scholarly journals Skeletal muscle repair by adult human mesenchymal stem cells from synovial membrane

2003 ◽  
Vol 160 (6) ◽  
pp. 909-918 ◽  
Author(s):  
Cosimo De Bari ◽  
Francesco Dell'Accio ◽  
Frank Vandenabeele ◽  
Joris R. Vermeesch ◽  
Jean-Marc Raymackers ◽  
...  

We have demonstrated previously that adult human synovial membrane-derived mesenchymal stem cells (hSM-MSCs) have myogenic potential in vitro (De Bari, C., F. Dell'Accio, P. Tylzanowski, and F.P. Luyten. 2001. Arthritis Rheum. 44:1928–1942). In the present study, we have characterized their myogenic differentiation in a nude mouse model of skeletal muscle regeneration and provide proof of principle of their potential use for muscle repair in the mdx mouse model of Duchenne muscular dystrophy. When implanted into regenerating nude mouse muscle, hSM-MSCs contributed to myofibers and to long term persisting functional satellite cells. No nuclear fusion hybrids were observed between donor human cells and host mouse muscle cells. Myogenic differentiation proceeded through a molecular cascade resembling embryonic muscle development. Differentiation was sensitive to environmental cues, since hSM-MSCs injected into the bloodstream engrafted in several tissues, but acquired the muscle phenotype only within skeletal muscle. When administered into dystrophic muscles of immunosuppressed mdx mice, hSM-MSCs restored sarcolemmal expression of dystrophin, reduced central nucleation, and rescued the expression of mouse mechano growth factor.

Author(s):  
A.R. Caseiro ◽  
T. Pereira ◽  
P.J. Bártolo ◽  
J.D. Santos ◽  
A.L. Luís ◽  
...  

2001 ◽  
Vol 44 (8) ◽  
pp. 1928-1942 ◽  
Author(s):  
Cosimo De Bari ◽  
Francesco Dell'Accio ◽  
Przemyslaw Tylzanowski ◽  
Frank P. Luyten

Nanoscale ◽  
2015 ◽  
Vol 7 (43) ◽  
pp. 18239-18249 ◽  
Author(s):  
Chunyan Zhao ◽  
Henrik Andersen ◽  
Barbaros Ozyilmaz ◽  
Sundara Ramaprabhu ◽  
Giorgia Pastorin ◽  
...  

PEG-CNT films spontaneously direct the skeletal myogenic differentiation of hMSCs in the absence of myogenic induction factors.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shiguo Yuan ◽  
Sheng Zheng ◽  
Kai Zheng ◽  
Yanping Gao ◽  
Meixiong Chen ◽  
...  

Abstract Background and objective Sympathetic activity plays an important role in the proliferation and differentiation of stem cells, and it changes over time, thereby exerting differential effects on various stem cell types. Aging causes sympathetic hyperactivity in aged tissues and blunts sympathetic nerves regulation, and sympathetic abnormalities play a role in aging-related diseases. Currently, the effect of sympathetic activity on skeletal muscle stem cells, namely satellite cells (SCs), is unclear. This study aimed to investigate the effects of skeletal muscle sympathetic activity on SC aging and skeletal muscle repair. Materials and methods To evaluate skeletal muscle and fibrotic areas, numbers of SCs and myonuclei per muscle fiber, β2-adrenoceptor (β2-ADR) expression, muscle repair, and sympathetic innervation in skeletal muscle, aged mice, young mice that underwent chemical sympathectomy (CS) were utilized. Mice with a tibialis anterior muscle injury were treated by barium chloride (BaCl2) and clenbuterol (CLB) in vivo. SCs or C2C12 cells were differentiated into myotubes and treated with or without CLB. Immunofluorescence, western blot, sirius red, and hematoxylin–eosin were used to evaluate SCs, myogenic repair and differentiation. Results The number of SCs, sympathetic activity, and reparability of muscle injury in aged mice were significantly decreased, compared with those in young mice. The above characteristics of young mice that underwent CS were similar to those of aged mice. While CLB promoted the repair of muscle injury in aged and CS mice and ameliorated the reduction in the SC number and sympathetic activity, the effects of CLB on the SCs and sympathetic nerves in young mice were not significant. CLB inhibited the myogenic differentiation of C2C12 cells in vitro. We further found that NF-κB and ERK1/2 signaling pathways were activated during myogenic differentiation, and this process could be inhibited by CLB. Conclusion Normal sympathetic activity promoted the stemness of SCs to thereby maintain a steady state. It also could maintain total and self-renewing number of SCs and maintain a quiescent state, which was correlated with skeletal SCs via β2-ADR. Normal sympathetic activity was also beneficial for the myogenic repair of injured skeletal muscle.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Emilie Barruet ◽  
Steven Garcia ◽  
Stanley Tamaki ◽  
Blanca M Morales ◽  
Jake Wu ◽  
...  

Abstract Developing optimal strategies for skeletal muscle regeneration and repair requires a detailed understanding of how these processes are regulated. The number of primary human satellite cells that can be obtained is usually extremely low, and may be impaired in disease of impaired skeletal muscle repair. One such condition is fibrodysplasia ossificans progressiva (FOP), a progressive disease characterized by massive heterotopic ossification in skeletal muscles and aberrant skeletal muscle repair after injury. FOP patients have activating mutations in the Activin A Type I receptor (ACVR1), a bone morphogenetic protein (BMP) receptor. Our overall hypothesis is that activated ACVR1 signaling caused by the ACVR1 R206H mutation incites inappropriate activation of human muscle stem cells (satellite cells, PAX7 expressing cells), causing loss of muscle cell fate and aberrant muscle repair. Since human satellite cells are difficult to obtain from live tissue donors, and injury can trigger heterotopic ossification, we created human induced pluripotent stem cell (iPSC)-derived muscle stem cells (iMuSCs) from FOP and control iPSC lines. We found that control and FOP iPSCs can differentiate into PAX7+ cells with high efficiency. Control and FOP iMuSCs can regenerate injured mouse muscle and form new human fibers, but both showed few PAX7 cells after transplant. Single cell RNA sequencing showed cell heterogeneity, and specific subsets of PAX7+ cells. FOP iMuSCs showed a chondrogenic/osteogenic signature (e.g COL1A1, DCN, OGN) with higher p38 pathway signaling activity. Skeletal muscle samples from autopsies of patients with FOP also showed increased expression of COL1A1. Additionally, we found that primary human FOP satellite cells can engraft and regenerate injured muscle, but with lower efficiency than control satellite cells. These studies used a novel iMuSC strategy to elucidate how increased ACVR1 activity affects human satellite cells function, and compare these iMuSCs to primary human satellite cells. These approaches will be useful to identify new therapeutic targets for conditions affecting skeletal muscle, and will improve our understanding of how muscle and bone interact in development and disease pathophysiology.


2020 ◽  
Author(s):  
Stefano Testa ◽  
Carles Sanchez Riera ◽  
Ersilia Fornetti ◽  
Federica Riccio ◽  
Claudia Fuoco ◽  
...  

AbstractSkeletal muscle tissue is characterized by restrained self-regenerative capabilities, being ineffective in relation to trauma extension both in time span (e.g. chronic diseases) and in size (e.g. large trauma). For these reasons, tissue engineering and/or cellular therapies represent a valuable solution in the cases where the physiological healing process failed. Satellite cells, the putative skeletal muscle stem cells, have been the first solution explored to remedy the insufficient self-regeneration capacity. Nevertheless, some limitation related to donor age, muscle condition, expansion hitch and myogenic potentiality maintenance have limited their use as therapeutic tool. To overcome this hindrance, different stem cells population with myogenic capabilities have been investigated to evaluate their real potentiality for therapeutic approaches, but, as of today, the perfect cell candidate has not been identified yet.In this work, we analyze the characteristics of skeletal muscle-derived human Mesenchymal Stem Cells (hMSCs), showing the maintenance/increment of myogenic activity upon differential culture conditions. In particular, we investigate the influence of a commercial enriched growth medium (Cyto-Grow), and of a medium enriched with either human-derived serum (H.S.) or Platelet-rich Plasma (PrP), in order to set up a culture protocol useful for employing this cell population in clinical therapeutic strategies. The presented results reveal the remarkable effects of H.S. in the enhancement of hMSC proliferation and myogenic differentiation.


2018 ◽  
Vol 315 (6) ◽  
pp. C885-C896 ◽  
Author(s):  
Jianming Guo ◽  
Haidi Hu ◽  
Jolanta Gorecka ◽  
Hualong Bai ◽  
Hao He ◽  
...  

We have previously shown that bone marrow-derived mesenchymal stem cells (BMSC) accelerate wound healing in a diabetic mouse model. In this study, we hypothesized that adipose tissue-derived stem cells (ADSC), cells of greater translational potential to human therapy, improve diabetic wound healing to a similar extent as BMSC. In vitro, the characterization and function of murine ADSC and BMSC as well as human diabetic and nondiabetic ADSC were evaluated by flow cytometry, cell viability, and VEGF expression. In vivo, biomimetic collagen scaffolds containing murine ADSC or BMSC were used to treat splinted full-thickness excisional back wounds on diabetic C57BL/6 mice, and human healthy and diabetic ADSC were used to treat back wounds on nude mice. Wound healing was evaluated by wound area, local VEGF-A expression, and count of CD31-positive cells. Delivery of murine ADSC or BMSC accelerated wound healing in diabetic mice to a similar extent, compared with acellular controls ( P < 0.0001). Histological analysis showed similarly increased cellular proliferation ( P < 0.0001), VEGF-A expression ( P = 0.0002), endothelial cell density ( P < 0.0001), numbers of macrophages ( P < 0.0001), and smooth muscle cells ( P < 0.0001) with ADSC and BMSC treatment, compared with controls. Cell survival and migration of ADSC and BMSC within the scaffolds were similar ( P = 0.781). Notch signaling was upregulated to a similar degree by both ADSC and BMSC. Diabetic and nondiabetic human ADSC expressed similar levels of VEGF-A ( P = 0.836) in vitro, as well as in scaffolds ( P = 1.000). Delivery of human diabetic and nondiabetic ADSC enhanced wound healing to a similar extent in a nude mouse wound model. Murine ADSC and BMSC delivered in a biomimetic-collagen scaffold are equivalent at enhancing diabetic wound healing. Human diabetic ADSC are not inferior to nondiabetic ADSC at accelerating wound healing in a nude mouse model. This data suggests that ADSC are a reasonable choice to evaluate for translational therapy in the treatment of human diabetic wounds.


Sign in / Sign up

Export Citation Format

Share Document