Mesenchymal stem cells and their mitochondrial transfer: a double-edged sword

Cheng, Li; Cheung, Man-Chun; Han, Shuo; Zhang, Zhao; Chen, Ling; Chen, Junhui; Zeng, Hui; Qiu, Jianxiang

doi:10.1042/bsr20182417

Cited by 77 publications

(66 citation statements)

References 66 publications

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“…Furthermore, the protective effects of FTY-DC involve donation of mitochondria to splenic macrophages making them less immunogenic. In addition, our study for the first time to our knowledge demonstrates that BMDCs like mesenchymal stem cells (63) have the potential to donate mitochondria to induce an immunosuppressive phenotype in recipient cells.…”

Section: Discussionmentioning

confidence: 70%

FTY720 Regulates Mitochondria Biogenesis in Dendritic Cells to Prevent Kidney Ischemic Reperfusion Injury

Rousselle

Kuscu

et al. 2020

Front. Immunol.

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Dendritic cells (DCs) are central in regulating immune responses of kidney ischemia-reperfusion injury (IRI), and strategies to alter DC function may provide new therapeutic opportunities. Sphingosine 1-phosphate (S1P) modulates immunity through binding to its receptors (S1P1-5), and protection from kidney IRI occurs in mice treated with S1PR agonist, FTY720 (FTY). We tested if ex vivo propagation of DCs with FTY could be used as cellular therapy to limit the off-target effects associated with systemic FTY administration in kidney IRI. DCs have the ability of regulate innate and adaptive responses and we posited that treatment of DC with FTY may underlie improvements in kidney IRI. Herein, it was observed that treatment of bone marrow derived dendritic cells (BMDCs) with FTY induced mitochondrial biogenesis, FTY-treated BMDCs (FTY-DCs) showed significantly higher oxygen consumption rate and ATP production compared to vehicle treated BMDCs (Veh-DCs). Adoptive transfer of FTY-DCs to mice 24 h before or 4 h after IRI significantly protected the kidneys from injury compared to mice treated with Veh-DCs. Additionally, allogeneic adoptive transfer of C57BL/6J FTY-DCs into BALB/c mice equally protected the kidneys from IRI. FTY-DCs propagated from S1pr1-deficient DCs derived from CD11cCreS1pr1 fl/fl mice as well as blunting mitochondrial oxidation in wildtype (WT) FTY-DCs prior to transfer abrogated the protection observed by FTY-DCs. We queried if DC mitochondrial content alters kidney responses after IRI, a novel but little studied phenomenon shown to be integral to regulation of the immune response. Transfer of mitochondria rich FTY-DCs protects kidneys from IRI as transferred FTY-DCs donated their mitochondria to recipient splenocytes (i.e., macrophages) and prior splenectomy abrogated this protection. Adoptive transfer of FTY-DCs either prior to or after ischemic injury protects kidneys from IRI demonstrating a potent role for donor DC-mitochondria in FTY's efficacy. This is the first evidence, to our knowledge, that DCs have the potential to protect against kidney injury by donating mitochondria to splenic macrophages to alter their bioenergetics thus making them anti-inflammatory. In conclusion, the results support Rousselle et al. Transfer of FTY-DC Prevents Kidney IRI that ex vivo FTY720-induction of the regulatory DC phenotype could have therapeutic relevance that can be preventively infused to reduce acute kidney injury.

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Section: Discussionmentioning

confidence: 70%

FTY720 Regulates Mitochondria Biogenesis in Dendritic Cells to Prevent Kidney Ischemic Reperfusion Injury

Rousselle

Kuscu

et al. 2020

Front. Immunol.

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“…Inflammation-driven mitochondrial transfer of MSC to neighbor cells including retinal cells and cancer cells were also reported recently [73]. It should be stressed that the therapeutic effects of MSCs and direction of mitochondrial transfer highly depend on the niche where MSCs is located, including in case of HCC [73]. It seems that the proinflammatory environment can enhance MSCs-mitochondrial transfer and MSC-mitochondrial transfer to T cells, which in turn trigger various immune cells, including CD4 + T cells [81].…”

Section: Mechanisms Of Msc-dependent Tumor Suppression In Liver Cancermentioning

confidence: 63%

“…Clearly, NF-kb signaling pathway play a critical role in HCC and therefore, the anti-inflammatory properties of MSCs were found remarkable in the earlier stages [72]. Another interesting mechanism of MSCs is through transfer of mitochondria as reported in several previous studies [73,74]. Mitochondria have been considered a key player involved in many biologic processes in health and disease, including in HCC [75][76][77][78][79].…”

Section: Mechanisms Of Msc-dependent Tumor Suppression In Liver Cancermentioning

confidence: 99%

“…Some proinflammatory cytokines such as Il-6 and TNF-α can induce MSCs skeletal rearrangement and form tunneling nanotubes (TNT) through which mitochondria mobility occurs from MSCs to neighbor cells [73,80]. Inflammation-driven mitochondrial transfer of MSC to neighbor cells including retinal cells and cancer cells were also reported recently [73]. It should be stressed that the therapeutic effects of MSCs and direction of mitochondrial transfer highly depend on the niche where MSCs is located, including in case of HCC [73].…”

Section: Mechanisms Of Msc-dependent Tumor Suppression In Liver Cancermentioning

confidence: 99%

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Melatonin and Mesenchymal Stem Cells as a Key for Functional Integrity for Liver Cancer Treatment

Elmahallawy

Mohamed

Abdo

et al. 2020

IJMS

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Hepatocellular carcinoma (HCC) is the most common hepatobiliary malignancy with limited therapeutic options. On the other hand, melatonin is an indoleamine that modulates a variety of potential therapeutic effects. In addition to its important role in the regulation of sleep–wake rhythms, several previous studies linked the biologic effects of melatonin to various substantial endocrine, neural, immune and antioxidant functions, among others. Furthermore, the effects of melatonin could be influenced through receptor dependent and receptor independent manner. Among the other numerous physiological and therapeutic effects of melatonin, controlling the survival and differentiation of mesenchymal stem cells (MSCs) has been recently discussed. Given its controversial interaction, several previous reports revealed the therapeutic potential of MSCs in controlling the hepatocellular carcinoma (HCC). Taken together, the intention of the present review is to highlight the effects of melatonin and mesenchymal stem cells as a key for functional integrity for liver cancer treatment. We hope to provide solid piece of information that may be helpful in designing novel drug targets to control HCC.

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“…The transfer of mitochondria upregulates gene expression following an ischemic injury while simultaneously aiding in the reprogramming of adult animal cardiomyocytes. Moreover, treating ischemic human umbilical vein endothelial cells (HUVECs) with BMSC-based mitochondrial transfer therapy limits apoptosis and rescues aerobic respiration [80].…”

Section: Stem Cellsmentioning

confidence: 99%

Stem Cells as Drug-like Biologics for Mitochondrial Repair in Stroke

et al. 2020

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Stroke is a devastating condition characterized by widespread cell death after disruption of blood flow to the brain. The poor regenerative capacity of neural cells limits substantial recovery and prolongs disruptive sequelae. Current therapeutic options are limited and do not adequately address the underlying mitochondrial dysfunction caused by the stroke. These same mitochondrial impairments that result from acute cerebral ischemia are also present in retinal ischemia. In both cases, sufficient mitochondrial activity is necessary for cell survival, and while astrocytes are able to transfer mitochondria to damaged tissues to rescue them, they do not have the capacity to completely repair damaged tissues. Therefore, it is essential to investigate this mitochondrial transfer pathway as a target of future therapeutic strategies. In this review, we examine the current literature pertinent to mitochondrial repair in stroke, with an emphasis on stem cells as a source of healthy mitochondria. Stem cells are a compelling cell type to study in this context, as their ability to mitigate stroke-induced damage through non-mitochondrial mechanisms is well established. Thus, we will focus on the latest preclinical research relevant to mitochondria-based mechanisms in the treatment of cerebral and retinal ischemia and consider which stem cells are ideally suited for this purpose.

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Mesenchymal stem cells and their mitochondrial transfer: a double-edged sword

Cited by 77 publications

References 66 publications

FTY720 Regulates Mitochondria Biogenesis in Dendritic Cells to Prevent Kidney Ischemic Reperfusion Injury

FTY720 Regulates Mitochondria Biogenesis in Dendritic Cells to Prevent Kidney Ischemic Reperfusion Injury

Melatonin and Mesenchymal Stem Cells as a Key for Functional Integrity for Liver Cancer Treatment

Stem Cells as Drug-like Biologics for Mitochondrial Repair in Stroke

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