Bone marrow–derived mesenchymal stromal cells ameliorate severe acute pancreatitis in rats via hemeoxygenase-1–mediated anti-oxidant and anti-inflammatory effects

Ma, Zhilong; Song, Guodong; Zhao, Dongbo; Liu, Dalu; Dai, Yuxiang; He, Zhigang; Qian, Daohai; Gong, Jian; Meng, Hui; Zhou, Bo; Yang, Tianshe; Zhang, Song

doi:10.1016/j.jcyt.2018.11.013

Cited by 26 publications

(15 citation statements)

References 37 publications

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“…Likewise, DNA oxidation and lipid peroxidation caused by cisplatin‐induced kidney damage are alleviated by exosomes from human umbilical cord‐derived MSCs (UC‐MSCs); these results were confirmed in vitro with renal proximal tubular cells 27 . Treatments with MSCs were also demonstrated to reduce levels of ROS in animal models of diabetic retinopathy and nephropathy, severe acute pancreatitis, ureteral obstruction‐induced kidney damage, Alzheimer's disease, and metabolic renovascular disease 24,28‐32 . Specifically, MSC treatments have been shown to reduce levels of H 2 O 2 in intestinal inflammation and several organs in a model of premature aging 33,34 .…”

Section: Effect Of Mscs On Oxidative Stress Biomarkers and Rosmentioning

confidence: 89%

“…Downregulation of NRF2 and HO‐1 has been observed after MSC treatment of chemotherapy‐induced pulmonary fibrosis and diabetic sensory neuropathy which may be explained by a reduction in oxidative stimuli 40,63 . Conversely, the antioxidant effects of MSCs in several other models associate with upregulation of HO‐1 such as radiation‐induced aortic injury, septic lung injury, pancreatitis, and renal injuries caused by altered oxygen tensions and cisplatin 30,82,92‐94 . HO‐1 was determined to partially contribute to the effects of MSCs in pancreatitis as its inhibition with zinc protoporphyrin negated some of the effects of MSC treatments, including upregulation of CAT and increased SOD activity, which may indicate that these processes are downstream of HO‐1 activity 30 .…”

Section: Antioxidative Mechanisms Of Mscsmentioning

confidence: 99%

“…Conversely, the antioxidant effects of MSCs in several other models associate with upregulation of HO‐1 such as radiation‐induced aortic injury, septic lung injury, pancreatitis, and renal injuries caused by altered oxygen tensions and cisplatin 30,82,92‐94 . HO‐1 was determined to partially contribute to the effects of MSCs in pancreatitis as its inhibition with zinc protoporphyrin negated some of the effects of MSC treatments, including upregulation of CAT and increased SOD activity, which may indicate that these processes are downstream of HO‐1 activity 30 . After MSC treatment of small bowel I/R injury, a larger number of HO‐1 expressing cells were observed which did not appear to completely colocalize with engrafted MSCs suggesting that treatments may increase HO‐1 expression in cells of the host 84 .…”

Section: Antioxidative Mechanisms Of Mscsmentioning

confidence: 99%

“…These effects have included a reduction in inflammatory cytokines TNFα, IFNγ, interleukin (IL)‐1β, IL‐6, IL‐9, and IL‐4; decreased expression of ROS producing enzymes NOX, MPO, and iNOS; as well as a net reduction in the infiltration of immune cells such as neutrophils (Table 1). The anti‐inflammatory effects of MSCs in pancreatitis were partially dependent on their expression of the antioxidant pathway enzyme HO‐1 30 . Previously, it was demonstrated in a model of sepsis that MSC treatments can reduce pro‐inflammatory cytokines in the serum and normalize thiol/disulfide redox pairings responsible for free radical scavenging 51 .…”

Section: Antioxidative Mechanisms Of Mscsmentioning

confidence: 99%

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The emerging antioxidant paradigm of mesenchymal stem cell therapy

Stavely

Nurgali

2020

Stem Cells Translational Medicine

120

101

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Mesenchymal stem cells (multipotent stromal cells; MSCs) have been under investigation for the treatment of diverse diseases, with many promising outcomes achieved in animal models and clinical trials. The biological activity of MSC therapies has not been fully resolved which is critical to rationalizing their use and developing strategies to enhance treatment efficacy. Different paradigms have been constructed to explain their mechanism of action, including tissue regeneration, trophic/anti‐inflammatory secretion, and immunomodulation. MSCs rarely engraft and differentiate into other cell types after in vivo administration. Furthermore, it is equivocal whether MSCs function via the secretion of many peptide/protein ligands as their therapeutic properties are observed across xenogeneic barriers, which is suggestive of mechanisms involving mediators conserved between species. Oxidative stress is concomitant with cellular injury, inflammation, and dysregulated metabolism which are involved in many pathologies. Growing evidence supports that MSCs exert antioxidant properties in a variety of animal models of disease, which may explain their cytoprotective and anti‐inflammatory properties. In this review, evidence of the antioxidant effects of MSCs in in vivo and in vitro models is explored and potential mechanisms of these effects are discussed. These include direct scavenging of free radicals, promoting endogenous antioxidant defenses, immunomodulation via reactive oxygen species suppression, altering mitochondrial bioenergetics, and donating functional mitochondria to damaged cells. Modulation of the redox environment and oxidative stress by MSCs can mediate their anti‐inflammatory and cytoprotective properties and may offer an explanation to the diversity in disease models treatable by MSCs and how these mechanisms may be conserved between species.

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Section: Effect Of Mscs On Oxidative Stress Biomarkers and Rosmentioning

confidence: 89%

Section: Antioxidative Mechanisms Of Mscsmentioning

confidence: 99%

Section: Antioxidative Mechanisms Of Mscsmentioning

confidence: 99%

Section: Antioxidative Mechanisms Of Mscsmentioning

confidence: 99%

See 2 more Smart Citations

The emerging antioxidant paradigm of mesenchymal stem cell therapy

Stavely

Nurgali

2020

Stem Cells Translational Medicine

120

101

View full text Add to dashboard Cite

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“…It is well documented that MPO activity is a key indicator reflecting the accumulation of polymorphonuclear neutrophils in the pancreatic tissues [29,30].…”

Section: Ctrp3 Over-expression Decreases Mpo Activity and Increases Smentioning

confidence: 99%

CTRP3 ameliorates cerulein-induced severe acute pancreatitis in mice via SIRT1/NF-κB/p53 axis

Wei

et al. 2020

Bioscience Reports

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Severe acute pancreatitis (SAP) is a common and life-threatening clinical acute abdominal disease. C1q/tumor necrosis factor-related protein 3 (CTRP3), a novel paralog of adiponectin, has been identified as a crucial regulator in multiple types of inflammatory disorders. However, the biological role of CTRP3 in SAP remains poorly understood. This study aimed to characterize the role of CTRP3 in SAP and illuminate the potential mechanisms involved. In the current study, SAP mouse models were induced by seven hourly intraperitoneal injection of cerulein (50 μg/kg) and an immediate intraperitoneal injection of lipopolysaccharide (10 mg/kg) after the last cerulein administration. Histological examination and serological analysis demonstrated that SAP mouse models were successfully established. Herein, we found that CTRP3 expression was significantly decreased in the pancreatic tissues of SAP mice compared with normal control mice. Furthermore, we explored the effects of CTRP3 rescue in SAP mice and discovered that CTRP3 over-expression attenuated pathological lesions, inhibited inflammatory mediator release and repressed acinar cell apoptosis. Notably, mechanistic studies revealed that CTRP3 over-expression suppressed NF-κB p65 phosphorylation and p53 acetylation to alleviate cerulein-induced SAP in mouse models through activation of silent information regulator 1 (SIRT1), a nicotinamide adenine dinucleotide-dependent protein deacetylase. Collectively, our data indicate that CTRP3 may exert its protective effects in SAP mice via regulation of SIRT1-mediated NF-κB and p53 signaling pathways, implying a promising therapeutic strategy against SAP.

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Mesenchymal stromal cell therapy for pancreatitis: Progress and challenges

Zhou

Yang

et al. 2021

Medicinal Research Reviews

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Pancreatitis is a common gastrointestinal disease with no effective therapeutic options, particularly for cases of severe acute and chronic pancreatitis (CP). Mesenchymal stromal cells (MSCs) are multipotent cells with diverse biological properties, including directional migration, paracrine, immunosuppressive, and antiinflammatory effects, which are considered an ideal candidate cell type for repairing tissue damage caused by various pathogenies. Several researchers have reported significant therapeutic efficacy of MSCs in animal models of acute and CP. However, the specific underlying mechanisms are yet to be clarified and clinical application of MSCs as pancreatitis therapy has rarely been reported. This review mainly focuses on the potential and challenges in clinical application of MSCs for treatment of acute and CP, along with discussion of the underlying molecular mechanisms.

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Bone marrow–derived mesenchymal stromal cells ameliorate severe acute pancreatitis in rats via hemeoxygenase-1–mediated anti-oxidant and anti-inflammatory effects

Cited by 26 publications

References 37 publications

The emerging antioxidant paradigm of mesenchymal stem cell therapy

The emerging antioxidant paradigm of mesenchymal stem cell therapy

CTRP3 ameliorates cerulein-induced severe acute pancreatitis in mice via SIRT1/NF-κB/p53 axis

Mesenchymal stromal cell therapy for pancreatitis: Progress and challenges

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