Mitochondrial Transfer from Mesenchymal Stem Cells to Macrophages Restricts Inflammation and Alleviates Kidney Injury in Diabetic Nephropathy Mice via PGC-1α Activation

Yuan, Yujia; Yuan, Longhui; Li, Lan; Liu, Fei; Liu, Jingping; Chen, Younan; Cheng, Jun; Liu, Yanrong

doi:10.1002/stem.3375

Cited by 65 publications

(47 citation statements)

References 46 publications

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“…Abbreviations: VEGF: vascular endothelial growth factor; TGF-β: transforming growth factor-β; IL-1Ra: interleukin-1 receptor agonist; ER: endoplasmic reticulum; ROS: reactive oxygen species; AKT: protein kinase B; AMPK: AMP-activated protein kinase; HFD: high-fat diet; GCK: glucokinase; L-PK: liver pyruvate kinase; PFK: 6phosphofructo-1-kinase; PGC-1α: peroxisome proliferator γ-activated receptor coactivator 1-α; PEPCK: phosphoenolpyruvate carboxykinase; G6Pase: glucose-6-phosphatase; AKP: alkaline phosphatase; LDH: lactate dehydrogenase; ALT: alanine aminotransferase; AST: aspartate aminotransferase. 7 Stem Cells International mitochondrial functions [57,58]. Rackham et al demonstrated that mitochondria of MSCs could be transferred to β-cells under hypoxia conditions for replenishment.…”

Section: β-Cell Regeneration Mscs Promote Insulin Production By Facil...mentioning

confidence: 99%

Mesenchymal Stem Cells (MSCs): A Novel Therapy for Type 2 Diabetes

Gao

Zhang

Liang

et al. 2022

Stem Cells International

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Although plenty of drugs are currently available for type 2 diabetes mellitus (T2DM), a subset of patients still failed to restore normoglycemia. Recent studies proved that symptoms of T2DM patients who are unresponsive to conventional medications could be relieved with mesenchymal stem/stromal cell (MSC) therapy. However, the lack of systematic summary and analysis for animal and clinical studies of T2DM has limited the establishment of standard guidelines in anti-T2DM MSC therapy. Besides, the therapeutic mechanisms of MSCs to combat T2DM have not been thoroughly understood. In this review, we present an overview of the current status of MSC therapy in treating T2DM for both animal studies and clinical studies. Potential mechanisms of MSC-based intervention on multiple pathological processes of T2DM, such as β-cell exhaustion, hepatic dysfunction, insulin resistance, and systemic inflammation, are also delineated. Moreover, we highlight the importance of understanding the pharmacokinetics (PK) of transplanted cells and discuss the hurdles in MSC-based T2DM therapy toward future clinical applications.

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Section: β-Cell Regeneration Mscs Promote Insulin Production By Facil...mentioning

confidence: 99%

Mesenchymal Stem Cells (MSCs): A Novel Therapy for Type 2 Diabetes

Gao

Zhang

Liang

et al. 2022

Stem Cells International

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“…This in turn promotes M2 macrophages polarization and might be recognized as a critical immunomodulatory mechanism that protects tissue from inflammation and resulting injury. Recent study demonstrated, that in response to reactive oxygen species (ROS) overproduction and damage-associated molecular patterns (DAMPs) including defective and mutated mtDNA accumulation, MSCs cells tend to donate healthy mitochondria to injured cells [ 13 ]. Transferred mitochondria through mitochondrial fusion subsequently enhance donor cells ATP production, improve oxidative phosphorylation, and thus protect against cells apoptosis [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Mitochondria transfer restores fibroblasts-like synoviocytes (FLS) plasticity in LPS-induced, in vitro synovitis model

Kornicka

Groborz²,

Lynda

et al. 2022

Cell Commun Signal

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Background Synovitis (SI) is one of the most common and serious orthopedic diseases in horses of different age, breed and sex, which contributes to the development of osteoarthritis. The burden of SI includes economic loss and represents a real challenge for current veterinary health care. At the molecular level, fibroblasts-like synoviocytes (FLS) are recognized as major cell populations involved in SI pathogenesis. In the course of SI, FLSs are losing their protective and pro-regenerative cytological features, become highly proliferative and initiate various stress signaling pathways. Methods Fibroblast-like synoviocytes were treated with LPS in order to generate SI in vitro model. Mitochondria were isolated from peripheral blood derived mononuclear cells and co-cultured with FLS. After 24 h of culture, cells were subjected to RT-qPCR, western blot, cytometric and confocal microscopy analysis. Results Mitochondrial transfer (MT) was observed in vitro studies using confocal microscopy. Further studies revealed, that MT to LPS-treated FLS reduced cell proliferation, modulated apoptosis and decreased inflammatory response. Overall, MT Resulted in the considerable recovery of recipient cells cytophysiological properties. Conclusions Presented data provides evidence that mitochondria transfersignificantly modulate FLS proliferative and metabolic activity through improved mitochondrial biogenesis and dynamics in activated FLS. Obtained results for the first time demonstrate that horizontal MT might be considered as a therapeutic tool for synovitis treatment; however, further clinical studies are strongly required.

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“…However, in addition to differentiating into osteoblast line cells, bone marrow-derived mesenchymal stem cells (BMSCs) were shown to have an immunoregulatory function by modulating immune responses via cell contact-dependent or paracrine mechanisms ( 115 ). Regarding non-specific immunity, BMSCs can induce a shift in macrophages from an M1 to M2 phenotype ( 116 ), and the interaction between BMSCs and macrophages contributes to the restriction of inflammation ( 117 ). Although BMSCs can not affect the proliferation of NK cells, they reduce the IFN-γ production of NK cells ( 118 ).…”

Section: Discussionmentioning

confidence: 99%

Immunoporosis: Role of immune system in the pathophysiology of different types of osteoporosis

et al. 2022

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Osteoporosis is a skeletal system disease characterized by low bone mass and altered bone microarchitecture, with an increased risk of fractures. Classical theories hold that osteoporosis is essentially a bone remodeling disorder caused by estrogen deficiency/aging (primary osteoporosis) or secondary to diseases/drugs (secondary osteoporosis). However, with the in-depth understanding of the intricate nexus between both bone and the immune system in recent decades, the novel field of “Immunoporosis” was proposed by Srivastava et al. (2018, 2022), which delineated and characterized the growing importance of immune cells in osteoporosis. This review aimed to summarize the response of the immune system (immune cells and inflammatory factors) in different types of osteoporosis. In postmenopausal osteoporosis, estrogen deficiency-mediated alteration of immune cells stimulates the activation of osteoclasts in varying degrees. In senile osteoporosis, aging contributes to continuous activation of the immune system at a low level which breaks immune balance, ultimately resulting in bone loss. Further in diabetic osteoporosis, insulin deficiency or resistance-induced hyperglycemia could lead to abnormal regulation of the immune cells, with excessive production of proinflammatory factors, resulting in osteoporosis. Thus, we reviewed the pathophysiology of osteoporosis from a novel insight-immunoporosis, which is expected to provide a specific therapeutic target for different types of osteoporosis.

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Mitochondrial Transfer from Mesenchymal Stem Cells to Macrophages Restricts Inflammation and Alleviates Kidney Injury in Diabetic Nephropathy Mice via PGC-1α Activation

Cited by 65 publications

References 46 publications

Mesenchymal Stem Cells (MSCs): A Novel Therapy for Type 2 Diabetes

Mesenchymal Stem Cells (MSCs): A Novel Therapy for Type 2 Diabetes

Mitochondria transfer restores fibroblasts-like synoviocytes (FLS) plasticity in LPS-induced, in vitro synovitis model

Immunoporosis: Role of immune system in the pathophysiology of different types of osteoporosis

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