Hypoxia Preconditioned Adipose-Derived Mesenchymal Stem Cell Conditioned Medium on Cerulein-Induced Acute Pancreatitis in Mice

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