scholarly journals Satellite Cells: Regenerative Mechanisms and Applicability in Muscular Dystrophy

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Gustavo Torres de Souza ◽  
Rafaella de Souza Salomão Zanette ◽  
Danielle Luciana Aurora Soares do Amaral ◽  
Francisco Carlos da Guia ◽  
Claudinéia Pereira Maranduba ◽  
...  

The satellite cells are long regarded as heterogeneous cell population, which is intimately linked to the processes of muscular recovery. The heterogeneous cell population may be classified by specific markers. In spite of the significant amount of variation amongst the satellite cell populations, it seems that their activity is tightly bound to the paired box 7 transcription factor expression, which is, therefore, used as a canonical marker for these cells. Muscular dystrophic diseases, such as Duchenne muscular dystrophy, elicit severe tissue injuries leading those patients to display a very specific pattern of muscular recovery abnormalities. There have been works on the application of precursors cells as a therapeutic alternative for Duchenne muscular dystrophy and initial attempts have proven the cells inefficient; however later endeavours have proposed solutions for the experiments improving significantly the results. The presence of a range of satellite cells populations indicates the existence of specific cells with enhanced capability of muscular recovery in afflicted muscles.

1965 ◽  
Vol 43 (6) ◽  
pp. 817-828 ◽  
Author(s):  
M. Maini Webber ◽  
H. F. Stich

A high incidence of mitotic irregularities was observed when X-irradiated livers were induced to regenerate after a partial hepatectomy. Mitotic irregularities resulted in the formation of a heterogeneous cell population. As regeneration proceeded, the liver was found to be composed of two different cell populations: (i) one consisting of polyploid and aneuploid cells and incapable of giving rise to many descendants, and (ii) another consisting of apparently normal cells and capable of extensive proliferation which resulted in the formation of cell colonies. The regeneration of liver is mainly attributed to the cell colonies. No tumors appeared in the liver. These results demonstrate that a heterogeneous cell population of a "precancerous lesion" does not necessarily lead to the formation of a neoplasm. A selection pressure can be considered as necessary to favor the multiplication of cells with abnormal chromosome complements over that of cells with normal complements, as is seen in the livers of rats fed a chemical carcinogen. However, in the case of X-irradiated livers, normal cells seem to be favored.


Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1119
Author(s):  
Aleksandra Klimczak ◽  
Agnieszka Zimna ◽  
Agnieszka Malcher ◽  
Urszula Kozlowska ◽  
Katarzyna Futoma ◽  
...  

Duchenne muscular dystrophy (DMD) is a genetic disorder associated with a progressive deficiency of dystrophin that leads to skeletal muscle degeneration. In this study, we tested the hypothesis that a co-transplantation of two stem/progenitor cell populations, namely bone marrow-derived mesenchymal stem cells (BM-MSCs) and skeletal muscle-derived stem/progenitor cells (SM-SPCs), directly into the dystrophic muscle can improve the skeletal muscle function of DMD patients. Three patients diagnosed with DMD, confirmed by the dystrophin gene mutation, were enrolled into a study approved by the local Bioethics Committee (no. 79/2015). Stem/progenitor cells collected from bone marrow and skeletal muscles of related healthy donors, based on HLA matched antigens, were expanded in a closed MC3 cell culture system. A simultaneous co-transplantation of BM-MSCs and SM-SPCs was performed directly into the biceps brachii (two patients) and gastrocnemius (one patient). During a six-month follow-up, the patients were examined with electromyography (EMG) and monitored for blood kinase creatine level. Muscle biopsies were examined with histology and assessed for dystrophin at the mRNA and protein level. A panel of 27 cytokines was analysed with multiplex ELISA. We did not observe any adverse effects after the intramuscular administration of cells. The efficacy of BM-MSC and SM-SPC application was confirmed through an EMG assessment by an increase in motor unit parameters, especially in terms of duration, amplitude range, area, and size index. The beneficial effect of cellular therapy was confirmed by a decrease in creatine kinase levels and a normalised profile of pro-inflammatory cytokines. BM-MSCs may support the pro-regenerative potential of SM-SPCs thanks to their trophic, paracrine, and immunomodulatory activity. Both applied cell populations may fuse with degenerating skeletal muscle fibres in situ, facilitating skeletal muscle recovery. However, further studies are required to optimise the dose and timing of stem/progenitor cell delivery.


2018 ◽  
Vol 29 (2) ◽  
pp. 128-148 ◽  
Author(s):  
Katarzyna Pietraszek-Gremplewicz ◽  
Magdalena Kozakowska ◽  
Iwona Bronisz-Budzynska ◽  
Maciej Ciesla ◽  
Olga Mucha ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hidetoshi Sugihara ◽  
Naomi Teramoto ◽  
Katsuyuki Nakamura ◽  
Takanori Shiga ◽  
Taku Shirakawa ◽  
...  

Abstract Duchenne muscular dystrophy (DMD) is a progressive disease characterised by chronic muscle degeneration and inflammation. Our previously established DMD model rats (DMD rats) have a more severe disease phenotype than the broadly used mouse model. We aimed to investigate the role of senescence in DMD using DMD rats and patients. Senescence was induced in satellite cells and mesenchymal progenitor cells, owing to the increased expression of CDKN2A, p16- and p19-encoding gene. Genetic ablation of p16 in DMD rats dramatically restored body weight and muscle strength. Histological analysis showed a reduction of fibrotic and adipose tissues invading skeletal muscle, with increased muscle regeneration. Senolytic drug ABT263 prevented loss of body weight and muscle strength, and increased muscle regeneration in rats even at 8 months—the late stage of DMD. Moreover, senescence markers were highly expressed in the skeletal muscle of DMD patients. In situ hybridization of CDKN2A confirmed the expression of it in satellite cells and mesenchymal progenitor cells in patients with DMD. Collectively, these data provide new insights into the integral role of senescence in DMD progression.


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