Human primary muscle stem cells regenerate injured urethral sphincter in athymic rats

Background:The aim of the study was to demonstrate the efficacy of human muscle stem cells(MuSCs)isolated using innovative technology in restoring internal urinary sphincter function in a preclinical animal model.Methods:Colonies of pure human MuSCs were obtained from muscle biopsy speci-mens.Athymic rats were subjected to internal urethral sphincter damage by electro-cauterization.Five days after injury,2×105 muscle stem cells or medium as control were injected into the area of sphincter damage(n=5 in each group).Peak bladder pressure and rise in pressure were chosen as outcome measures.To repeatedly obtain the necessary pressure values,telemetry sensors had been implanted into the rat bladders 10 days prior to injury.Results:There was a highly significant improvement in the ability to build up peak pressure as well as a pressure rise in animals that had received muscle stem cells as compared to control(p=0.007)3 weeks after the cells had been injected.Only mini-mal histologic evidence of scarring was observed in treated rats.Conclusion:Primary human muscle stem cells obtained using innovative technology functionally restore internal urethral sphincter function after injury.Translation into use in clinical settings is foreseeable.

An effective cytokine combination for ex vivo expansion of porcine muscle stem cells

Cultured meat technology is a novel and promising strategy for sustainable and effective meat production.Muscle stem cells are widely used as seed cell populations because of their ease of access and myogenic differentiation potential.However,muscle stem cells are difficult to continuously propagate ex vivo and are heavily dependent upon serum for survival and growth,which impedes their commercial use as a cultured meat source.Herein,we identified an effective four-cytokine combination to promote long-term proliferation of porcine muscle stem cells using a serial elimination screening approach,which was consisted of long chain human insulin growth factor-1,platelet derived growth factor BB,basic fibroblast growth factor,and epidermal growth factor.The expansion of muscle stem cells with the four-cytokine combination achieved a 6.31×107-fold increase in cell number after 28 days of culture with retained cell myogenic differentiation potential,and most importantly,reduced the amount of fetal bovine serum required for cell culture by at least 5%.Furthermore,the four-cytokine combination exerted the pro-proliferative function by activating PI3K/Akt/mTOR and MEK/ERK signaling pathways.This approach provides for a new means by which to industrialize the production of cultured meat.

Function and regulation of muscle stem cells in skeletal muscle development and regeneration:a narrative review

Skeletal muscle plays an essential role in generating the mechanical force necessary to support the movement of our body and daily exercise. Compared with cardiac and smooth muscle, in mammals, skeletal muscle exhibits remarkable regenerative capacity in response to damage. Muscle stem cells, also known as satellite cells, directly contribute to regeneration. Here, we review primary and secondary myogenesis processes with a focus on muscle stem cells, as well as the function and regulation of muscle stem cells in adult muscle regeneration in mammals.

Effect of Sijunzi Decoction on the Myonuclear Domain of Rat Soleus in Spleen Qi Deficiency

Objective: To study the mechanism of Sijunzi decoction treating limb weakness in spleen Qi deficiency (SQD) based on the myonuclear domain (MND) theory. Methods: 40 male Sprague-Dawley rats were randomly divided into the normal group, SQD model group (model group), SQD+ still water group (SW group) and SQD+ Sijunzi decoction group (CM group), 10 rats each group;Grip-Strength Meter was used to measure limb grip strength;transmission electron microscope was employed to observe the ultrastructural changes of the myofibers, Image Pro 6.0 was used to measure the myonuclear numbers, cross-section area (CSA) and then their ratios (the MND sizes) were calculated, immunofluorescence assay was chosen to test the expressions of paired box gene 7 (Pax7) and myogenic differentiation antigen (MyoD). Results: Compared with those in the normal group, limb grip strength was decreased, sarcomeres were abnormal, and all the myonuclear numbers, CSA and MND sizes were reduced, but the Pax7+ cell numbers were increased, significantly, in the model and SW groups;Compared with those in the model and SW groups, limb grip strength was increased, sarcomeres were basically normal, the myonuclear number and CSA were both greater, and the Pax7+ and MyoD+ cell numbers were both increased, significantly, in the CM group. Conclusion: Sijunzi decoction might increase the myonuclear number by activating the MSCs to treat limb weakness in SQD.

Recent advances in tissue stem cells

Stem cells are undifferentiated cells capable of self-renewal and differentiation,giving rise to specialized functional cells.Stem cells are of pivotal importance for organ and tissue development,homeostasis,and injury and disease repair.Tissue-specific stem cells are a rare population residing in specific tissues and present powerful potential for regeneration when required.They are usually named based on the resident tissue,such as hematopoietic stem cells and germline stem cells.This review discusses the recent advances in stem cells of various tissues,including neural stem cells,muscle stem cells,liver progenitors,pancreatic islet stem/progenitor cells,intestinal stem cells,and prostate stem cells,and the future perspectives for tissue stem cell research.

Regulation of muscle stem cell fate

Skeletal muscle plays a critical role in human health.Muscle stem cells(MuSCs)serve as the major cell type contribut-ing to muscle regeneration by directly differentiating to mature muscle cells.MuSCs usually remain quiescent with occasionally self-renewal and are activated to enter cell cycle for proliferation followed by differentiation upon muscle injury or under pathological conditions.The quiescence maintenance,activation,proliferation,and differentiation of MuSCs are tightly regulated.The MuSC cell-intrinsic regulatory network and the microenvironments work coordi-nately to orchestrate the fate transition of MuSCs.The heterogeneity of MuSCs further complicates the regulation of MuSCs.This review briefly summarizes the current progress on the heterogeneity of MuSCs and the microenviron-ments,epigenetic,and transcription regulations of MuSCs.

Myogenesis controlled by a long non-coding RNA 1700113A16RIK and post-transcriptional regulation

Long non-coding(lnc)RNA plays important roles in many cellular processes.The function of the vast majority of lncRNAs remains unknown.Here we identified that lncRNA-1700113A16RIK existed in skeletal muscle stem cells(MuSCs)and was significantly elevated during MuSC differentiation.Knockdown of 1700113A16RIK inhibits the differentiation of muscle stem cells.In contrast,overexpression of 1700113A16RIK promotes the differentiation of muscle stem cells.Further study shows the muscle specific transcription factor Myogenin(MyoG)positively regulates the expression of 1700113A16RIK by binding to the promoter region of 1700113A16RIK.Mechanistically,1700113A16RIK may regulate the expression of myogenic genes by directly binding to 3’UTR of an important myogenic transcription factor MEF2D,which in turn promotes the translation of MEF2D.Taken together,our results defined 1700113A16RIK as a positive regulator of MuSC differentiation and elucidated a mechanism as to how 1700113A16RIK regulated MuSC differentiation.