Granulocyte Colony-Stimulating Factor and Its Potential Application for Skeletal Muscle Repair and Regeneration

Abstract

Granulocyte colony-stimulating factor (G-CSF) was originally discovered in the context of hematopoiesis. However, the identification of the G-CSF receptor (G-CSFR) being expressed outside the hematopoietic system has revealed wider roles for G-CSF, particularly in tissue repair and regeneration. Skeletal muscle damage, including that following strenuous exercise, induces an elevation in plasma G-CSF, implicating it as a potential mediator of skeletal muscle repair. This has been supported by preclinical studies and clinical trials investigating G-CSF as a potential therapeutic agent in relevant disease states. This review focuses on the growing literature associated with G-CSF and G-CSFR in skeletal muscle under healthy and disease conditions and highlights the current controversies.

Immunomodulation for the Treatment of Fungal Infections: Opportunities and Challenges

“…Adoptive T-cell therapy Stimulation of T-cells with antigen and infusion into the patient (Tramsen et al, 2014) Generation of an adequate number of fungal-specific T cells with sufficient purity is challenging (Papadopoulou et al, 2016) Monoclonal antibodies Avoid toxicity risks because they are directed specifically to pathogen epitopes, reduce durations of antifungal drug treatment (Casadevall et al, 2004;Cassone, 2008) Highly specific, high production costs (Chames et al, 2009) CAR T-cell therapies T-cells are genetically modified to express CAR and provide MHC unrestricted antigen recognition (Meiliana et al, 2016) Cytokine release syndrome and neurotoxicity (Kochenderfer et al, 2012;Brudno and Kochenderfer, 2016), longer time needed to generate autologous CAR T-cells (Neelapu et al, 2017), allogeneic T-cells may cause GvHD, and may be rapidly eliminated by the host immune system (Depil et al, 2020) Dendritic Cells (DCs) Leads to activation of specific T-cells and secretion of cytokines and chemokines. It can be used both in immunotherapy and vaccination (Lauruschkat et al, 2018) Cost inefficient, difficult to scale, and labor intensive (Lauruschkat et al, 2018) G-CSF Restores neutrophil counts (Wright et al, 2017) Lineage-specific (Costa, 1998), may stimulate leukemia (Rowe, 2000) GM-CSF Stimulates proliferation and differentiation of hematopoietic progenitor cells. Enhances antimicrobial function of mature neutrophils and monocytes against fungal targets (Safdar et al, 2013).…”

“…The combination therapy effectively treated the fungal infection and all children survived both the underlying malignancy and the fungal infection (Grigull et al, 2006 ). Moreover, in HIV-infected patients with Aspergillus hyphae, G-CSF was shown to reverse neutrophil dysfunction (Wright et al, 2017 ).…”

Autologous Cord Blood in Children with Cerebral Palsy: A Review

“…In a rodent model of HIE, MSCs exerted neuroprotective effects by enhancing autophagy through the BDNF/mTOR signaling pathway [38]. GCSF activates STAT proteins and the PI3-K/Akt pathway [39]. Results from non-stroke studies indicate that BDNF affects differentiating oligodendrocytes and improves axonal growth and plasticity by increasing the levels of MBP cells and MBP protein and decreasing Nogo-A levels [34].…”

Immunomodulation as Therapy for Fungal Infection: Are We Closer?

“…Granulocyte colony-stimulating factor, generic names include filgrastim and lenograstim, primarily stimulates neutrophil production and maturation. Chemotherapy may be myelosuppressive, causing neutropenia, and G-CSF can be used adjunctly to restore neutrophil counts (reviewed in Wright et al, 2017 ).…”