G-CSF supports long-term muscle regeneration in mouse models of muscular dystrophy

Hayashiji, Nozomi; Yuasa, Shinsuke; Miyagoe-Suzuki, Yuko; Hara, Motoki; Ito, Naoki; Hashimoto, Hisayuki; Kusumoto, Dai; Seki, Tomohisa; Tohyama, Shugo; Kodaira, Masaki; Kunitomi, Akira; Kashimura, Shin; Takei, Makoto; Saito, Yuki; Okata, Shinichiro; Egashira, Toru; Endo, Jin; Sasaoka, Toshikuni; Takeda, Shin’ichi; Fukuda, Keiichi

doi:10.1038/ncomms7745

Cited by 43 publications

(39 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Likewise, 80% of human MRC are quiescent mononucleated Pax7 + /MyoD − cells, and proliferate in GM while retaining a high differentiation potential in DM. Two markers, CD82 and CD114 (G-CSF receptor), recently identified in myogenic precursor cell populations 32, 33 were also expressed at similar level by human MPC and human MRC.…”

Section: Discussionmentioning

confidence: 77%

Human myogenic reserve cells are quiescent stem cells that contribute to muscle regeneration after intramuscular transplantation in immunodeficient mice

Laumonier

Bermont

Hoffmeyer

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Satellite cells, localized within muscles in vivo, are Pax7+ muscle stem cells supporting skeletal muscle growth and regeneration. Unfortunately, their amplification in vitro, required for their therapeutic use, is associated with reduced regenerative potential. In the present study, we investigated if human myogenic reserve cells (MRC) obtained in vitro, represented a reliable cell source for muscle repair. For this purpose, primary human myoblasts were freshly isolated and expanded. After 2 days of differentiation, 62 ± 2.9% of the nuclei were localized in myotubes and 38 ± 2.9% in the mononucleated non-fusing MRC. Eighty percent of freshly isolated human MRC expressed a phenotype similar to human quiescent satellite cells (CD56+/Pax7+/MyoD−/Ki67− cells). Fourteen days and 21 days after cell transplantation in immunodeficient mice, live human cells were significantly more numerous and the percentage of Pax7+/human lamin A/C+ cells was 2 fold higher in muscles of animals injected with MRC compared to those injected with human myoblasts, despite that percentage of spectrin+ and lamin A/C+ human fibers in both groups MRC were similar. Taken together, these data provide evidence that MRC generated in vitro represent a promising source of cells for improving regeneration of injured skeletal muscles.

show abstract

Section: Discussionmentioning

confidence: 77%

Human myogenic reserve cells are quiescent stem cells that contribute to muscle regeneration after intramuscular transplantation in immunodeficient mice

Laumonier

Bermont

Hoffmeyer

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…As G‐CSFR was recently reported to be asymmetrically distributed in about 20% of activated Pax7 SCs (Hayashiji et al , ), we reasoned that the asymmetric distribution of G‐CSFR response to G‐CSF mediated asymmetric division. Firstly, single fibers isolated from the EDL and Soleus muscles of Pax7‐nGFP mice were treated with G‐CSF for 48 h and immunostained with anti‐G‐CSFR (Fig G).…”

Section: Resultsmentioning

confidence: 92%

Muscle‐secreted granulocyte colony‐stimulating factor functions as metabolic niche factor ameliorating loss of muscle stem cells in aged mice

Chen

et al. 2019

The EMBO Journal

View full text Add to dashboard Cite

The function and number of muscle stem cells (satellite cells, SCs) decline with muscle aging. Although SCs are heterogeneous and different subpopulations have been identified, it remains unknown whether a specific subpopulation of muscle SCs selectively decreases during aging. Here, we find that the number of SCs expressing high level of transcription factor Pax7 (Pax7Hi) is dramatically reduced in aged mice. Myofiber‐secreted granulocyte colony‐stimulating factor (G‐CSF) regulates age‐dependent loss of Pax7Hi cells, as the Pax7Hi SCs are replenished by exercise‐induced G‐CSF in aged mice. Mechanistically, we show that transcription of G‐CSF (Csf3) gene in myofibers is regulated by MyoD in a metabolism‐dependent manner. Furthermore, myofiber‐secreted G‐CSF acts as a metabolic niche factor required for establishing and maintaining the Pax7Hi SC subpopulation in adult and physiological aged mice by promoting the asymmetric division of Pax7Hi and Pax7Mi SCs. Together, our findings uncover that muscles provide a metabolic niche regulating Pax7 SC heterogeneity in mice.

show abstract

“…However, it should be pointed out that the higher infused cell doses in the T7 group were associated with neurodevelopmental improvement, because there is, as yet, no evidence that cell dose has an effect on neurologic improvements. In addition, Hara [20] and Hayashiji [21] reported that G-CSF positively affects the recovery of muscle mass, therefore delayed effect of G-CSF on muscle regeneration may be contributed to synergistic improvement of neurodevelopmental functions in T7 group. Contrary to the results from neurodevelopment tests, MRI-DTI showed greater increase of FA values in the CRL, PLL, and Genu ROIs in the T1 group than in the T7 group, indicating that the neuroregenerative effect of G-CSF coupled with mPBMC infusion is higher at 1 month than at 7 months.…”

Section: Discussionmentioning

confidence: 99%

Neuroregenerative potential of intravenous G-CSF and autologous peripheral blood stem cells in children with cerebral palsy: a randomized, double-blind, cross-over study

et al. 2017

View full text Add to dashboard Cite

ObjectiveWe performed a randomized, double-blind, cross-over study to assess the neuroregenerative potential of intravenous granulocyte colony-stimulating factor (G-CSF) followed by infusion of mobilized peripheral blood mononuclear cells (mPBMCs) in children with cerebral palsy (CP).MethodsChildren with non-severe CP were enrolled in this study. G-CSF was administered for 5 days, then mPBMCs were collected by apheresis and cryopreserved. One month later (M1), recipients were randomized to receive either mPBMCs or a placebo infusion, and these treatment groups were switched at 7 months (M7) and observed for another 6 months (M13). We assessed the efficacy of treatment by evaluating neurodevelopmental tests, as well as by brain magnetic resonance imaging-diffusion tensor imaging (MRI-DTI) and 18F-fluorodeoxyglucose (FDG) brain positron emission tomography-computed tomography (PET-CT) scanning to evaluate the anatomical and functional changes in the brain.ResultsFifty-seven patients aged 4.3 ± 1.9 (range 2–10) years and weighing 16.6 ± 4.9 (range 11.6–56.0) kg were enrolled in this study. The administration of G-CSF as well as the collection and reinfusion of mPBMCs were safe and tolerable. The yield of mPBMCs was comparable to that reported in studies of pediatric donors without CP and patients with nonhematologic diseases. 42.6% of the patients responded to the treatment with higher neurodevelopmental scores than would normally be expected. In addition, larger changes in neurodevelopment test scores were observed in the 1 month after G-CSF administration (M0–M1) than during the 6 months after reinfusion with mPBMCs or placebo (M1–M7 or M7–M13). Patients who received G-CSF followed by mPBMC infusion at 7 months (T7 group) demonstrated significantly more neurodevelopmental improvement than patients who received G-CSF followed by mPBMC infusion at 1 month (T1 group). In contrast to the results of neurodevelopment tests, the results of MRI-DTI at the end of this study showed greater improvement in the T1 group. Although we observed metabolic changes to the cerebellum, thalamus and cerebral cortex in the 18F-FDG brain PET-CT scans, there were no significant differences in such changes between the mPBMC and placebo group or between the T1 and T7 group.ConclusionsNeurodevelopmental improvement was seen in response to intravenous G-CSF followed by mPBMC reinfusion, particularly to the G-CSF alone even without mPBMC reinfusion. Further studies using a larger number of mPBMCs for the infusion which could be collected by repeated cycles of apheresis or using repeated cycles of G-CSF alone, are needed to clarify the effect of mPBMC reinfusion or G-CSF alone (Trial registration: ClinicalTrials.gov, NCT02983708. Registered 5 December, 2016, retrospectively registered).

show abstract

G-CSF supports long-term muscle regeneration in mouse models of muscular dystrophy

Cited by 43 publications

References 42 publications

Human myogenic reserve cells are quiescent stem cells that contribute to muscle regeneration after intramuscular transplantation in immunodeficient mice

Human myogenic reserve cells are quiescent stem cells that contribute to muscle regeneration after intramuscular transplantation in immunodeficient mice

Muscle‐secreted granulocyte colony‐stimulating factor functions as metabolic niche factor ameliorating loss of muscle stem cells in aged mice

Neuroregenerative potential of intravenous G-CSF and autologous peripheral blood stem cells in children with cerebral palsy: a randomized, double-blind, cross-over study

Contact Info

Product

Resources

About