Mechanism of satellite cell regulation and its role in ecological niche signaling during skeletal muscle regeneration / 中国组织工程研究

BACKGROUND:Satellite cells are a specific population of adult stem cells contained in skeletal muscle that promote the regenerative reconstruction of injured skeletal muscle,but their specific mechanisms are not well established. OBJECTIVE:To review the regulatory role of satellite cells during skeletal muscle regeneration and the mechanism of interaction between satellite cells and their ecological niche signals,aiming to provide new research ideas and perspectives based on the summary of existing knowledge. METHODS:Web of Science,PubMed,CNKI,WanFang,and VIP databases were searched for literature published between January 2002 and June 2022.English search terms were"muscle,skeletal muscle,muscle injury,stem cells,satellite cells,muscle repair".Chinese search terms were"skeletal muscle,skeletal muscle regeneration,skeletal muscle reconstruction,satellite cells,ecological niche".The 66 included papers were organized and analyzed. RESULTS AND CONCLUSION:(1)Satellite cells exist in skeletal muscle and contribute to both the formation of new muscle fibers after injury and the effective growth of existing adult muscle fibers.(2)After the activation of quiescent satellite cells in satellite cells,the steps of satellite cell proliferation,differentiation and fusion to form muscle fibers during skeletal muscle regeneration are influenced by their intrinsic regulatory effects of different mechanisms.(3)Satellite cells can interact with myofibers,extracellular matrix,skeletal muscle junctions,fibroblast progenitor cells,immune cells and endothelial cells in the ecological niche signal to promote satellite cell activation,proliferation and differentiation to achieve effective skeletal muscle regeneration.(4)Possible breakthroughs in future research include:the division pattern of satellite cells in the body;the mechanisms regulating satellite cell transfer;the specific timing of satellite cell differentiation or self-renewal in vivo;and the interaction mechanisms between satellite cells and skeletal muscle junctions.(5)This review may provide some theoretical reference values for the field of injury reconstruction of skeletal muscle and its innovation.

Biological mechanism of satellite cell aging in skeletal muscles and potential coping strategies / 中国组织工程研究

BACKGROUND:Satellite cells are myogenic stem cells located between the muscle fiber membrane and the basement membrane.However,a comprehensive review of the aging mechanisms of satellite cells and their potential mitigation strategies is still lacking.This gap in knowledge hinders the effective guidance for current strategies aimed at attenuating skeletal muscle aging. OBJECTIVE:To review the mechanisms of satellite cell aging in skeletal muscle and the relevant strategies for mitigating this aging process. METHODS:Major databases were searched up to May 2023,including Web of Science,PubMed,China National Knowledge Infrastructure(CNKI),WanFang Data,and VIP.Chinese and English search terms included"skeletal muscle,satellite cells,aging,mechanism,and solution strategy".After strict inclusion and exclusion criteria were applied,78 articles were finally included. RESULTS AND CONCLUSION:(1)Satellite cells,situated between the muscle fiber membrane and basement membrane,possess proliferative and differentiative potential.They usually remain in a quiescent state but become activated in response to muscle tissue stimuli,participating in processes of repair and restoration of normal tissue structure.Aging leads to a reduction in satellite cell numbers,resulting in symptoms such as muscle weakness and decreased endurance.(2)Mechanisms of satellite cell aging primarily involve diminished regenerative capacity,perturbed niche interactions with changing ecology,age-dependent loss,and heterogeneity changes.Reduced satellite cell numbers and activity due to aging lead to slower muscle regeneration and increased injury recovery time.Errors during differentiation may occur,resulting in decreased muscle quality and function deterioration.(3)Strategies for mitigating satellite cell aging encompass modulation of the receptor environment of intra-body satellite cells,peripheral interventions to promote satellite cell regeneration,construction of human muscle models,and exercise and nutritional interventions to induce satellite cell proliferation.These strategies hold promise in offering novel insights and methods for satellite cell regeneration and treatment of skeletal muscle diseases.(4)Future research should delve into the mechanisms of satellite cell aging,explore the interaction between satellite cells and their niches,investigate the relationship of satellite cells with the immune system and mitochondrial function,and develop human muscle models to enhance research depth and accuracy.

Effects of electroacupuncture on gait and proliferation and differentiation of muscle satellite cell in rats with acute blunt trauma of gastrocnemius muscle / 中国针灸

OBJECTIVE@#To observe the effects of electroacupuncture on threshold of pain, gait, proliferation and differentiation of muscle satellite cell in rats with acute blunt trauma of gastrocnemius muscle, and to explore the possible mechanism of electroacupuncture in promoting the repair of acute injury of skeletal muscle.@*METHODS@#A total of 48 SD rats were randomly divided into a blank group (6 rats), a model group (24 rats) and an electroacupuncture group (18 rats). In the model group and the electroacupuncture group, the model of acute blunt trauma of gastrocnemius muscle was established by self-made impactor. In the electroacupuncture group, electroacupuncture was applied at "Chengshan" (BL 57) and "Yanglingquan" (GB 34) on the right side, with disperse-dense wave, in frequency of 2 Hz/100 Hz, once a day, 30 min each time. Electroacupuncture intervention was performed for 3, 7 and 14 days according to the sampling time. On the 1st, 3rd, 7th and 14th days after modeling, the mechanical withdrawal pain threshold of hindfoot was detected by Von Frey method; the standing time and the maximum contact area of the right hindfoot were recorded by Cat Walk XTTM animal gait analysis instrument; the morphology of the right gastrocnemius muscle and the number of inflammatory cells were observed by HE staining; the positive expression of paired box gene 7 (Pax7) and myogenic differentiation (MyoD) of the right gastrocnemius muscle was detected by immunofluorescence.@*RESULTS@#After modeling, the muscle fiber rupture and massive infiltration of red blood cells and inflammatory cells were observed in the right gastrocnemius muscle; after electroacupuncture intervention, the morphology of muscle fiber was intact and the infiltration of inflammatory cells was improved. Compared with the blank group, in the model group, the differences of mechanical withdrawal pain threshold between the left and right foot were increased (P<0.05), the standing time was shortened and the maximum contact area of the right hindfoot was decreased (P<0.05), the number of inflammatory cells and the positive expression of Pax7 and MyoD of the right gastrocnemius muscle were increased (P<0.05) on the 1st, 3rd, 7th and 14th days after modeling. Compared with the model group, in the electroacupuncture group, the differences of mechanical withdrawal pain threshold were decreased (P<0.05), the standing time was prolonged (P<0.05), the number of inflammatory cells of right gastrocnemius muscle was decreased (P<0.05) on the 7th and 14th days after modeling; the maximum contact area of the right hindfoot was increased (P<0.05), the positive expression of MyoD of the right gastrocnemius muscle was increased (P<0.05) on the 3rd, 7th and 14th days after modeling; the positive expression of Pax7 of the right gastrocnemius muscle was increased (P<0.05) on the 3rd day after modeling.@*CONCLUSION@#Electroacupuncture can effectively improve the pain threshold and gait in rats with acute blunt trauma of gastrocnemius muscle, and promote the repair of skeletal muscle injury, the mechanism may be related to the up-regulation of Pax7 and MyoD, so as to promoting the proliferation and differentiation of muscle satellite cell.

Nerve growth factor interferes with proliferation and alpha-actin expression of skeletal muscle satellite cells in rats / 中国组织工程研究

BACKGROUND: Clinical studies have confirmed that the injection of nerve growth factor into the nerve damage site can improve the motor function of skeletal muscle. OBJECTIVE: To observe the effect of nerve growth factor on the proliferation of primary skeletal muscle satellite cells in rats. METHODS: The original generation of rat skeletal muscle satellite cells were cultivated by the tissue block method, and the third generation of skeletal muscle satellite cells were divided into three groups. The control group was added with culture medium; the low concentration group and the high concentration group were added with culture medium containing 10, 20 U/mL nerve growth factors, respectively. At 2, 4 and 6 days after culture, the cell morphology was observed by inverted phase contrast microscope and hematoxylin-eosin staining, and the expression of α-actin was observed by immunohistochemistry. At 1, 2, 3, and 4 days after culture, CCK-8 assay was used to detect the cell proliferation activity. RESULTS AND CONCLUSION: (1) Inverted phase contrast microscope displayed that with the increase of culture time, the number of skeletal muscle satellite cells in each group increased gradually, and the cell morphology gradually changed from round to fusiform, spindle or polygonal, and gradually fused and arranged along the same direction, and the number of cells in high concentration group was more than that in low concentration group and control group (P 0.05). (4) The CCK-8 assay results showed that cell viability of low and high concentration groups was higher than that of control group (P=0.000). (5) Above results confirm that high and low concentrations of nerve growth factors could promote the proliferation of skeletal muscle satellite cells, but had no effect on the expression of α-actin in skeletal muscle satellite cells.

Effects of hypoxia exposure on skeletal muscle in vivo / 体力科学

Hypoxic condition of skeletal muscle is caused not only by hypoxia exposure but also by exercise and disease etc. It is thought that clarifying a mechanism of response to hypoxia in vivo is useful for developing better training methods and treatment strategies. However, at present, research dealing with the effects of hypoxic exposure on skeletal muscle have not shown consistent results. Hypoxic exposure results in angiogenesis or muscle atrophy as morphological changes in skeletal muscle. Applications of hypoxic exposure include intermittent hypoxic exposure and hypoxic training, both of which may lead to angiogenesis in a mechanism different from normal hypoxic exposure. In this review, we present some findings on the effects of hypoxia exposure on skeletal muscle and discuss whether satellite cells are involved in promoting angiogenesis by hypoxia.

MBP-FGF2-Immobilized Matrix Maintains Self-Renewal and Myogenic Differentiation Potential of Skeletal Muscle Stem Cells

The robust capacity of skeletal muscle stem cells (SkMSCs, or satellite cells) to regenerate into new muscles in vivo has offered promising therapeutic options for the treatment of degenerative muscle diseases. However, the practical use of SkMSCs to treat muscle diseases is limited, owing to their inability to expand in vitro under defined cultivation conditions without loss of engraftment efficiency. To develop an optimal cultivation condition for SkMSCs, we investigated the behavior of SkMSCs on synthetic maltose-binding protein (MBP)-fibroblast growth factor 2 (FGF2)-immobilized matrix in vitro. We found that the chemically well-defined, xeno-free MBP-FGF2-immobilized matrix effectively supports SkMSC growth without reducing their differentiation potential in vitro. Our data highlights the possible application of the MBP-FGF2 matrix for SkMSC expansion in vitro.

Effect of electroacupuncture on muscular atrophy and expression of microRNAs and muscle satellite cell proliferation related proteins in denervated gastrocnemius muscle rats / 针刺研究

OBJECTIVE: To investigate the effect of electroacupuncture (EA) on muscular atrophy and expression of microRNAs (Mir-1, Mir-133a, Mir-133b) and some proliferation-related factors of muscle satellite cells as histone deacetylase4 (HDAC4) and the paired box transcription factor Pax7 (Pax7) in skeletal muscle atrophy rats. METHODS: Twenty-four male SD rats were randomly and equally divided into sham operation, model and EA groups. The skeletal muscle atrophy model was established by transection of the right sciatic nerve. EA (2 Hz, 1 mA) was applied to the right "Zusanli"(ST36) and "Huantiao"(GB30) for 10 min, once a day, seven times a week for 2 weeks. The wet weight of bilateral gastrocnemius muscles was measured to calculate the ratio of weight between the affected gastrocnemius muscle and healthy gastrocnemius muscle. The cross-sectional area (CSA) of the gastrocnemius muscle on the affected side was measured after H.E. staining. The expression levels of Mir-1, Mir-133a, Mir-133b, HDAC4 mRNA and Pax7 mRNA in the gastrocnemius muscle tissue were detected using quantitative real time-PCR. RESULTS: Compared with the sham operation group, the ratio of wet weight and CSA of the gastrocnemius muscle, and the expression levels of Mir-1 and Mir-133a were significantly decreased in the model group (P<0.01, P<0.05), while the expression levels of HDAC4 mRNA and Mir-133b significantly up-regulated in the model group (P<0.05). Following EA intervention, the decreased levels of the ratio of wet weight and CSA of the gastrocnemius muscle were significantly suppressed (P<0.01), suggesting an inhibition of the skeletal muscle atrophy, and the expression levels of Pax7 and HDAC4 mRNAs were notably up-regulated (P<0.05), and those of Mir-1, Mir-133a and Mir-133b were significantly or further significantly down-regulated relevant to the model group (P<0.05). CONCLUSION: EA intervention can delay muscular atrophy in rats with denervated gastrocnemius muscle, which may be related with its function in up-regulating the expression of Pax7 and HDAC4 mRNAs and down-regulating the expression of Mir-1, Mir-133a and Mir-133b.

Effect of a combination of astaxanthin supplementation, heat stress, and intermittent reloading on satellite cells during disuse muscle atrophy / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

We examined the effect of a combination of astaxanthin (AX) supplementation, repeated heat stress, and intermittent reloading (IR) on satellite cells in unloaded rat soleus muscles. Forty-nine male Wistar rats (8-week-old) were divided into control, hind-limb unweighting (HU), IR during HU, IR with AX supplementation, IR with repeated heat stress (41.0-41.5 °C for 30 min), and IR with AX supplementation and repeated heat stress groups. After the experimental period, the antigravitational soleus muscle was analyzed using an immunohistochemical technique. Our results revealed that the combination of dietary AX supplementation and heat stress resulted in protection against disuse muscle atrophy in the soleus muscle. This protective effect may be partially due to a higher satellite cell number in the atrophied soleus muscle in the IR/AX/heat stress group compared with the numbers found in the other groups. We concluded that the combination treatment with dietary AX supplementation and repeated heat stress attenuates soleus muscle atrophy, in part by increasing the number of satellite cells.

Modes of muscle satellite cells fusing myotubes of spontaneous contraction in vitro / 中华地方病学杂志

Objective To investigate the cell-fusion modes and contractive characteristics of myotubes formed by muscle satellite cells in vitro. Methods The muscle satellite cells in quadriceps femoris of six 2-day-old SD rats were isolated, cultured and identified by immunofluorescence; the cell-fusion modes and contractive characteristics of myotubes were observed and recorded under microscope. Results The positve cells expressing marker Pax7 were obtained by immunofluorescence, and the purity was 90.3%. Myotubes were fused by several cells, cell and myotube or myotube and myotube. There were myotubes of spontaneous contraction on the conditions of no acetylcholine, no electric stimulation or no contiguous cells. Conclusion The myotubes of spontaneous contraction are fused by muscle satellite cells through three cell-fusion modes in vitro.

Effects of Electroacupuncture on Insulin-like Growth Factor-1, Myostatin and Satellite-cell Proliferation in Rats with Denervated Skeletal Muscle Atrophy / 中国康复理论与实践

@#Objective To observe effects and mechanism of electroacupuncture (EA) on denervated skeletal muscle atrophy. Methods Forty-nine male Sprague-Dawley rats were randomly divided into normal group (group A, n=7), natural recovery group (group B, n=21) and EA group (group C, n=21). The groups B and C, established the model of denervated skeletal muscle atrophy by transecting the sciatic nerve of rats, were divided into subgroups of 7 days, 14 days, 21 days postoperation, seven in each subgroup. Electroacupuncture was given to the group C at Zusanli (ST36) and Chengshan (BL57) once a day since 24 hours after modeling. The muscle wet weight ratio of the affected gastrocnemius was determined. Cross-sectional area and fiber diameter of the gastrocnemius were measured with HE staining. The expression of insulin-like growth factor-1 (IGF-1), Myostatin and proliferating cell nuclear antigen (PCNA) protein and gene in the gastrocnemius were detected with Western blotting and RT-PCR. Results The wet weight ratio, cross-sectional area and fiber diameter were less in the groups B and C than in the group A (P<0.001), and they were more in the group C than in the group B (P<0.001). Compared with the group B, the protein and gene of IGF-1, PCNA increased in the group C (P<0.05), while the Myostatin decreased (P<0.05). Conclusion Electroacupuncture can increase the expression of IGF-1 and decrease the expression of Myostatin, to promote the proliferation of satellite cell, which may relate with the prevention of denervated skeletal muscle atrophy.

Fibrosis in Skeletal Muscle: Celluar and Molecular Mechanism (review) / 中国康复理论与实践

@#Skeletal muscle has high regenerative capability. It is able to regenerate completely after acute traumatic damage, while the repairing process often accompanied by fibrosis in the chronic degenerative conditions such as muscular dystrophy and repeated muscle fiber damage. Through in-depth study on the mechanisms of skeletal muscle fibrosis in the past decade, it has been found that a variety of cells and regulatory molecules involved in the process, especially muscle satellite cells-derived myofibroblasts, transforming growth factor β (TGF-β) and other fibrosis promoting growth factors. This review focused on the cellular and molecular mechanisms of the skeletal muscle fibrosis and relevant antagonistic strategies.

A stereological analysis of ginsenoside Rg1 in inhibiting hepatic fibrosis / 重庆医学

Objective To investigate the effect of Panax notoginsenosides monomers ginsenoside Rg 1 in inhibiting hepatic fibro-sis .Methods The rat model of hepatic fibrosis was established by using 50% Ccl4 ,total 35 d .The different doses of Rg1was ad-ministered by hypodermical injection .At the end of the treatment ,the pathological changes of hepatic tissue were observed by light and transmission electron microscope .The stereological method was adopted to measure the volume density (Vvm) ,area density (Svm) ,specific surface(Qm) and surface number density (Nam) of liver cell mitochondria in various groups .Results The stereo-logical data of liver cell mitochondria showed that the statistical differences existed among various groups .Vvm in the Panax Notog-insenosides ,low dose Rg1 and isotonic saline groups were significantly increased compared with the normal control group with sta-tistical difference(P0 .05);Vvm in the high ,middle and low dose Rg1 ,Panax No-toginsenosides and colchicine groups showed the decreasing trend compared with the isotonic saline group without statistical differ-ence(P>0 .05) .Svm in the low dose Rg1 ,Panax Notoginsenosides ,colchicine and isotonic saline groups were significantly increased compared with the normal group with statistical difference (P0 .05) .Conclu-sion Rg1 has antifibrosis effects of Panax notoginsenosides ,even exceeds Panax notoginsenosides in some aspects ,and the above-mentioned effect is positively correlated with dose .Rg1 is an ideal drug for preventing and treating liver fibrosis .

Fibrosis in Skeletal Muscle:Celluar and Molecular Mechanism (review) / 中国康复理论与实践

Skeletal muscle has high regenerative capability. It is able to regenerate completely after acute traumatic damage, while the repairing process often accompanied by fibrosis in the chronic degenerative conditions such as muscular dystrophy and repeated muscle fi-ber damage. Through in-depth study on the mechanisms of skeletal muscle fibrosis in the past decade, it has been found that a variety of cells and regulatory molecules involved in the process, especially muscle satellite cells-derived myofibroblasts, transforming growth factor β(TGF-β) and other fibrosis promoting growth factors. This review focused on the cellular and molecular mechanisms of the skeletal muscle fibrosis and relevant antagonistic strategies.

Training and Detraining Effects on Satellite Cell Response after Exhaustive Exercise in Thoroughbred Horses / 体力科学

We investigate the effects of training and detraining on the satellite cell activation in thoroughbred horse muscles after an exhaustive exercise. Six horses were subjected to conventional training for 18 weeks and detraining for 6 weeks. Before training (Pre), after 10-week and 18-week training (10Tr and 18Tr), and after 6-week detraining (DTr), an incremental exercise test (IET) was performed on inclined treadmill to measure VO₂max and the velocity at a plasma lactate of 4 mmol/l (VLA4). Biopsy samples from gluteus medius muscle was obtained before and at 1 minute (1min), 3 hour (3hr), 6 hour (6hr) and 1 day after each IET. Number of muscle satellite cell were counted in type identified muscle fibers by immuno-histochemical stain images. The levels of mRNA expressions were determined using real time RT-PCR system. The number of satellite cells in 10Tr was significantly higher in type IIa fibers (0.31±0.10) than Pre (0.15±0.06). As compared to each value before IET, IL-6 mRNA expression (fold change) increased remarkably at 6hr after IET in 10Tr (x 2290.2) and 18Tr (x 2304.2), but not in both Pre (x 260.0) and DTr (x 853.3). IGF-I and Myogenin mRNA expressions were significantly increased at 1 day after IET in 18Tr (x 6.6 and x 3.3), but not in both Pre and DTr. These results suggested that the increased reactivity of satellite cells by training for 18 weeks is almost disappeared after detraining for 6 week, as well as VO₂max and VLA4.

Plasticity of skeletal muscle and variability of myonuclear domain / 体力科学

Skeletal muscle fiber has a great ability to hypertrophy during growth and in response to exercise stimuli, and atrophy during aging and in response to disuse. Because the muscle fiber is a multinucleated cell, the region of cytoplasm governed by a single myonucleus (myonuclear domain; MND) is a very important factor for understanding muscle plasticity. Although the MND size varies with fiber type, metabolic property and species, it was considered that the size was maintained constantly during muscle adaptation. Recently, however, there have been many studies demonstrating the variability of the MND size. In some of these studies, it is hypothesized that muscle hypertrophy is achieved by increase in protein synthesis rate until the ‘ceiling’ of MND size and subsequent addition of myonuclei by satellite cell activation. On the other hand, during muscle atrophy, the myonuclei seems to be long lasting as ‘muscle memory’ storing information about previous size to prepare for recovery of muscle fiber. Understanding the variability of MND size more deeply would provide fundamental insights into the mechanism of skeletal muscle plasticity.

Bex1 Participates in Muscle Regeneration by Regulating Myogenic Satellite Cell Differentiation / 한국실험동물학회지

Bex1 protein is upregulated in regenerating muscle and interacts with calmodulin, a Ca2+-binding protein involved in cell cycle regulation. Following cardiotoxin-induced injury the regenerating muscle of Bex1 knock-out mice exhibits prolonged cell proliferation and delayed cell differentiation compared to wild-type mice. To gain insight into this process, we compared the regenerating myogenic morphologies of Bex1 knock-out and wild-type mice at several time points. Bex1-positive cells were identified by double immunofluorescence staining. These studies demonstrated that a population of cells that are Bex1-positive after injury are c-Met/basal lamina-positive and Mac-1-negative indicating that they are derived from at least a subset of myogenic progenitor/satellite cells but not invading immune cells. In addition, in regenerating muscle, Bex1 co-localizes with calmodulin in the cytoplasm of the late myoblast or early myotube stage of myogenesis. These results suggest that Bex1 participates in muscle regeneration through the regulation of satellite cell proliferation and differentiation by its interaction with calmodulin. Current studies of Bex1 may provide a new molecular tool for the identification of activated satellite cell and open the way to new or improved therapeutic regimens against progressive muscular atrophy.

Bex1 Participates in Muscle Regeneration by Regulating Myogenic Satellite Cell Differentiation / 한국실험동물학회지

Bex1 protein is upregulated in regenerating muscle and interacts with calmodulin, a Ca2+-binding protein involved in cell cycle regulation. Following cardiotoxin-induced injury the regenerating muscle of Bex1 knock-out mice exhibits prolonged cell proliferation and delayed cell differentiation compared to wild-type mice. To gain insight into this process, we compared the regenerating myogenic morphologies of Bex1 knock-out and wild-type mice at several time points. Bex1-positive cells were identified by double immunofluorescence staining. These studies demonstrated that a population of cells that are Bex1-positive after injury are c-Met/basal lamina-positive and Mac-1-negative indicating that they are derived from at least a subset of myogenic progenitor/satellite cells but not invading immune cells. In addition, in regenerating muscle, Bex1 co-localizes with calmodulin in the cytoplasm of the late myoblast or early myotube stage of myogenesis. These results suggest that Bex1 participates in muscle regeneration through the regulation of satellite cell proliferation and differentiation by its interaction with calmodulin. Current studies of Bex1 may provide a new molecular tool for the identification of activated satellite cell and open the way to new or improved therapeutic regimens against progressive muscular atrophy.

Effects of Massage on Satellite Cells of Acute Contusive Skeletal Muscles / 针灸推拿医学（英文版）

Objective: To study the mechanism of Tuina in the treatment of skeletal muscle injury. Methods: Rabbits were heavily beaten at gastrocnemius muscle to make acute contusion model and then treated respectively by early Tuina and routine Tuina. The number of satellite cells of skeletal muscles was observed. Results: The number of the satellite cells continued to grow in both groups, and it began to increase significantly 3-5 days after Tuina treatment. Early Tuina treatment produces larger number of satellite cells than routine Tuina treatment.Conclusion: Early Tuina treatment is helpful to the marked recovery of skeletal muscles by increasing the number of satellite cell.

NOVEL POSSIBILITIES OF SKELETAL MUSCLE HYPERTROPHY MECHANISM / 体力科学

This review explores novel possibilities of skeletal muscle hypertrophy mechanism based on previous studies. Hypertrophy and/or regeneration of skeletal muscles are caused by activation of satellite cells, induced by mechanisms such as growth factors and cytokines. Many unsolved problems, however, yet remain concerning signaling pathways, activated by such substances, and regulation of transcriptional factors and cell cycles.In recent years, possible involvement of not only satellite cells but also tissue-specific stem cells in skeletal muscle hypertrophy has been reported from studies made on stem cell transplantation in muscle regeneration.It has been elucidated that differentiation plasticity of tissue-specific stem cells contributes to hypertrophy and/or regeneration of skeletal muscles. Moreover, satellite cells have come to be regarded as one kind of tissue-specific stem cells, since they have been known to exhibit diversity, by their differentiating into not only skeletal muscle cells but also other tissue cells, as well as self renewal capacity.This review also summarizes findings on signaling pathways based on ligand receptor characterization. Among the various signaling pathways, focus was especially placed on the possibilities of Wnt signaling pathway and Notch signaling pathway on skeletal muscle hypertrophy, indicating that Wnt expression in adult muscle stem cells leads to regulation of skeletal muscle hypertrophy.It has also become evident that Notch signaling pathway is associated with the activation of satellites cells, and that functional decline of such signaling pathway causes a decline in the activation of satellite cells. Such functional decline of Notch signaling pathway has also been revealed as the reason for the decline of regenerative capacity of skeletal muscles due to advancing age. Further discussion on the involvement of Notch signaling pathway in skeletal muscle hypertrophy is made based on these results. As indicated above, the roles of ligands and/or receptors of canonical growth factors, signaling pathways, and transcriptional factors contributing to skeletal muscle hypertrophy were reexamined in this review, after which the contribution of tissue-specific cells to skeletal muscle hypertrophy was discussed based on the results of muscle regeneration studies. Furthermore, focus was centered on Wnt and Notch signaling pathways, both of which are attracting renewed attention, and study was made on the possibility of the involvement of these pathways in skeletal muscle hypertrophy process.

Morphological study on skeletal satellite cell transplantation applied in therapy of myocardial infarction / 基础医学与临床

Objective To find the features of cryo-injured infarcted model and the therapeutic effects of skeletal satellites cells(SCs) on myocardial infarction(MI).Methods SCs were implanted into the center of cryo-injured myocardium.Immunohistochemistry,confocal immunofluorescence double-labelling staining and transmission electron microscopy were used to study the state of SCs.Results After cryo-injured frontal wall of the left ventricle(LV) for approximately(15 s) by aluminium rod with(5 mm) in diameter,it made 43% weight of LV ischemia and 17% weight of LV infarcted.At 2nd week,injured area occured as transmural infarct.After transplantation,the implanted cells survived in large numbers.The transplanted cells proliferated remarkably at early phase and differentiated into many multinuclear myotubes after 2 weeks.Some of them developed into muscle fibers with better sarcomeres,but the gap junction was not formed between implanted cells and cardiac myocytes.Conclusions Cryo-injured infarcted model is a proper model to study myocardial infarction.Skelatal satellite cell transplantation will repair morphological structure partly of myocardial infarction area.