Direct Reprogramming of Mouse Fibroblasts into Functional Skeletal Muscle Progenitors

Bar‐Nur, Ori; Gerli, M; Stefano, Bruno Di; Almada, Albert E.; Galvin, Amy; Coffey, Amy; Huebner, Aaron J.; Feige, Peter; Verheul, Cassandra; Cheung, Priscilla; Payzin‐Dogru, Duygu; Paisant, Sylvain; Anselmo, Anthony; Sadreyev, Ruslan I.; Ott, Harald C.; Tajbakhsh, Shahragim; Rudnicki, Michael A.; Wagers, Amy J.; Hochedlinger, Konrad

doi:10.1016/j.stemcr.2018.04.009

Cited by 88 publications

(122 citation statements)

References 45 publications

(57 reference statements)

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“…In a recent study, Bar‐Nur et al . reported a robust approach for the direct conversion of adult mouse fibroblasts to myogenic progenitor cells via ectopic overexpression of the transcription factor MyoD …”

Section: Advances In Treatment Of Local Muscle Injuriesmentioning

confidence: 99%

Cell therapy to improve regeneration of skeletal muscle injuries

Qazi

Duda

Ort

et al. 2019

J cachexia sarcopenia muscle

106

128

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Diseases that jeopardize the musculoskeletal system and cause chronic impairment are prevalent throughout the Western world. In Germany alone, ~1.8 million patients suffer from these diseases annually, and medical expenses have been reported to reach 34.2bn Euros. Although musculoskeletal disorders are seldom fatal, they compromise quality of life and diminish functional capacity. For example, musculoskeletal disorders incur an annual loss of over 0.8 million workforce years to the German economy. Among these diseases, traumatic skeletal muscle injuries are especially problematic because they can occur owing to a variety of causes and are very challenging to treat. In contrast to chronic muscle diseases such as dystrophy, sarcopenia, or cachexia, traumatic muscle injuries inflict damage to localized muscle groups. Although minor muscle trauma heals without severe consequences, no reliable clinical strategy exists to prevent excessive fibrosis or fatty degeneration, both of which occur after severe traumatic injury and contribute to muscle degeneration and dysfunction. Of the many proposed strategies, cell‐based approaches have shown the most promising results in numerous pre‐clinical studies and have demonstrated success in the handful of clinical trials performed so far. A number of myogenic and non‐myogenic cell types benefit muscle healing, either by directly participating in new tissue formation or by stimulating the endogenous processes of muscle repair. These cell types operate via distinct modes of action, and they demonstrate varying levels of feasibility for muscle regeneration depending, to an extent, on the muscle injury model used. While in some models the injury naturally resolves over time, other models have been developed to recapitulate the peculiarities of real‐life injuries and therefore mimic the structural and functional impairment observed in humans. Existing limitations of cell therapy approaches include issues related to autologous harvesting, expansion and sorting protocols, optimal dosage, and viability after transplantation. Several clinical trials have been performed to treat skeletal muscle injuries using myogenic progenitor cells or multipotent stromal cells, with promising outcomes. Recent improvements in our understanding of cell behaviour and the mechanistic basis for their modes of action have led to a new paradigm in cell therapies where physical, chemical, and signalling cues presented through biomaterials can instruct cells and enhance their regenerative capacity. Altogether, these studies and experiences provide a positive outlook on future opportunities towards innovative cell‐based solutions for treating traumatic muscle injuries—a so far unmet clinical need.

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Section: Advances In Treatment Of Local Muscle Injuriesmentioning

confidence: 99%

Cell therapy to improve regeneration of skeletal muscle injuries

Qazi

Duda

Ort

et al. 2019

J cachexia sarcopenia muscle

106

128

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“…These reprogramming assays have been done in HSCs, 66,67 MSCs, 68,69 NSCs, 70 intestinal progenitor cells, 71 and skeletal muscle progenitors. 72 Though many of these studies were performed in young animals, they suggest the potential for manipulation of adult, and even aged, cells to generate tissue-specific stem cells. In an aged paradigm, reprogrammed stem cells may be able to compensate for stem cell populations that have become depleted or functionally impaired.…”

Section: Reprogrammingmentioning

confidence: 99%

Restoring aged stem cell functionality: Current progress and future directions

2020

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Stem cell dysfunction is a hallmark of aging, associated with the decline of physical and cognitive abilities of humans and other mammals [Cell 2013;153:1194]. Therefore, it has become an active area of research within the aging and stem cell fields, and various techniques have been employed to mitigate the decline of stem cell function both in vitro and in vivo. While some techniques developed in model organisms are not directly translatable to humans, others show promise in becoming clinically relevant to delay or even mitigate negative phenotypes associated with aging. This review focuses on diet, treatment, and small molecule interventions that provide evidence of functional improvement in at least one type of aged adult stem cell.

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“…Pax7 staining was performed as previously described [51]. Slides were cross-linked with 4% PFA, washed with 1xPBS, incubated for 30 minutes with 2% BSA, dissolved in PBS and 0.1% Triton-X-100, followed by 15 minutes incubation with 10% donkey serum (017-000-121, Jackson ImmunoResearch, Cambridgeshire, UK) diluted in PBS.…”

Section: Immunofluorescencementioning

confidence: 99%

Exercise promotes satellite cell contribution to myofibers in a load-dependent manner

Masschelein

D’Hulst

Zvick

et al. 2020

Preprint

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Background Satellite cells (SCs) are required for muscle repair following injury and are involved in muscle remodeling upon muscular contractions. Exercise stimulates SC accumulation and myonuclear accretion. To what extent exercise training at different mechanical loads drive SC contribution to myonuclei however is unknown. Results By performing SC fate tracing experiments, we show that 8-weeks of voluntary wheel running increased SC contribution to myonuclei in mouse plantar flexor muscles in a load-dependent but fiber type-independent manner. Increased SC fusion however was not exclusively linked to muscle hypertrophy as wheel running without external load substantially increased SC fusion in the absence of fiber hypertrophy. Due to nuclear propagation, nuclear fluorescent fate tracing mouse models were inadequate to quantify SC contribution to myonuclei. Ultimately, by performing fate tracing at the DNA level, we show that SC contribution mirrors myonuclear accretion during exercise. Conclusions Collectively, these findings provide direct evidence that mechanical load during exercise independently promotes SC contribution to existing myofibers.

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Direct Reprogramming of Mouse Fibroblasts into Functional Skeletal Muscle Progenitors

Cited by 88 publications

References 45 publications

Cell therapy to improve regeneration of skeletal muscle injuries

Cell therapy to improve regeneration of skeletal muscle injuries

Restoring aged stem cell functionality: Current progress and future directions

Exercise promotes satellite cell contribution to myofibers in a load-dependent manner

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