Differential immunomodulation of human mesenchymal stromal cells from various sources in an inflammation mimetic milieu

Sundaram, Rajasundari Meenakshi; Nandabalan, Sangeetha Kadapakkam; Rupert, Secunda; Srinivasan, Prasanna; Sankar, Pavithra; Patra, Bamadeb; Verma, Rajneesh; Vennila, Rosy; Sathyanesan, Jeswanth; Surendran, Rajagopal

doi:10.1016/j.jcyt.2021.09.005

Cited by 4 publications

(3 citation statements)

References 41 publications

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“…The recent development of stem cell technology has revolutionized the treatment of various diseases and laid the foundation for immunomodulation 24 . To investigate WJ‐MSCs' function, we first cultured MSCs obtained from human umbilical cords 21 .…”

Section: Resultsmentioning

confidence: 99%

“…The recent development of stem cell technology has revolutionized the treatment of various diseases and laid the foundation for immunomodulation. 24 To investigate WJ-MSCs' function, we first cultured MSCs obtained from human umbilical cords. 21 Our results showed that a small number of WJ-MSCs appeared around the implanted blocks after seeding for 6-7 days (Figure 1a).…”

Section: Isolation Culture and Characterization Of Wj-mscsmentioning

confidence: 99%

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Human Wharton's jelly‐derived mesenchymal stem cells prevent pregnancy loss in a rat by JAK/STAT‐mediated immunomodulation

Ding

Jin

et al. 2023

J of Obstet and Gynaecol

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AimSpontaneous abortion (SA) is a multiple‐original syndrome with immune imbalance as one of its major risk factors. As Wharton's jelly‐mesenchymal stem cells (WJ‐MSCs) are considered to be able to prevent abortion, this study aims to explore the currently poorly understood underlining molecular signaling pathways and regulatory mechanisms of WJ‐MSCs in pregnancy maintenance.MethodsAbortion mode is established by subcutaneous injection of bromocriptine in rat on day 9 and abortion prevention is achieved by WJ‐MSCs injection via tail vein. WJ‐MSCs were cultured with/without the inhibitors of JAK/STAT or NF‐κB. The uterus was collected on the 14th day of gestation and the rate of embryo absorption was calculated. The expression of Th1/Th2/Th3 cytokines in decidual, placental tissue, and peripheral blood was analyzed.ResultsWJ‐MSCs treatment significantly reduced the abortion rate in bromocriptine‐treated pregnancy such that it was not significantly different from a normal pregnancy. JAK/STAT inhibition abolished pregnancy preserving effects of WJ‐MSCs but NF‐κB inhibition did not. The levels of Th1‐related cytokines and mRNA levels in the bromocriptine abortion model were significantly higher than the normal pregnancy group and ethanol control group, while levels of the Th2‐related cytokines and mRNA levels significantly decreased. WJ‐MSCs transfusion into the abortion model restored cytokine profiles such that they were not significantly different from the normal pregnancy group and ethanol control group. JAK/STAT inhibition of WJ‐MSCs prevented their effect on cytokine and mRNA levels, but NF‐κB inhibition did not.ConclusionsWJ‐MSCs significantly lower the rate of embryo resorption of spontaneous abortion by reducing Th1‐related cytokines while increasing Th2 and Th3‐related cytokines in JAK/STAT‐dependent manner.

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Section: Resultsmentioning

confidence: 99%

Section: Isolation Culture and Characterization Of Wj-mscsmentioning

confidence: 99%

Human Wharton's jelly‐derived mesenchymal stem cells prevent pregnancy loss in a rat by JAK/STAT‐mediated immunomodulation

Ding

Jin

et al. 2023

J of Obstet and Gynaecol

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“…Priming can induce an anti-inflammatory state in MSCs, causing them to secrete more bioactive molecules and improving their therapeutic effects[ 9 , 10 ]. Interferon (IFN)-γ-primed MSCs have been shown to have more stable and stronger abilities to regulate immune responses and prevent damage in many disease models[ 11 - 13 ].…”

Section: Introductionmentioning

confidence: 99%

Interferon-γ priming enhances the therapeutic effects of menstrual blood-derived stromal cells in a mouse liver ischemia-reperfusion model

Zhang,

Zhou,

et al. 2023

World J Stem Cells

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BACKGROUND Mesenchymal stem cells (MSCs) have been used in liver transplantation and have certain effects in alleviating liver ischemia-reperfusion injury (IRI) and regulating immune rejection. However, some studies have indicated that the effects of MSCs are not very significant. Therefore, approaches that enable MSCs to exert significant and stable therapeutic effects are worth further study. AIM To enhance the therapeutic potential of human menstrual blood-derived stromal cells (MenSCs) in the mouse liver ischemia-reperfusion (I/R) model via interferon-γ (IFN-γ) priming. METHODS Apoptosis was analyzed by flow cytometry to evaluate the safety of IFN-γ priming, and indoleamine 2,3-dioxygenase (IDO) levels were measured by quantitative real-time reverse transcription polymerase chain reaction, western blotting, and ELISA to evaluate the efficacy of IFN-γ priming. In vivo , the liver I/R model was established in male C57/BL mice, hematoxylin and eosin and TUNEL staining was performed and serum liver enzyme levels were measured to assess the degree of liver injury, and regulatory T cell (Treg) numbers in spleens were determined by flow cytometry to assess immune tolerance potential. Metabolomics analysis was conducted to elucidate the potential mechanism underlying the regulatory effects of primed MenSCs. In vitro , we established a hypoxia/reoxygenation (H/R) model and analyzed apoptosis by flow cytometry to investigate the mechanism through which primed MenSCs inhibit apoptosis. Transmission electron microscopy, western blotting, and immunofluorescence were used to analyze autophagy levels. RESULTS IFN-γ-primed MenSCs secreted higher levels of IDO, attenuated liver injury, and increased Treg numbers in the mouse spleens to greater degrees than untreated MenSCs. Metabolomics and autophagy analyses proved that primed MenSCs more strongly induced autophagy in the mouse livers. In the H/R model, autophagy inhibitors increased the level of H/R-induced apoptosis, indicating that autophagy exerted protective effects. In addition, primed MenSCs decreased the level of H/R-induced apoptosis via IDO and autophagy. Further rescue experiments proved that IDO enhanced the protective autophagy by inhibiting the mammalian target of rapamycin (mTOR) pathway and activating the AMPK pathway. CONCLUSION IFN-γ-primed MenSCs exerted better therapeutic effects in the liver I/R model by secreting higher IDO levels. MenSCs and IDO activated the AMPK-mTOR-autophagy axis to reduce IRI, and IDO increased Treg numbers in the spleen and enhanced the MenSC-mediated induction of immune tolerance. Our study suggests that IFN-γ-primed MenSCs may be a novel and superior MSC product for liver transplantation in the future.

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Human Wharton’s jelly-derived mesenchymal stem cells prevent pregnancy loss in a rat by JAK/STAT-mediated immunomodulation

Ding

Yang

et al. 2022

Preprint

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Spontaneous abortion (SA) is a syndrome with many origins. Among them, immune imbalance is a major risk factor for SA. Wharton's jelly-mesenchymal stem cells (WJ-MSCs) are considered to be able to prevent abortion. However, the underlining molecular signaling pathways and regulatory mechanisms of WJ-MSCs in pregnancy maintenance are poorly understood. Here abortion mode is established by subcutaneous injection of bromocriptine in rat on day 9 and abortion prevention is achieved by WJ-MSCs injection via tail vein with or without JAK/STAT inhibitor. Here, we show that WJ-MSCs significantly lower the rate of embryo resorption of spontaneous abortion by reducing Th1-related cytokines while increasing Th2 and Th3-related cytokines in JAK/STAT-dependent manner. Together, our observation of WJ-MSCs in spontaneous abortion prevention will shed new light on potential therapeutic strategy development.

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Differential immunomodulation of human mesenchymal stromal cells from various sources in an inflammation mimetic milieu

Cited by 4 publications

References 41 publications

Human Wharton's jelly‐derived mesenchymal stem cells prevent pregnancy loss in a rat by JAK/STAT‐mediated immunomodulation

Human Wharton's jelly‐derived mesenchymal stem cells prevent pregnancy loss in a rat by JAK/STAT‐mediated immunomodulation

Interferon-γ priming enhances the therapeutic effects of menstrual blood-derived stromal cells in a mouse liver ischemia-reperfusion model

Human Wharton’s jelly-derived mesenchymal stem cells prevent pregnancy loss in a rat by JAK/STAT-mediated immunomodulation

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