High-efficiency quantitative control of mitochondrial transfer based on droplet microfluidics and its application on muscle regeneration

Sun, Jiayu; Lo, Hiu Tung; Fan, Lei; Yiu, Tsz Lam; Shakoor, Adnan; Li, Gang; Lee, Wayne; Sun, Dong

doi:10.1126/sciadv.abp9245

Cited by 31 publications

(15 citation statements)

References 59 publications

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“…The transfer of mitochondria to cell therapy products before their administration can enhance therapeutic outcomes; however, current techniques suffer from low transfer efficiency. Sun et al developed a high-efficiency mitochondrial transfer technique by coencapsulating and coculturing mitochondria and cells in droplets . The spatial confinement plays a major role in favoring endocytosis of mitochondria by the cells.…”

Section: Droplet Microfluidicsmentioning

confidence: 99%

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Advances in Microfluidics: Technical Innovations and Applications in Diagnostics and Therapeutics

Aubry

Lee

2023

Anal. Chem.

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Section: Droplet Microfluidicsmentioning

confidence: 99%

“…Sun et al developed a high-efficiency mitochondrial transfer technique by coencapsulating and coculturing mitochondria and cells in droplets. 64 The spatial confinement plays a major role in favoring endocytosis of mitochondria by the cells.…”

Section: ■ Instrumentationmentioning

confidence: 99%

Advances in Microfluidics: Technical Innovations and Applications in Diagnostics and Therapeutics

Aubry

Lee

2023

Anal. Chem.

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“… 149 The technique is variable but mostly involves the delivery of autologous mitochondria from bone marrow mesenchymal cells, for instance, either intravenously or by direct injection into affected tissue. 150 , 151 Since the second semester of 2021, a phase 1/2a clinical trial targeting DM/PM has been enrolling patients to define safety and tolerability of a single injection of allogeneic mitochondria ( ClinicalTrials.gov Identifier: NCT04976140). Completion is expected by the middle of 2023.…”

Section: Treatmentmentioning

confidence: 99%

The Emerging Role of Mitochondrial Dysfunction in the Pathogenesis of Idiopathic Inflammatory Myopathies

Gonzalez-Chapa¹,

Macêdo²,

Lood³

2023

Rambam Maimonides Med J

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Increasing evidence points towards mitochondria as crucial players in the initiation and progression of auto-immune and degenerative disorders, to which impaired cell metabolism is but a facet of the subjacent etiopathogenesis. This review aims to introduce the reader to essential concepts of mitochondrial abnormalities in idiopathic inflammatory myopathy (IIM), underscoring inclusion-body myositis and dermatomyositis. Far surpassing the initial simplistic view of being responsible for energy generation, mitochondria have gathered attention regarding their role in inflammatory processes, being able to fuel autoimmunity, as shown by the presence of anti-mitochondrial antibodies (AMAs) in up to 10% of IIM patients. As cellular respiration takes place, mitochondrial metabolites might help to shape the pro-inflammatory milieu in affected muscle, beyond generating reactive oxygen species, which are well-recognized inducers of damage-associated molecular patterns. A series of mitochondrial components might facilitate the sterile activation of pro-inflammatory cells and the production of several cytokines responsible for enhancing auto-immune responses. Marked variation in the mitochondrial genome has also been reported in IIM patients. As such, we summarize key historical and recent advances linking aberrations and instabilities of mitochondrial DNA to impaired muscle function. Besides discussing mitochondrial dysfunction as an essential part of IIM development, we also highlight possible associations between presence of AMAs and a particular phenotype of IIM, with its own characteristic clinical and radiological pattern. Finally, we present promising treatment approaches targeting mitochondria, while briefly discussing experimental models for gaining deeper insight into the disease process, and ultimately leading to novel drug development.

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“…Centrifugation is another method that promote the transplantation of mitochondria, which was first applied in improving the atrophic syndrome [21]. In addition, the droplet-based microfluidic system in enhancing the transplantation of mitochondria was also reported [22]. In the molecular aspect, proteins such as Miro 1 and Miro 2 proteins were found to be involved in mitochondrial trafficking [23].…”

Section: Introductionmentioning

confidence: 99%

Transplanting Heterologous Mitochondria from Human Umbilical Vein Endothelial Cells Reduces the Malignancy of Melanoma Cells

Kuo¹,

Cheng²,

Tsai³

et al. 2023

Preprint

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The development of using mitochondrial transplantation in medical therapy are currently discussed. According to the endosymbiotic theory, the movement of mitochondria between different cells is possible. Therefore, an idea of transferring the mitochondria purified from the cells with a limited lifespan to shorten the lifespan of immortal cancer cells was generated. Human umbilical vein endothelial cell (HUVEC) is a kind of primary cell with a limited lifespan. In the present study, the mitochondria purified from HUVEC were applied to alter the malignance of B16F10 melanoma cell. In the comparison of the basic function of mitochondria, HUVEC mitochondria exhibited a higher mitochondrial membrane potential (MMP), while the lower levels in ATP, mitochondrial DNA (mt-DNA) and mitochondrial protein (mt-protein) as compared to melanoma B16F10. After transplanted the B16F10 with HUVEC mitochondria, the migration, invasion, and the proteins involved in cancer stemness were decreased, however, the proteins involved in cell proliferation, such as cyclin D1 and cyclin E1 were increased. In addition, the levels of ATP, mt-DNA and mt-protein of B16F10 were also reduced. As for the dynamics of mitochondria, the reduced expressions of DRP1 and LC3 II revealed that transferred mitochondria can attenuate the mitophagy of B16F10. In mice, inoculated the B16F10 carrying the transplanted HUVEC mitochondria resulted in the larger size of tumor, which is corresponded to the higher levels of cyclin D1 and E1. Interestingly, the lower expressions of N-cadherin, α-SMA and MMP-9 reveled the tumor were decreased in mesenchymal characteristics. Therefore, despite the HUVEC mitochondria did not inhibit the proliferation of B16F10, the metastatic characteristic was reduced.

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High-efficiency quantitative control of mitochondrial transfer based on droplet microfluidics and its application on muscle regeneration

Cited by 31 publications

References 59 publications

Advances in Microfluidics: Technical Innovations and Applications in Diagnostics and Therapeutics

Advances in Microfluidics: Technical Innovations and Applications in Diagnostics and Therapeutics

The Emerging Role of Mitochondrial Dysfunction in the Pathogenesis of Idiopathic Inflammatory Myopathies

Transplanting Heterologous Mitochondria from Human Umbilical Vein Endothelial Cells Reduces the Malignancy of Melanoma Cells

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