Myoid cell density in the thymus is reduced during mdx dystrophy and after muscle crush

1999 ◽  
Vol 77 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Annyue Wong ◽  
Kerryn L Garrett ◽  
Judy E Anderson

Thymic myoid cells share structural and behavioural features with cells of the skeletal muscle lineage: they express regulatory genes and contractile proteins, and they can form myofibers in culture. Historically, those features suggested that myoid cells could be precursors for muscle repair in addition to the satellite cells in muscle that are typically designated as the only muscle precursors. Muscles of the mutant mdx dystrophic mouse strain have a large demand for precursors, which is greatest at a young age. In the present study, immunostaining for troponin T was used to localize myoid cells. We tested the hypothesis that the myoid cell population changes when there is a demand for muscle precursors and that these changes would be anticipated if myoid cells have a role as myogenic precursors or stem cells in muscle. Chronic demands for muscle precursors in mdx dystrophic mice were accompanied by lower myoid cell density in comparison with density in two normal strains (C57BL10/ScSn and Swiss Webster). Acute demand for precursors was accompanied by a sharp decline in thymic myoid cell density within 2 days after a crush injury to one tibialis anterior muscle in normal but not dystrophic animals. To standardize the developmental age of the thymus, density was determined in all animals at 28 days of age. Given the current interest in nonmuscle sources of myogenic stem cells, these data suggest that changes in the density of thymic myoid cells may accompany acute and chronic demands for muscle precursors. Further experiments are required to determine whether thymic myoid cells are participants in distant muscle cell proliferation, new fiber formation, or the establishment of new stem cells in regenerated muscle.Key words: thymus, myoid cells, troponin T, MyoD, tissue repair, myoblasts, mdx dystrophy.

Development ◽  
2020 ◽  
Vol 147 (19) ◽  
pp. dev185975
Author(s):  
Maud Wurmser ◽  
Nathalie Chaverot ◽  
Rouba Madani ◽  
Hiroshi Sakai ◽  
Elisa Negroni ◽  
...  

ABSTRACTPax7 expression marks stem cells in developing skeletal muscles and adult satellite cells during homeostasis and muscle regeneration. The genetic determinants that control the entrance into the myogenic program and the appearance of PAX7+ cells during embryogenesis are poorly understood. SIX homeoproteins are encoded by the sine oculis-related homeobox Six1-Six6 genes in vertebrates. Six1, Six2, Six4 and Six5 are expressed in the muscle lineage. Here, we tested the hypothesis that Six1 and Six4 could participate in the genesis of myogenic stem cells. We show that fewer PAX7+ cells occupy a satellite cell position between the myofiber and its associated basal lamina in Six1 and Six4 knockout mice (s1s4KO) at E18. However, PAX7+ cells are detected in remaining muscle masses present in the epaxial region of the double mutant embryos and are able to divide and contribute to muscle growth. To further characterize the properties of s1s4KO PAX7+ cells, we analyzed their transcriptome and tested their properties after transplantation in adult regenerating tibialis anterior muscle. Mutant stem cells contribute to hypotrophic myofibers that are not innervated but retain the ability to self-renew.


2021 ◽  
Vol 525 ◽  
pp. 111179
Author(s):  
Xingxing Zhao ◽  
Xin Wen ◽  
Minpeng Ji ◽  
Xiaoju Guan ◽  
Panpan Chen ◽  
...  

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Kwiecien ◽  
L Drabik ◽  
A Mazurek ◽  
M Sikorska ◽  
L Czyz ◽  
...  

Abstract Introduction CIRCULATE-Acute Myocardial Infarction is a double-blind controlled trial randomizing (RCT) in 105 consecutive patients with their first, large AMI (cMRI-LVEF ≤45% and/or cMRI-infarct size ≥10% of LV) with successful infarct-related artery (IRA) primary percutaneous coronary intervention (pPCI) to transcoronary administration of Wharton's Jelly Mesenchymal Stem Cells (WJMSCs) vs. placebo (2:1). The pilot study cohort (PSC) preceded the RCT. Aim To evaluate WJMSCs long-term safety, and evolution of left-ventricular (LV) function in CIRCULATE-AMI PSC. Material and methods 30 000 000 WJMSCs (50% labelled with 99mTc-exametazime) were administered via IRA in a ten-patient PCS (age 32–65 years, peak hs-Troponin T 17.3±9.1ng/mL and peak CK-MB 533±89U/L, cMRI-LVEF 40.3±2.7% and infarct size 20.1±2.8%) at ≈5–7 days after AMI using a cell delivery-dedicated, coronary-non-occlusive method. Other treatments were per guidelines. WJMSCs showed an unprecedented high myocardial uptake (30.2±5.3%; 95% CI 26.9–33.5%), corresponding to ≈9×10 000 000 cells retention in the infarct zone – in absence of epicardial flow or myocardial perfusion impairment (TIMI-3 in all; cTFC 45±8 vs. 44±9, p=0.51) or any hs-Troponin T elevation. Five-year follow up included cardiac Magnetic Resonance Imaging (cMRI) (at baseline, 1 year and 3 years) and detailed echocardiography (echo) at baseline, 1 year, 3 years and 5 years. Results By 5 years, one patient died from a new, non-index territory AMI. There were no other cardiovascular events and MACCE that might be related to WJMSCs transplantation. On echo (Fig), there was an increase in left ventricular ejection fraction (LVEF) between WJMSCs administration point and 1 year (37.7±2.9% vs. 48.3±2.5%, p=0.002) that was sustained at 3 years (47.2±2.6%, p=0.005 vs. baseline) and at 5 years: (44.7±3.2%, p=0.039 vs. baseline). LVEF reached a peak at 1 year after the AMI and WJMSCs transfer (Fig). cMRI data (obtained up to 3 years; 1 year 41.9±2.6% vs. 51.0±3.3%, p<0.01; 3 years 52.2±4.0%, p<0.01 vs. baseline) were consistent with the echo LVEF assessment. Conclusions 5-year follow up in CIRCULATE-AMI PSC indicates that WJMSC transcoronary application is safe and may be associated with an LVEF improvement. The magnitude of LV increase appears to peak at 1 year, suggesting a potential role for repeated WJMSCs administration(s). Currently running double-blind RCT will provide placebo-controlled insights into the WJMSCs effect(s) on changes in LV function, remodelling, scar reduction and clinical outcomes. Echo-LVEF evolution Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): STRATEGMED 265761 “CIRCULATE” National Centre for Research and Development/Poland/ZDS/00564 Jagiellonian University Medical College


Biologija ◽  
2010 ◽  
Vol 56 (1) ◽  
pp. 55-62 ◽  
Author(s):  
Laima Degutytė-Fomins ◽  
Rasa Žūkienė ◽  
Odeta Buzaitė ◽  
Paulius Dzikas ◽  
Zita Naučienė ◽  
...  

2015 ◽  
Vol 4 (15) ◽  
pp. 2306-2313 ◽  
Author(s):  
Loran D. Solorio ◽  
Lauren M. Phillips ◽  
Alexandra McMillan ◽  
Christina W. Cheng ◽  
Phuong N. Dang ◽  
...  

2019 ◽  
Vol 1 (1) ◽  
pp. 01-05
Author(s):  
Stalin Reddy Challa ◽  
Swathi Goli

Degenerative muscle diseases affect muscle tissue integrity and function. Human embryonic stem cells (hESC) are an attractive source of cells to use in regenerative therapies due to their unlimited capacity to divide and ability to specialize into a wide variety of cell types. A practical way to derive therapeutic myogenic stem cells from hESC is lacking. In this study, we demonstrate the development of two serum-free conditions to direct the differentiation of hESC towards a myogenic precursor state. Using TGFß and PI3Kinase inhibitors in combination with bFGF we showed that one week of differentiation is sufficient for hESC to specialize into PAX3+/PAX7+ myogenic precursor cells. These cells also possess the capacity to further differentiate in vitro into more specialized myogenic cells that express MYOD, Myogenin, Desmin and MYHC, and showed engraftment in vivo upon transplantation in immunodeficient mice. Ex vivo myomechanical studies of dystrophic mouse hindlimb muscle showed functional improvement one month post-transplantation. In summary, this study describes a promising system to derive engrafting muscle precursor cells solely using chemical substances in serum-free conditions and without genetic manipulation.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Mo Xing

With the continued development of sports in China, sports sometimes cause cartilage damage. The purpose of this research is to study the tissue engineering scaffold material for sports cartilage damage repair. In this study, mesenchymal rat bone marrow stem cells (to put it simply, stem cells are a type of cell with unlimited or immortal self-renewal capacity, capable of producing at least one type of highly differentiated progeny cells) were obtained by the total bone wash method. The cells were inoculated into the cell culture bottle. When the primary cultured cells proliferated to about 80% of the culture bottle area, the cells were digested with trypsin to open the cell link, then the medium containing 10% serum was added to terminate the cell digestion, and then the passage expansion was carried out according to the cell density. PLGA/NHA and PLGA were heated to 65°C under ultrasonic vibration until uniform PLGA/NHA and PLGA solutions were obtained. Then, the samples were added to the tube mold and then heated and cooled to obtain the composite porous scaffold of mesenchymal stem cells. 10 μl MSCs cell suspension was extracted with a microinjector, and the needle was injected from the inside of the scaffold, and the cell suspension was added outside the scaffold to ensure that there were composite cells inside and outside the scaffold. The subcutaneous tissue of the skin was cut along the medial side of the knee joint and the capsule of the switch segment was cut. The scaffold materials were filled into the osteochondral defect to observe the cartilage healing. The mechanical strength of 0.5% PLGA-MSCs composite porous scaffold was increased to 1.1 MPa, and the cell density was high. The repair of cartilage in rats was the best. The results showed that the porous scaffolds designed in this study have good compatibility and are beneficial to repair sports cartilage injury.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Shayne Boucher ◽  
Stacy Jones ◽  
David Kuninger ◽  
Mohan Vemuri

Objective: Current protocols for differentiating pluripotent stem cells (PSCs) have led to heterogeneous results, varying purity levels, and long lead times for generation of cardiomyocytes. We hypothesized that a simplified and rapid cardiomyocyte differentiation media system can be developed in a scalable workflow to enable generation of large numbers of consistent, spontaneously active cardiomyocytes that could be used in basic and translational research. Methods: High quality PSCs were maintained under xenofree, feeder-free culture conditions. At time of passaging, PSC were dissociated with 0.5 mM EDTA, seeded on 1:100 Geltrex © -coated surface as small clusters at ~0.5 to 1 x 10 5 /well of a 12-well plate and maintained for four days under serum-free condition. After reaching target confluence of ~60 to 80%, an induction media was added for two days followed by addition of a second induction media for two days. After the induction step, the media was replaced with maintenance media and re-fed every other day for up to five weeks. PSC-derived cardiomyocytes were analyzed by morphology, gene expression, flow cytometry, immunocytochemistry and multi-electrode array (MEA). Results: We observed individual beating cells by Day 7 and contracting syncytia by Day 10. An over 100 fold increase in cell number was noted from the time of plating to generation of contracting syncytia of cardiomyocytes. Quantitative flow cytometry detected populations of troponin T type 2 (TNNT2)-immunoreactive cells that reached as high as 96.6%. Number of TNNT2-positive cells dropped by 20% when induced at 90% versus 60% confluency. PCR studies confirmed expression of mesoderm (T, MIXL1, MESP1), cardiac mesoderm (ISL1, GATA4, MEF2C) and mature cardiomyocyte genes (NKX2.5, TNNT2, MYH6). Immunocytochemistry studies verified expression of cardiac markers NKX2.5,GATA4, MEF2C, TNNT2 and MYH6. Initial MEA studies corroborated the presence of electrically active cells. Conclusions: We conclude that a simplified complete differentiation media system could serve as a standardized culture system for generating large numbers of consistent, spontaneously active cardiomyocytes for basic and translational research studies.


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