49 research outputs found
Mouse Satellite Cell Isolation and Transplantation
No full text: Satellite cell (SC) transplantation represents a powerful strategy to investigate SC biology during muscle regeneration. We described here a protocol for SC isolation from green fluorescent protein (GFP)-expressing mice and their transplantation into murine muscles. This procedure was originally used to assess the effects of the hormone unacylated ghrelin on muscle regeneration, in particular evaluating how the increase of unacylated ghrelin in the recipient muscle affected the engraftment of donor SCs ( Reano et al., 2017 )
Acylated and unacylated ghrelin administration to blunt muscle wasting
No full textPurpose of review: Muscle wasting is a comorbidity often associated with a wide range of disorders that severely affects patient prognosis and quality of life. Ghrelin, through its receptor GHSR-1a, stimulates appetite and growth hormone (GH) release. Several studies indicate that ghrelin administration is a valid treatment for cachexia because it improves muscle mass and function, likely by restoring a positive energy balance. RECENT FINDINGS: In addition to its GHSR-1a-mediated effects on muscle mass, ghrelin acts directly on skeletal muscle, wherein it exerts a protective activity against muscle wasting. This direct activity is independent of GHSR-1a and is shared by the unacylated form of ghrelin, which does not bind GHSR-1a and is devoid of the effects on appetite and GH release. SUMMARY: Both the acylated and unacylated forms of ghrelin might have therapeutic potential for the treatment of skeletal muscle wasting. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
Ghrelin and unacylated ghrelin inhibit muscle atrophy in C2C12 myotubes through p38 AND mTORC2 pathways without stimulating mTORC1 and protein synthesis
No full textAntifibrotic Activity of Acylated and Unacylated Ghrelin
Get PDFFibrosis can affect almost all tissues and organs, it often represents the terminal stage of chronic diseases, and it is regarded as a major health issue for which efficient therapies are needed. Tissue injury, by inducing necrosis/apoptosis, triggers inflammatory response that, in turn, promotes fibroblast activation and pathological deposition of extracellular matrix. Acylated and unacylated ghrelin are the main products of the ghrelin gene. The acylated form, through its receptor GHSR-1a, stimulates appetite and growth hormone (GH) release. Although unacylated ghrelin does not bind or activate GHSR-1a, it shares with the acylated form several biological activities. Ghrelin peptides exhibit anti-inflammatory, antioxidative, and antiapoptotic activities, suggesting that they might represent an efficient approach to prevent or reduce fibrosis. The aim of this review is to summarize the available evidence regarding the effects of acylated and unacylated ghrelin on different pathologies and experimental models in which fibrosis is a predominant characteristic
Ghrelin: a novel neuromuscular recovery promoting factor?
No full textPromoting neuromuscular recovery after neural injury is a major clinical issue. While techniques for nerve reconstruction are continuously improving and most peripheral nerve lesions can be repaired today, recovery of the lost function is usually unsatisfac- tory. This evidence claims for innovative nonsurgical therapeutic strategies that can implement the outcome after neural repair.
Although no pharmacological approach for improving posttraumatic neuromuscu- lar recovery has still entered clinical practice, various molecules are explored in exper- imental models of neural repair. One of such molecules is the circulating peptide hormone ghrelin. This hormone has proved to have a positive effect on neural repair after central nervous system lesion, and very recently its effectiveness has also been demonstrated in preventing posttraumatic skeletal muscle atrophy. By contrast, no information is still available about its effectiveness on peripheral nerve regeneration although preliminary data from our laboratory suggest that this molecule can have an effect also in promoting axonal regeneration after nerve injury and repair.
Should this be confirmed, ghrelin might represent an ideal candidate as a therapeu- tic agent for improving posttraumatic neuromuscular recovery because of its putative effects at all the various structural levels involved in this regeneration process, namely, the central nervous system, the peripheral nerve, and the target skeletal muscle
Ghrelin
No full textPromoting neuromuscular recovery after neural injury is a major clinical issue. While techniques for nerve reconstruction are continuously improving and most peripheral nerve lesions can be repaired today, recovery of the lost function is usually unsatisfactory. This evidence claims for innovative nonsurgical therapeutic strategies that can implement the outcome after neural repair.Although no pharmacological approach for improving posttraumatic neuromuscular recovery has still entered clinical practice, various molecules are explored in experimental models of neural repair. One of such molecules is the circulating peptide hormone ghrelin. This hormone has proved to have a positive effect on neural repair after central nervous system lesion, and very recently its effectiveness has also been demonstrated in preventing posttraumatic skeletal muscle atrophy. By contrast, no information is still available about its effectiveness on peripheral nerve regeneration although preliminary data from our laboratory suggest that this molecule can have an effect also in promoting axonal regeneration after nerve injury and repair.Should this be confirmed, ghrelin might represent an ideal candidate as a therapeutic agent for improving posttraumatic neuromuscular recovery because of its putative effects at all the various structural levels involved in this regeneration process, namely, the central nervous system, the peripheral nerve, and the target skeletal muscle. © 2013 Elsevier Inc
Opposing effects of 25-hydroxy- and 1α,25-dihydroxy-vitamin D3 on pro-cachectic cytokine- and cancer conditioned medium-induced atrophy in C2C12 myotubes
No full textCholecalciferol (vitamin D3) has a direct protective activity against interleukin 6-induced atrophy in C2C12 myotubes
Get PDFWe previously determined that different vitamin D metabolites can have opposite effects on C2C12 myotubes, depending on the sites of hydroxylation or doses. Specifically, 25(OH)D3 (25VD) has an anti-atrophic activity, 1,25(OH)2D3 induces atrophy, and 24,25(OH)2D3 is anti-atrophic at low concentrations and atrophic at high concentrations. This study aimed to clarify whether cholecalciferol (VD3) too, the non-hydroxylated upstream metabolite, has a direct effect on muscle cells. Assessing the effects of VD3 treatment on mouse C2C12 skeletal muscle myotubes undergoing atrophy induced by interleukin 6 (IL6), we demonstrated that VD3 has a protective action, preserving C2C12 myotubes size, likely through promoting the differentiation and fusion of residual myoblasts and by modulating the IL6-induced autophagic flux. The lack, in C2C12 myotubes, of the hydroxylase transforming VD3 in the anti-atrophic 25VD metabolite suggests that VD3 may have a direct biological activity on the skeletal muscle. Furthermore, we found that the protective action of VD3 depended on VDR, implying that VD3 too might bind to and activate VDR. However, despite the formation of VDR-RXR heterodimers, VD3 effects do not depend on RXR activity. In conclusion, VD3, in addition to its best-known metabolites, may directly impact on skeletal muscle homeostasis
Correction: Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential.
Get PDF[This corrects the article DOI: 10.1371/journal.pone.0137999.]
Human cardiac progenitor spheroids exhibit enhanced engraftment potential
Get PDFA major obstacle to an effective myocardium stem cell therapy has always been the delivery and survival of implanted stem cells in the heart. Better engraftment can be achieved if cells are administered as cell aggregates, which maintain their extra-cellular matrix (ECM). We have generated spheroid aggregates in less than 24 h by seeding human cardiac progenitor cells (hCPCs) onto methylcellulose hydrogel-coated microwells. Cells within spheroids maintained the expression of stemness/mesenchymal and ECM markers, growth factors and their cognate receptors, cardiac commitment factors, and metalloproteases, as detected by immunofluorescence, q-RT-PCR and immunoarray, and expressed a higher, but regulated, telomerase activity. Compared to cells in monolayers, 3D spheroids secreted also bFGF and showed MMP2 activity. When spheroids were seeded on culture plates, the cells quickly migrated, displaying an increased wound healing ability with or without pharmacological modulation, and reached confluence at a higher rate than cells from conventional monolayers. When spheroids were injected in the heart wall of healthy mice, some cells migrated from the spheroids, engrafted, and remained detectable for at least 1 week after transplantation, while, when the same amount of cells was injected as suspension, no cells were detectable three days after injection. Cells from spheroids displayed the same engraftment capability when they were injected in cardiotoxin-injured myocardium. Our study shows that spherical in vivo ready-to-implant scaffold-less aggregates of hCPCs able to engraft also in the hostile environment of an injured myocardium can be produced with an economic, easy and fast protocol
