Pulsed electromagnetic fields potentiate the paracrine function of mesenchymal stem cells for cartilage regeneration

Parate, Dinesh; Kadir, Nurul Dinah; Çelik, Cenk; Lee, Eng Hin; Hui, James; Franco‐Obregón, Alfredo; Yang, Zheng

doi:10.1186/s13287-020-1566-5

Cited by 66 publications

(66 citation statements)

References 68 publications

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“…Human umbilical cord-derived MSCs (HucMSCs) have higher proliferative potential and lower immunogenicity compared with those of other MSCs and have become an ideal choice in treating diabetes [7][8][9]. Increasing evidence has shown that MSCs exert therapeutic effects mainly through paracrine signaling [10]. As an important manifestation of paracrine signaling, exosomes have been considered to represent a promising cell-free therapy due to their multiple bioactivities and intercellular communication functions [11,12].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Mesenchymal stem cell-derived exosomes exert ameliorative effects in type 2 diabetes by improving hepatic glucose and lipid metabolism via enhancing autophagy

He¹,

Wang²,

Zhao³

et al. 2020

Stem Cell Res Ther

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Background: Mesenchymal stem cell (MSC)-based therapy is currently considered to be an effective treatment strategy for diabetes and hepatic disorders, such as liver cirrhosis and non-alcoholic fatty liver disease. Exosomes are important mediators of cellular connections, and increasing evidence has suggested that exosomes derived from MSCs may be used as direct therapeutic agents; their mechanisms of action, however, remain largely unclear. Here, we evaluated the efficacy and molecular mechanisms of human umbilical cord MSC-derived exosomes (HucMDEs) on hepatic glucose and lipid metabolism in type 2 diabetes mellitus (T2DM). Methods: HucMDEs were used to treat T2DM rats, as well as palmitic acid (PA)-treated L-O2 cells, in order to determine the effects of HucMDEs on hepatic glucose and lipid metabolism. To evaluate the changes in autophagy and potential signaling pathways, autophagy-related proteins (BECN1, microtubule-associated protein 1 light chain 3 beta [MAP 1LC3B]), autophagy-related genes (ATGs, ATG5, and ATG7), AMP-activated protein kinase (AMPK), and phosphorylated AMPK (p-AMPK) were assessed by Western blotting. Results: HucMDEs promoted hepatic glycolysis, glycogen storage, and lipolysis, and reduced gluconeogenesis. Additionally, autophagy potentially contributed to the effects of HucMDE treatment. Transmission electron microscopy revealed an increased formation of autophagosomes in HucMDE-treated groups, and the autophagy marker proteins, BECN1 and MAP 1LC3B, were also increased. Moreover, autophagy inhibitor 3-methyladenine significantly reduced the effects of HucMDEs on glucose and lipid metabolism in T2DM rats. Based on its phosphorylation status, we found that the AMPK signaling pathway was activated and induced autophagy in T2DM rats and PA-treated L-O2 cells. Meanwhile, the transfection of AMPK siRNA or application of the AMPK inhibitor, Comp C, weakened the therapeutic effects of HucMDEs on glucose and lipid metabolism.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Mesenchymal stem cell-derived exosomes exert ameliorative effects in type 2 diabetes by improving hepatic glucose and lipid metabolism via enhancing autophagy

He¹,

Wang²,

Zhao³

et al. 2020

Stem Cell Res Ther

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“…[5] The function of the cellular secretome is responsive to mitochondrial activation [57] and has recently been shown to be stimulated by the same magnetic field paradigm employed in this study. [58] Cell senescence moreover, is characterized by a senescence associated secretory phenotype [2][3][4] that is capable of inducing a contagious state of senescence to neighboring cells and tissues. [59] Therefore, given the enrichment of the healthy muscle secretome for diffusible factors, collectively known as myokines, possessing systemwide therapeutic and regenerative properties, [60][61][62] the possibility of activating, reinstating or fortifying the myokine response in muscle with CDVs derived from proliferative muscle cells in combination with magnetic field therapy merits further consideration.…”

Section: (9 Of 13)mentioning

confidence: 99%

“…PEMF Device: The PEMF device used in this study has been previously described. [5,20,58] All samples were exposed once for 10 min at a field amplitude of 1.5 mT. All PEMF-treated samples were compared to time-matched control samples (0 mT) that were manipulated in exactly the same as experimental samples, including placement into the PEMFgenerating apparatus for the designated time, except that the apparatus was not set to generate a magnetic field.…”

Section: (10 Of 13)mentioning

confidence: 99%

Cell‐Derived Vesicles as TRPC1 Channel Delivery Systems for the Recovery of Cellular Respiratory and Proliferative Capacities

et al. 2020

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Pulsed electromagnetic fields (PEMFs) are capable of specifically activating a TRPC1‐mitochondrial axis underlying cell expansion and mitohormetic survival adaptations. This study characterizes cell‐derived vesicles (CDVs) generated from C2C12 murine myoblasts and shows that they are equipped with the sufficient molecular machinery to confer mitochondrial respiratory capacity and associated proliferative responses upon their fusion with recipient cells. CDVs derived from wild type C2C12 myoblasts include the cation‐permeable transient receptor potential (TRP) channels, TRPC1 and TRPA1, and directly respond to PEMF exposure with TRPC1‐mediated calcium entry. By contrast, CDVs derived from C2C12 muscle cells in which TRPC1 has been genetically knocked‐down using CRISPR/Cas9 genome editing, do not. Wild type C2C12‐derived CDVs are also capable of restoring PEMF‐induced proliferative and mitochondrial activation in two C2C12‐derived TRPC1 knockdown clonal cell lines in accordance to their endogenous degree of TRPC1 suppression. C2C12 wild type CDVs respond to menthol with calcium entry and accumulation, likewise verifying TRPA1 functional gating and further corroborating compartmental integrity. Proteomic and lipidomic analyses confirm the surface membrane origin of the CDVs providing an initial indication of the minimal cellular machinery required to recover mitochondrial function. CDVs hence possess the potential of restoring respiratory and proliferative capacities to senescent cells and tissues.

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“…MSC transplantation is a fast-developing therapy in cell-based therapies and regenerative medicine [ 8 – 10 ]. Thus, they are regarded as a promising candidate for the repair and regeneration of some diseases [ 6 , 11 – 13 ].…”

Section: Introductionmentioning

confidence: 99%

The Efficacy of Mesenchymal Stem Cells in Therapy of Acute Kidney Injury Induced by Ischemia-Reperfusion in Animal Models

Zhou

Liao

Lin

et al. 2020

Stem Cells International

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Mesenchymal stem cells (MSCs), discovered and isolated from the bone marrow in the 1960s and with self-renewal capacity and multilineage differentiation potential, have valuable immunomodulatory abilities. Acute kidney injury (AKI) refers to rapid renal failure, which exhibits as quickly progressive decreasing excretion in few hours or days. This study was performed to assess the efficacy of MSCs in the treatment of AKI induced by ischemia-reperfusion using a meta-analysis method. A literature search using corresponding terms was performed in the following databases: Embase, Cochrane Library, PubMed, and ISI Web of Science databases up to Dec 31, 2019. Data for outcomes were identified, and the efficacy of MSCs for AKI was assessed using Cochrane Review Manager Version 5.3. Nineteen studies were eligible and recruited for this meta-analysis. MSC treatment can reduce the Scr levels at 1 day, 2 days, 3 days, 5 days, and >7 days (1 day: WMD=−0.56, 95% CI: -0.78, -0.34, P<0.00001; 2 days: WMD=−0.58, 95% CI: -0.89, -0.28, P=0.0002; 3 days: WMD=−0.65, 95% CI: -0.84, -0.45, P<0.00001; 5 days: WMD=−0.35, 95% CI: -0.54, -0.16, P=0.0003; and >7 days: WMD=−0.22, 95% CI: -0.36, -0.08, P=0.002) and can reduce the levels of BUN at 1 day, 2 days, 3 days, and 5 days (1 day: WMD=−11.72, 95% CI: -18.80, -4.64, P=0.001; 2 days: WMD=−33.60, 95% CI: -40.15, -27.05, P<0.00001; 3 days: WMD=−21.14, 95% CI: -26.15, -16.14, P<0.00001; and 5 days: WMD=−8.88, 95% CI: -11.06, -6.69, P<0.00001), and it also can reduce the levels of proteinuria at 3 days and >7 days and alleviate the renal damage in animal models of AKI. In conclusion, MSCs might be a promising therapeutic agent for AKI induced by ischemia-reperfusion.

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Pulsed electromagnetic fields potentiate the paracrine function of mesenchymal stem cells for cartilage regeneration

Cited by 66 publications

References 68 publications

RETRACTED ARTICLE: Mesenchymal stem cell-derived exosomes exert ameliorative effects in type 2 diabetes by improving hepatic glucose and lipid metabolism via enhancing autophagy

RETRACTED ARTICLE: Mesenchymal stem cell-derived exosomes exert ameliorative effects in type 2 diabetes by improving hepatic glucose and lipid metabolism via enhancing autophagy

Cell‐Derived Vesicles as TRPC1 Channel Delivery Systems for the Recovery of Cellular Respiratory and Proliferative Capacities

The Efficacy of Mesenchymal Stem Cells in Therapy of Acute Kidney Injury Induced by Ischemia-Reperfusion in Animal Models

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