scholarly journals Beneficial Effect of IL-4 and SDF-1 on Myogenic Potential of Mouse and Human Adipose Tissue-Derived Stromal Cells

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1479
Author(s):  
Karolina Archacka ◽  
Joanna Bem ◽  
Edyta Brzoska ◽  
Areta M. Czerwinska ◽  
Iwona Grabowska ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Satellite Cells ◽  
Stromal Cells ◽  
Muscle Regeneration ◽  
Myogenic Differentiation ◽  
Human Adipose Tissue ◽  
Skeletal Muscle Regeneration ◽  
Animal Cells ◽  
The Impact

Under physiological conditions skeletal muscle regeneration depends on the satellite cells. After injury these cells become activated, proliferate, and differentiate into myofibers reconstructing damaged tissue. Under pathological conditions satellite cells are not sufficient to support regeneration. For this reason, other cells are sought to be used in cell therapies, and different factors are tested as a tool to improve the regenerative potential of such cells. Many studies are conducted using animal cells, omitting the necessity to learn about human cells and compare them to animal ones. Here, we analyze and compare the impact of IL-4 and SDF-1, factors chosen by us on the basis of their ability to support myogenic differentiation and cell migration, at mouse and human adipose tissue-derived stromal cells (ADSCs). Importantly, we documented that mouse and human ADSCs differ in certain reactions to IL-4 and SDF-1. In general, the selected factors impacted transcriptome of ADSCs and improved migration and fusion ability of cells in vitro. In vivo, after transplantation into injured muscles, mouse ADSCs more eagerly participated in new myofiber formation than the human ones. However, regardless of the origin, ADSCs alleviated immune response and supported muscle reconstruction, and cytokine treatment enhanced these effects. Thus, we documented that the presence of ADSCs improves skeletal muscle regeneration and this influence could be increased by cell pretreatment with IL-4 and SDF-1.

scholarly journals The LIM domain protein nTRIP6 modulates the dynamics of myogenic differentiation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tannaz Norizadeh Abbariki ◽  
Zita Gonda ◽  
Denise Kemler ◽  
Pavel Urbanek ◽  
Tabea Wagner ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Myogenic Differentiation ◽  
Skeletal Muscle Regeneration ◽  
Temporal Control ◽  
Lim Domain ◽  
Lim Domain Protein ◽  
Domain Protein

AbstractThe process of myogenesis which operates during skeletal muscle regeneration involves the activation of muscle stem cells, the so-called satellite cells. These then give rise to proliferating progenitors, the myoblasts which subsequently exit the cell cycle and differentiate into committed precursors, the myocytes. Ultimately, the fusion of myocytes leads to myofiber formation. Here we reveal a role for the transcriptional co-regulator nTRIP6, the nuclear isoform of the LIM-domain protein TRIP6, in the temporal control of myogenesis. In an in vitro model of myogenesis, the expression of nTRIP6 is transiently up-regulated at the transition between proliferation and differentiation, whereas that of the cytosolic isoform TRIP6 is not altered. Selectively blocking nTRIP6 function results in accelerated early differentiation followed by deregulated late differentiation and fusion. Thus, the transient increase in nTRIP6 expression appears to prevent premature differentiation. Accordingly, knocking out the Trip6 gene in satellite cells leads to deregulated skeletal muscle regeneration dynamics in the mouse. Thus, dynamic changes in nTRIP6 expression contributes to the temporal control of myogenesis.

scholarly journals Potential Role of Omega-3 Fatty Acids on the Myogenic Program of Satellite Cells

2016 ◽  
Vol 9 ◽  
pp. NMI.S27481 ◽  
Author(s):  
Amritpal S. Bhullar ◽  
Charles T. Putman ◽  
Vera C. Mazurak
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Myogenic Differentiation ◽  
Skeletal Muscle Regeneration ◽  
Stem Cell Population ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Myogenic Program

Skeletal muscle loss is associated with aging as well as pathological conditions. Satellite cells (SCs) play an important role in muscle regeneration. Omega-3 fatty acids are widely studied in a variety of muscle wasting diseases; however, little is known about their impact on skeletal muscle regeneration. The aim of this review is to evaluate studies examining the effect of omega-3 fatty acids, α-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid on the regulation of SC proliferation and differentiation. This review highlights mechanisms by which omega-3 fatty acids may modulate the myogenic program of the stem cell population within skeletal muscles and identifies considerations for future studies. It is proposed that minimally three myogenic transcriptional regulatory factors, paired box 7 (Pax7), myogenic differentiation 1 protein, and myogenin, should be measured to confirm the stage of SCs within the myogenic program affected by omega-3 fatty acids.

Skeletal Muscle Regeneration by the Exosomes of Adipose Tissue-Derived Mesenchymal Stem Cells

2021 ◽  
Vol 43 (3) ◽  
pp. 1473-1488
Author(s):  
Seong-Eun Byun ◽  
Changgon Sim ◽  
Yoonhui Chung ◽  
Hyung Kyung Kim ◽  
Sungmoon Park ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Muscle Regeneration ◽  
Therapeutic Potential ◽  
Human Adipose Tissue ◽  
Treated Group ◽  
Skeletal Muscle Regeneration ◽  
Biopsy Punch ◽  
Healthy Control ◽  
Muscle Defect

Profound skeletal muscle loss can lead to severe disability and cosmetic deformities. Mesenchymal stem cell (MSC)-derived exosomes have shown potential as an effective therapeutic tool for tissue regeneration. This study aimed to determine the regenerative capacity of MSC-derived exosomes for skeletal muscle regeneration. Exosomes were isolated from human adipose tissue-derived MSCs (AD-MSCs). The effects of MSC-derived exosomes on satellite cells were investigated using cell viability, relevant genes, and protein analyses. Moreover, NOD-SCID mice were used and randomly assigned to the healthy control (n = 4), muscle defect (n = 6), and muscle defect + exosome (n = 6) groups. Muscle defects were created using a biopsy punch on the quadriceps of the hind limb. Four weeks after the surgery, the quadriceps muscles were harvested, weighed, and histologically analyzed. MSC-derived exosome treatment increased the proliferation and expression of myocyte-related genes, and immunofluorescence analysis for myogenin revealed a similar trend. Histologically, MSC-derived exosome-treated mice showed relatively preserved shapes and sizes of the muscle bundles. Immunohistochemical staining revealed greater expression of myogenin and myoblast determination protein 1 in the MSC-derived exosome-treated group. These results indicate that exosomes extracted from AD-MSCs have the therapeutic potential for skeletal muscle regeneration.

scholarly journals Disease-associated metabolic alterations that impact satellite cells and muscle regeneration: perspectives and therapeutic outlook

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Josiane Joseph ◽  
Jason D. Doles
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Cell Activity ◽  
Skeletal Muscle Regeneration ◽  
Metabolic Alterations ◽  
Skeletal Muscle Wasting ◽  
Patients Experience ◽  
The Impact

AbstractMany chronic disease patients experience a concurrent loss of lean muscle mass. Skeletal muscle is a dynamic tissue maintained by continuous protein turnover and progenitor cell activity. Muscle stem cells, or satellite cells, differentiate (by a process called myogenesis) and fuse to repair and regenerate muscle. During myogenesis, satellite cells undergo extensive metabolic alterations; therefore, pathologies characterized by metabolic derangements have the potential to impair myogenesis, and consequently exacerbate skeletal muscle wasting. How disease-associated metabolic disruptions in satellite cells might be contributing to wasting is an important question that is largely neglected. With this review we highlight the impact of various metabolic disruptions in disease on myogenesis and skeletal muscle regeneration. We also discuss metabolic therapies with the potential to improve myogenesis, skeletal muscle regeneration, and ultimately muscle mass.

scholarly journals OR01-03 Thyroid Receptor Alpha Interacts with COUP-TFII in the Regulation of Postnatal Skeletal Muscle Regeneration

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Paola Aguiari ◽  
Astgik Petrosyan ◽  
Yan-Yun Liu ◽  
Sheue-Yann Cheng ◽  
Laura Perin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Thyroid Hormone ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Myogenic Differentiation ◽  
Orphan Receptor ◽  
Skeletal Muscle Regeneration ◽  
Myoblast Differentiation ◽  
Hormone Signaling

Abstract Myopathic changes, including muscular dystrophy and weakness, are commonly described in hypothyroid and hyperthyroid patients. Thyroid hormone signaling, via activation of thyroid nuclear receptors (TRs), plays an essential role in the maintenance of muscle mass, function, and regeneration. TRs are ligand-inducible transcription factors expressed in almost all tissues, including skeletal muscle. In a mouse model of Resistance to Thyroid Hormone carrying a frame-shift mutation in the TRα gene (TRα1PV)1,2 we observed skeletal muscle loss with aging and impaired skeletal muscle regeneration after injury. We recently described that TRα interacts with the nuclear orphan receptor Chicken Ovalbumin Upstream Promoter-factor II (COUP-TFII, or NR2F2), which is known to regulate myogenesis negatively and has a role in Duchenne-like Muscular Dystrophies3. We showed that COUP-TFII expression declines with age in WT mice, while the skeletal muscle of TRα1PV mice shows a sustained significantly higher expression of COUP-TFII. Our findings suggest that the TRα/COUP-TFII interaction might mediate the impaired skeletal muscle phenotype observed in TRα1PV mice. To better characterize this interaction, we isolated SC from 10 months old WT and TRα1PV mice and cultured them in vitro using novel methods established within our lab. Using siRNA probes, we next silenced COUP-TFII and characterized the cells via RNA-seq analysis. In vitro, we assessed myoblast differentiation and proliferation using differentiation assays and EdU incorporation. We observed that satellite cells from TRα1PV mice display impaired myoblast proliferation and in vitro myogenic differentiation compared to WT SCs. However, when COUP-TFII was silenced, the myogenic potential of TRα1PV satellite cells was restored, with a higher proliferation of myoblasts and a higher number of fully differentiated myotubes after 4 days of myogenic induction. RNAseq analysis on satellite cells from TRα1PV mice after COUP-TFII knockdown showed upregulation of genes involved in the myogenic pathway, such as Myod1 and Pax7, and of genes in the thyroid hormone signaling, such as Dio2. Ingenuity Pathway Analysis further showed activation of pathways regarding cell growth, differentiation, matrix remodeling along with muscle function, muscle contractility, and muscle contraction. These in vitro results suggest that by silencing COUP-TFII we promote the myogenic pathway and may further rescue the impaired phenotype of TRα1PV mice. These studies can help increase our knowledge of the mechanisms involved in thyroid hormone signaling in skeletal muscle regeneration, which will ultimately increase the possibility of designing more specific treatments for patients with thyroid hormone-induced myopathies. References: 1Milanesi, A., et al, Endocrinology 2016; 2Kaneshige, M. et al, Proc Natl Acad Sci U S 2001; 3Lee HJ, et al, Sci Rep. 2017.

scholarly journals Adipose Tissue-Derived Stromal Cells in Matrigel Impact the Regeneration of Severely Damaged Skeletal Muscles

2019 ◽  
Vol 20 (13) ◽  
pp. 3313 ◽  
Author(s):  
Iwona Grabowska ◽  
Malgorzata Zimowska ◽  
Karolina Maciejewska ◽  
Zuzanna Jablonska ◽  
Anna Bazga ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Muscle Mass ◽  
Stromal Cells ◽  
Muscle Regeneration ◽  
Skeletal Muscles ◽  
Skeletal Muscle Regeneration ◽  
Severely Injured ◽  
Different Types ◽  
Gastrocnemius Muscles ◽  
The Impact

In case of large injuries of skeletal muscles the pool of endogenous stem cells, i.e., satellite cells, might be not sufficient to secure proper regeneration. Such failure in reconstruction is often associated with loss of muscle mass and excessive formation of connective tissue. Therapies aiming to improve skeletal muscle regeneration and prevent fibrosis may rely on the transplantation of different types of stem cell. Among such cells are adipose tissue-derived stromal cells (ADSCs) which are relatively easy to isolate, culture, and manipulate. Our study aimed to verify applicability of ADSCs in the therapies of severely injured skeletal muscles. We tested whether 3D structures obtained from Matrigel populated with ADSCs and transplanted to regenerating mouse gastrocnemius muscles could improve the regeneration. In addition, ADSCs used in this study were pretreated with myoblasts-conditioned medium or anti-TGFβ antibody, i.e., the factors modifying their ability to proliferate, migrate, or differentiate. Analyses performed one week after injury allowed us to show the impact of 3D cultured control and pretreated ADSCs at muscle mass and structure, as well as fibrosis development immune response of the injured muscle.

scholarly journals Hypoxia preconditioned bone marrow-derived mesenchymal stromal/stem cells enhance myoblast fusion and skeletal muscle regeneration

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Karolina Archacka ◽  
Iwona Grabowska ◽  
Bartosz Mierzejewski ◽  
Joanna Graffstein ◽  
Alicja Górzyńska ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Bone Marrow ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Myogenic Differentiation ◽  
Skeletal Muscle Regeneration ◽  
Hypoxic Conditions ◽  
Cell Engraftment

Abstract Background The skeletal muscle reconstruction occurs thanks to unipotent stem cells, i.e., satellite cells. The satellite cells remain quiescent and localized between myofiber sarcolemma and basal lamina. They are activated in response to muscle injury, proliferate, differentiate into myoblasts, and recreate myofibers. The stem and progenitor cells support skeletal muscle regeneration, which could be disturbed by extensive damage, sarcopenia, cachexia, or genetic diseases like dystrophy. Many lines of evidence showed that the level of oxygen regulates the course of cell proliferation and differentiation. Methods In the present study, we analyzed hypoxia impact on human and pig bone marrow-derived mesenchymal stromal cell (MSC) and mouse myoblast proliferation, differentiation, and fusion. Moreover, the influence of the transplantation of human bone marrow-derived MSCs cultured under hypoxic conditions on skeletal muscle regeneration was studied. Results We showed that bone marrow-derived MSCs increased VEGF expression and improved myogenesis under hypoxic conditions in vitro. Transplantation of hypoxia preconditioned bone marrow-derived MSCs into injured muscles resulted in the improved cell engraftment and formation of new vessels. Conclusions We suggested that SDF-1 and VEGF secreted by hypoxia preconditioned bone marrow-derived MSCs played an essential role in cell engraftment and angiogenesis. Importantly, hypoxia preconditioned bone marrow-derived MSCs more efficiently engrafted injured muscles; however, they did not undergo myogenic differentiation.

scholarly journals Loss of the adipokine lipocalin-2 impairs satellite cell activation and skeletal muscle regeneration

2018 ◽  
Vol 315 (5) ◽  
pp. C714-C721 ◽  
Author(s):  
Irena A. Rebalka ◽  
Cynthia M. F. Monaco ◽  
Nina E. Varah ◽  
Thorsten Berger ◽  
Donna M. D’souza ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Cell Activation ◽  
Skeletal Muscle Regeneration ◽  
Matrix Remodeling ◽  
Muscle Repair ◽  
Lipocalin 2 ◽  
The Impact

Lipocalin-2 (LCN2) is an adipokine previously described for its contribution to numerous processes, including innate immunity and energy metabolism. LCN2 has also been demonstrated to be an extracellular matrix (ECM) regulator through its association with the ECM protease matrix metalloproteinase-9 (MMP-9). With the global rise in obesity and the associated comorbidities related to increasing adiposity, it is imperative to gain an understanding of the cross talk between adipose tissue and other metabolic tissues, such as skeletal muscle. Given the function of LCN2 on the ECM in other tissues and the importance of matrix remodeling in skeletal muscle regeneration, we examined the localization and expression of LCN2 in uninjured and regenerating wild-type skeletal muscle and assessed the impact of LCN2 deletion (LCN2−/−) on skeletal muscle repair following cardiotoxin injury. Though LCN2 was minimally present in uninjured skeletal muscle, its expression was increased significantly at 1 and 2 days postinjury, with expression present in Pax7-positive satellite cells. Although satellite cell content was unchanged, the ability of quiescent satellite cells to become activated was significantly impaired in LCN2−/− skeletal muscles. Skeletal muscle regeneration was also significantly compromised as evidenced by decreased embryonic myosin heavy chain expression and smaller regenerating myofiber areas. Consistent with a role for LCN2 in MMP-9 regulation, regenerating muscle also displayed a significant increase in fibrosis and lower ( P = 0.07) MMP-9 activity in LCN2−/− mice at 2 days postinjury. These data highlight a novel role for LCN2 in muscle regeneration and suggest that changes in adipokine expression can significantly impact skeletal muscle repair.

scholarly journals Hypoxic Preconditioned Bone Marrow-Derived Mesenchymal Stromal/Stem Cells Enhance Myoblast Fusion and Skeletal Muscle Regeneration

2021 ◽  
Author(s):  
Karolina Archacka ◽  
Iwona Grabowska ◽  
Bartosz Mierzejewski ◽  
Joanna Graffstain ◽  
Alicja Górzyńska ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Bone Marrow ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Myogenic Differentiation ◽  
Skeletal Muscle Regeneration ◽  
Hypoxic Conditions ◽  
Cell Engraftment

Abstract Background: The skeletal muscle reconstruction occurs thanks to unipotent stem cells, i.e., satellite cells. The satellite cells remain quiescent and localized between myofiber sarcolemma and basal lamina. They are activated in response to muscle injury, proliferate, differentiate into myoblasts, and recreate myofibers. Many stem and progenitor cells support skeletal muscle regeneration, which could be disturbed by extensive damage, sarcopenia, cachexia, or genetic diseases like dystrophy. Many lines of evidence showed that the level of oxygen regulates the course of cell proliferation and differentiation. Methods: In the present study, we analyzed hypoxic’s impact on human and pig bone marrow-derived mesenchymal stromal cell (MSC) and mouse myoblast proliferation, differentiation, and fusion. Moreover, the influence of the transplantation of human bone marrow-derived MSCs cultured under hypoxic conditions on skeletal muscle regeneration was studied. Results: We showed that bone marrow-derived MSCs increased VEGF expression and improved myogenesis under hypoxic conditions in vitro. Transplantation of hypoxic preconditioned bone marrow-derived MSCs into injured muscles resulted in the improved cell engraftment and formation of new vessels. Conclusions: We suggested that SDF-1 and VEGF secreted by hypoxic preconditioned bone marrow-derived MSCs played an essential role in cell engraftment and angiogenesis. Importantly, hypoxic preconditioned bone marrow-derived MSCs more efficiently engrafted injured muscles, however, they did not undergo myogenic differentiation.

Molecular Basis of Skeletal Muscle Regeneration

1996 ◽  
Vol 21 (3) ◽  
pp. 155-184 ◽  
Author(s):  
Rebecca L. Chambers ◽  
John C. McDermott
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factors ◽  
Growth Factors ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Myogenic Differentiation ◽  
Skeletal Muscle Regeneration ◽  
Regulatory Sequences ◽  
Nuclear Factors ◽  
Dna Regulatory Sequences

Skeletal muscle regeneration is a vital process with important implications for various muscle myopathies and adaptations to physiological overload. Few of the molecular regulatory proteins controlling this process have so far been identified. Several growth factors have defined effects on myogenic precursor cells and appear to also be involved during regeneration. In addition, factors that may be released by cells of the immune system may activate satellite cells during regeneration. Many of these growth factors are associated with signalling cascades which transmit information to the nucleus. The nuclear "receptors" that receive the incoming signals are transcription factors that interact with DNA regulatory sequences in order to modulate gene expression. Of the nuclear factors isolated so far, the immediate-early genes are associated with muscle precursor cell proliferation. This review aims to synthesize the extensive research on myogenic differentiation and relate this to research concerning the molecular regulation of skeletal muscle regeneration. Key words: satellite cells, growth factors, signal transduction, transcription factors, gene regulation, overload adaptation

Sign in / Sign up

Export Citation Format

Share Document