Human Skeletal Muscle Cells Derived from the Orbicularis Oculi Have Regenerative Capacity for Duchenne Muscular Dystrophy

Yamanaka, Yukito; Takenaka, Nana; Sakurai, Hiroyuki; Ueno, Masaki; Kinoshita, Shigeru; Sotozono, Chie; Sato, Takahiko

doi:10.3390/ijms20143456

Cited by 10 publications

(5 citation statements)

References 18 publications

(23 reference statements)

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“…To investigate the effects of microgravity on skeletal muscle atrophy, we utilized a 3D-clinorotation system to simulate microgravity conditions with human primary skeletal muscle hOM2 cells, which are derived from the orbicularis oculi ( Yamanaka et al, 2019 ). We observed that the proliferation of both myogenic cells and human iPS cells decreased in microgravity using the clinorotation ( Supplementary file 1 ), and it has been reported that initial myogenic differentiation to form myotubes is suppressed by fluid motion when the clinorotation is used ( Mansour et al, 2023 ).…”

Section: Resultsmentioning

confidence: 99%

“…To investigate the effects of microgravity on skeletal muscle atrophy, we utilized a 3Dclinorotation system to simulate microgravity conditions with human primary skeletal muscle hOM2 cells, which are derived from the orbicularis oculi (Yamanaka et al, 2019). We observed that the proliferation of both myogenic cells and human iPS cells decreased in microgravity (Supplementary file 1).…”

Section: Human Primary Myotubes Exhibit An Atrophic Phenotype In a Mi...mentioning

confidence: 99%

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The reciprocal regulation between mitochondrial-associated membranes and Notch signaling in skeletal muscle atrophy

Sato

Ito

Yamagata

et al. 2023

Preprint

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Skeletal muscle atrophy and the inhibition of muscle regeneration are known to occur as a natural consequence of aging, yet the underlying mechanisms that lead to these processes in atrophic myofibers remain largely unclear. Our research has revealed that the maintenance of proper mitochondrial-associated endoplasmic reticulum membranes (MAM) is vital for preventing skeletal muscle atrophy in microgravity environments. We discovered that the deletion of the mitochondrial fusion protein Mitofusin2 (MFN2), which serves as a tether for MAM, in human iPS cells or the reduction of MAM in differentiated myotubes caused by microgravity interfered with myogenic differentiation process and an increased susceptibility to muscle atrophy, as well as the activation of the Notch signaling pathway. The atrophic phenotype of differentiated myotubes in microgravity and the regenerative capacity of Mfn2-deficient muscle stem cells in dystrophic mice were both ameliorated by treatment with the gamma-secretase inhibitor DAPT. Our findings demonstrate how the orchestration of mitochondrial morphology in differentiated myotubes and regenerating muscle stem cells plays a crucial role in regulating Notch signaling through the interaction of MAM.

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Section: Resultsmentioning

confidence: 99%

Section: Human Primary Myotubes Exhibit An Atrophic Phenotype In a Mi...mentioning

confidence: 99%

The reciprocal regulation between mitochondrial-associated membranes and Notch signaling in skeletal muscle atrophy

Sato

Ito

Yamagata

et al. 2023

Preprint

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“…Clinical investigations conducted to date have attempted to treat a variety of conditions including muscular dystrophy, cardiac heart failure, and incontinence. 1 – 6 …”

Section: Introductionmentioning

confidence: 99%

“…Clinical investigations conducted to date have attempted to treat a variety of conditions including muscular dystrophy, cardiac heart failure, and incontinence. [1][2][3][4][5][6] Faecal incontinence (FI) is a condition that would particularly benefit from cell-based regenerative medicine to restore functional muscle. FI affects a large portion of the general population, with an estimated prevalence of (2%-15%).…”

Section: Introductionmentioning

confidence: 99%

Cell shape characteristics of human skeletal muscle cells as a predictor of myogenic competency: A new paradigm towards precision cell therapy

et al. 2023

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Skeletal muscle-derived cells (SMDC) hold tremendous potential for replenishing dysfunctional muscle lost due to disease or trauma. Current therapeutic usage of SMDC relies on harvesting autologous cells from muscle biopsies that are subsequently expanded in vitro before re-implantation into the patient. Heterogeneity can arise from multiple factors including quality of the starting biopsy, age and comorbidity affecting the processed SMDC. Quality attributes intended for clinical use often focus on minimum levels of myogenic cell marker expression. Such approaches do not evaluate the likelihood of SMDC to differentiate and form myofibres when implanted in vivo, which ultimately determines the likelihood of muscle regeneration. Predicting the therapeutic potency of SMDC in vitro prior to implantation is key to developing successful therapeutics in regenerative medicine and reducing implementation costs. Here, we report on the development of a novel SMDC profiling tool to examine populations of cells in vitro derived from different donors. We developed an image-based pipeline to quantify morphological features and extracted cell shape descriptors. We investigated whether these could predict heterogeneity in the formation of myotubes and correlate with the myogenic fusion index. Several of the early cell shape characteristics were found to negatively correlate with the fusion index. These included total area occupied by cells, area shape, bounding box area, compactness, equivalent diameter, minimum ferret diameter, minor axis length and perimeter of SMDC at 24 h after initiating culture. The information extracted with our approach indicates live cell imaging can detect a range of cell phenotypes based on cell-shape alone and preserving cell integrity could be used to predict propensity to form myotubes in vitro and functional tissue in vivo.

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“…OOMs, which are rich in vascular distribution, may have regenerative capacity and play vital roles in tissue grafting and facial burn injury repair [ 4 ]. Recent reports have shown the efficacy of the ocular muscle tissue as a rich source of stem cells with high proliferation, differentiation, and therapeutic capacities [ 5 , 6 , 7 , 8 , 9 ]. In this regard, OOM-derived stem cells (OOM-SCs) have garnered much attention and application recently for disease therapy and tissue regeneration due to their self-renewal, proliferation, and trilineage differentiation capacities [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

High Therapeutic and Esthetic Properties of Extracellular Vesicles Produced from the Stem Cells and Their Spheroids Cultured from Ocular Surgery-Derived Waste Orbicularis Oculi Muscle Tissues

et al. 2021

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Extracellular vesicles (EVs) are paracrine factors that mediate stem cell therapeutics. We aimed at evaluating the possible therapeutic and esthetic applications of EVs prepared from the waste human facial tissue-derived orbicularis oculi muscle stem cells (OOM-SCs). OOM-SCs were isolated from the ocular tissues (from elders and youngsters) after upper eyelid blepharoplasty or epiblepharon surgeries. EVs were prepared from the OOM-SCs (OOM-SC-EVs) and their three-dimensional spheroids. OOM-SCs showed a spindle-like morphology with trilineage differentiation capacity, positive expression of CD105, CD 90, and CD73, and negative expression of CD45 and CD34, and their stem cell properties were compared with other adult mesenchymal stem cells. OOM-SC-EVs showed a high inhibitory effect on melanin synthesis in B16F10 cells by blocking tyrosinase activity. OOM-SC-EVs treatment led to a significant attenuation of senescence-associated changes, a decrease in reactive oxygen species generation, and an upregulation of antioxidant genes. We demonstrated the regeneration activity of OOM-SC-EVs in in vitro wound healing of normal human dermal fibroblasts and upregulation of anti-wrinkle-related genes and confirmed the therapeutic potential of OOM-SC-EVs in the healing of the in vivo wound model. Our study provides promising therapeutic and esthetic applications of OOM-SC-EVs, which can be obtained from the ocular surgery-derived waste human facial tissues.

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Human Skeletal Muscle Cells Derived from the Orbicularis Oculi Have Regenerative Capacity for Duchenne Muscular Dystrophy

Cited by 10 publications

References 18 publications

The reciprocal regulation between mitochondrial-associated membranes and Notch signaling in skeletal muscle atrophy

The reciprocal regulation between mitochondrial-associated membranes and Notch signaling in skeletal muscle atrophy

Cell shape characteristics of human skeletal muscle cells as a predictor of myogenic competency: A new paradigm towards precision cell therapy

High Therapeutic and Esthetic Properties of Extracellular Vesicles Produced from the Stem Cells and Their Spheroids Cultured from Ocular Surgery-Derived Waste Orbicularis Oculi Muscle Tissues

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