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Y chromosome-positive nuclei in endothelial cell. Immunofluorescent staining visualized by fluorescent microscopy shows XY-FISH combined with staining for the endothelial marker CD31 (green). The section was examined with a 100× objective. (A) Y chromosome (bright green, arrow), together with X chromosome (red, arrowhead) inside endothelial cell stained for CD31 (green). Nuclear DNA was counterstained by DAPI. Size bar = 10 μm. (B) Same image without CD31-staining for better visualization of chromosome staining.
Source publication
Background
During the past decade, several animal studies have demonstrated that in addition to local cells, cells from the bone marrow (BM) possess the ability to contribute to regeneration of injured skeletal muscle tissue. In addition, in mice, regular physical activity has been displayed to be a sufficient stimulus for BM-derived cell contribut...
Citations
... Satellite cells are widely accepted as the primary donors of myonuclei, but various lines of evidence suggest that alternative cell populations may contribute nuclei directly to muscle fibers. [212][213][214][215][216][217] Collectively, the amount and source of myonuclear turnover in adult skeletal muscle, and whether this is affected by exercise, are open questions that deserve further exploration. While muscle can adapt to an extent without satellite cells, it is currently unclear whether having augmented satellite cell number or function could enhance exercise adaptation through development and/ or in adulthood; human resistance training studies point to this possibility in some instances, 35,182,[218][219][220][221] but correlation does not mean causation. ...
Satellite cells support adult skeletal muscle fiber adaptations to loading in numerous ways. The fusion of satellite cells, driven by cell‐autonomous and/or extrinsic factors, contributes new myonuclei to muscle fibers, associates with load‐induced hypertrophy, and may support focal membrane damage repair and long‐term myonuclear transcriptional output. Recent studies have also revealed that satellite cells communicate within their niche to mediate muscle remodeling in response to resistance exercise, regulating the activity of numerous cell types through various mechanisms such as secretory signaling and cell–cell contact. Muscular adaptation to resistance and endurance activity can be initiated and sustained for a period of time in the absence of satellite cells, but satellite cell participation is ultimately required to achieve full adaptive potential, be it growth, function, or proprioceptive coordination. While significant progress has been made in understanding the roles of satellite cells in adult muscle over the last few decades, many conclusions have been extrapolated from regeneration studies. This review highlights our current understanding of satellite cell behavior and contributions to adaptation outside of regeneration in adult muscle, as well as the roles of satellite cells beyond fusion and myonuclear accretion, which are gaining broader recognition.
... Female patients that had received a bone marrow transplant from male donors 6-12 years previously, had rare skeletal muscle fibers (0.6%) with a nucleus that contained a Y chromosome. Although no Y chromosomes were present in the satellite cell niche on sections or in desmin-expressing myoblast cultures grown from isolated satellite cells, a rare Y chromosome-containing centrally located nucleus was detected, indicating that BMDCs had continued to add myonuclei to muscle (Strömberg et al. 2013). Thus, while BMDCs can contribute to muscle, it is extremely inefficient when the satellite cell pool is intact. ...
... In healthy subjects, homeostasis and repair of skeletal muscle rely on muscle-resident and circulating stem and progenitor cells, i.e., satellite cells and bone marrowderived hematopoietic and endothelial (CPCs) or mesenchymal stem and progenitor cells (MPCs). Mature endothelial cells (ECs) support myogenesis by growth factor secretion [1]. Myotonic dystrophy type 1 (MD1) is a multisystem disorder of genetic origin that causes muscle wasting and impaired muscle regeneration. ...
... It could also be a hint for disease-related degenerative effects such as increased cell apoptosis [13] possibly mediated by vitamin B12 reduction over time [14], since-among others-vitamin B12 is very important for normal hematopoiesis in bone marrow [15]. A constant withdrawal of CPCs to sites of muscle regeneration could also be a possibility [1]. ...
... Клетки костного мозга, как известно, участвуют в физиологической и посттравматической регенерации мышц, обеспечивают кроветворение [19][20][21]. В связи с этим, исследование функционального состояния костного мозга в условиях лазеротерапии скелетных мышц приобретает актуальное значение. ...
CYTOGENETIC DISTURBANCES IN THE CELLS OF THE BONE MARROW
AS A POSSIBLE SIDE EFFECT OF LASER THERAPY
(experimental study).
N.V.Bulyakova*, V.S.Azarova
A.N. Severtsov Institute of Problems of Ecology and Evolution, Russian Academy of Sciences, Moscow, Russia
Abstract
At present, in practical medicine, the combined effect of pulsed infrared and red lasers are often used. In this paper, we investigated the abnormalities in the chromosomal apparatus of bone marrow cells as a possible side effect of laser therapy under conditions of intense laser exposure. In adult mongrel rats, an ana-telophase method was used to perform a cytogenetic analysis of bone marrow cells after alternating combined action on each animal's shin with two types of lasers with different intensities and depth of penetration into biological tissues. Pulsed infrared laser, 890 nm, 1500 Hz, 5 sessions in contact labile mode, and emitting continuously red laser, 632.8 nm, 5 sessions in stable remote mode. In experiment-1, the duration of the procedures was 1 min. Each rat tibia was irradiated with a total dose of 1.65 - 1.80 J / cm2. In experiment-2, the duration of the procedures was 3 min. Each rat tibia was irradiated with a total dose of 4.95 - 5.40 J / cm2. After completion of laser exposure, the frequency of occurrence of cells with chromosomal abnormalities in irradiated bone marrow increased. The cytogenetic effect depended on the dose of laser irradiation. In experiment-1, there was a tendency for an increase in chromosomal aberrations in comparison with the control. In the spectrum of pathologies, there was an increase in the number of mitoses with bridges and fragments, and a significant decrease in cells with more severe pathology (bridges and fragments in one cell) and other aberrations (lagging and stuck together chromosomes). The number of mitoses with the 1-st bridge significantly decreased. In experiment-2, a three-fold increase in the irradiation dose contributed to a significant increase in chromosomal aberrations. At the same time, changes in the spectrum of pathologies had the same tendency as in experiment-1, but they were less active. The number of mitoses with 3 bridges increased significantly. On the basis of the results obtained, we come to the conclusion that under these laser exposure conditions there was an excess of physiological norm for the organism as a whole, which could cause disturbances in the chromosomal apparatus of bone marrow cells.
Key words: infrared laser (890 nm, 1500 Hz), red laser (632.8 nm), combined effect of lasers in vivo, rat bone marrow, cytogenetic effect, ana-telophase method.
... При сравнительно высоких дозах лазерного облучения (ЛО) некоторые исследователи наблюдали гибель клеток костного мозга, подавление колониеобразующей способности и пролиферативной активности мезенхимных стволовых клеток, а также увеличение ретикулоцитов с микроядрами, появление полиплоидных клеток и аберраций хроматидного типа уже после 3-5 сеансов ЛО бедренной косточки красным или инфракрасным лазерами [7][8][9][10][11]. Клетки костного мозга, как известно, участвуют в физиологической и посттравматической регенерации мышц, обеспечивают кроветворение [12][13][14]. В связи с этим исследование функционального состояния костного мозга в условиях лазеротерапии скелетных мышц становится актуальным. ...
The effect of combined alternating exposure to a laser emitting in the infrared and red wavelength ranges of the light spectrum on the bone marrow cells of the adult rats under conditions of both shin irradiation was investigated. The duration of the irradiation session was varied from 1 to 3 minutes. The ana-telophase method has demonstrated that the alternation of daily laser irradiation sessions of different intensity and depth of penetration into the biological tissues disturbed the division of bone marrow cells. This effect depended on the intensity of laser irradiation. Apparently, both the therapeutic corridor of laser therapy and the permissible energy irradiation were exceeded in the regime of laser therapy chosen for the present experiment, i.e. the combined alternation of exposure to pulsed infrared laser radiation (890 nm, 1500 Hz, contact labile mode) and continuous red laser radiation (632.8 nm in the remote steady mode) at a rate of 10 procedures per each animal’s hindlimb during two weeks.
... This may be due to several reasons, but it is tempting to speculate that the engrafted cells failed to reach full conversion to the satellite cell fate, as previously shown in other systems (Cossu, 2004;Lapidos et al., 2004). The relevance of circulating HSC fusion into heart and skeletal muscle are unclear, but the phenomenon keeps arising in the literature (Quijada and Sussman, 2015), and occurs also in human muscle (Stromberg et al., 2013). Based on these results we propose the PC as the most appropriate system to further understand the role of mobilized cells that engraft in skeletal muscle, a research area that has been neglected possibly because of the extreme rarity of the fusion events in the muscle groups that are most often analyzed. ...
... This may be due to several reasons, but it is tempting to speculate that the engrafted cells failed to reach full conversion to the satellite cell fate, as previously shown in other systems (Cossu, 2004;Lapidos et al., 2004). The relevance of circulating HSC fusion into heart and skeletal muscle are unclear, but the phenomenon keeps arising in the literature (Quijada and Sussman, 2015), and occurs also in human muscle (Stromberg et al., 2013). Based on these results we propose the PC as the most appropriate system to further understand the role of mobilized cells that engraft in skeletal muscle, a research area that has been neglected possibly because of the extreme rarity of the fusion events in the muscle groups that are most often analyzed. ...
The dermal Panniculus carnosus (PC) muscle is important for wound contraction in lower mammals and represents an interesting model of muscle regeneration due to its high cell turnover. The resident satellite cells (the bona fide muscle stem cells) remain poorly characterized. Here we analyzed PC satellite cells with regard to developmental origin and purported function. Lineage tracing shows that they originate in Myf5 + , Pax3/Pax7 + cell populations. Skin and muscle wounding increased PC myofiber turnover, with the satellite cell progeny being involved in muscle regeneration but with no detectable contribution to the wound-bed myofibroblasts. Since hemato-poietic stem cells fuse to PC myofibers in the absence of injury, we also studied the contribution of bone marrow-derived cells to the PC satellite cell compartment, demonstrating that cells of donor origin are capable of repopulating the PC muscle stem cell niche after irradiation and bone marrow transplantation but may not fully acquire the relevant myogenic commitment.
... Early reports suggesting that bone marrow-derived cells may regenerate damaged muscle after bone marrow trans-plantation 76,77 prompted investigators to explore myogenic precursor cell sources other than the satellite cell. [78][79][80] Although subsets of these cell types, such as mesenchymal stromal cells (MSCs), pericytes, and mesoangioblasts, reside in skeletal muscle and might present characteristics that make them suitable for regenerative purposes, 81-83 available data must be interpreted with caution. Physiologically unintended transdifferentiation of a small number of cells into nascent or immature skeletal myotubes, or even cell fusion events provoked by the surrounding myogenic niche environment, have been reported as true and meaningful in vivo muscular regeneration. ...
Urinary incontinence (UI) is the involuntary loss of urine and is a common condition in middle-aged and elderly women and men. Stress urinary incontinence (SUI) is caused by leakage of urine when coughing, sneezing, laughing, lifting, exercise or even standing leads to increased intraabdominal pressure. Other types of UI also exist such as urge incontinence (also called overactive bladder), which is a strong and unexpected sudden urge to urinate, mixed forms of UI that result in symptoms of both urge and stress incontinence and functional incontinence caused by reduced mobility, cognitive impairment or neuromuscular limitations that impair mobility or dexterity. However for many SUI patients there is significant loss of urethral sphincter muscle due to degeneration of tissue, the strain and trauma of pregnancy and childbirth or injury acquired during surgery. Hence, for individuals with SUI a cell-based therapeutic approach to regenerate the sphincter muscle offers the advantage of treating the cause rather than the symptoms. We discuss current clinically relevant cell therapy approaches for regeneration of the external urethral sphincter (striated muscle), internal urethral sphincter (smooth muscle), the neuromuscular synapse and blood supply. The use of mesenchymal stromal/stem cells (MSC) are a major step in the right direction, but they may not be enough for regeneration of all components of the urethral sphincter. Inclusion of other cell types or biomaterials may also be necessary to enhance integration and survival of the transplanted cells.
... This may be due to several reasons, but it is tempting to speculate that the engrafted cells failed to reach full conversion to the satellite cell fate, as previously shown in other systems (Cossu, 2004;Lapidos et al., 2004). The relevance of circulating HSC fusion into heart and skeletal muscle are unclear, but the phenomenon keeps arising in the literature (Quijada and Sussman, 2015), and occurs also in human muscle (Stromberg et al., 2013). Based on these results we propose the PC as the most appropriate system to further understand the role of mobilized cells that engraft in skeletal muscle, a research area that has been neglected possibly because of the extreme rarity of the fusion events in the muscle groups that are most often analyzed. ...
Our group has recently derived skeletal muscle from dermis-derived cells, by using an extracellular matrix that recreates the myogenic niche. After one week of differentiation, we observed isolated, twitching myotubes followed by spontaneous contractions of the entire tissue-engineered muscle construct. In vitro engineered myofibers expressed canonical markers, ultrastructure and electrophysiological characteristics of skeletal muscle. Interestingly, after one-month engineered muscle constructs showed progressive degradation of the myofibers concomitant with fatty infiltration, paralleling the natural course of muscular degeneration. However, we do not yet know how dermis-resident precursors are related with our isolated-myogenic precursors, a critical point for extrapolating our results to the human system. Knowing that dermal cells and muscle cells share a common embryonic origin from somite-derived dermomyotome and taking into account that there are different types of cells within the skin that have myogenic potential, our main objective is to identify and characterize the origin of murine dermal subpopulation with a myogenic potential, hypothesizing that may be (i) satellite cells from the Panniculus carnosus, (ii) dermomyotome-derived adult stem cells, (iii) perivascular cells and/or (iv) neural crest-derived precursor cells. For this end, lineage tracing experiments [(i) Pax3-GFP, (ii) Pax7CE, (iii) Myf5-Cre, (iv) CSPG4-Cre, and (v) Sox10-Cre] combined with FACS strategies and cellular differentiation assays have been developed. Our results show a high contribution of Myf5+ cells, a low contribution of Cspg4+ cells, and no contribution of Sox10+ cells to dermis-derived myogenic precursor cell subset. In principle, that means that dermomyotome-derived but not neural crest-derived cells are involved in subsequent engineered muscle differentiation.
In mammals, post-injury repair and regenerative events rely predominantly on stem cell function. Stem cell transplantation has achieved considerable success in animals but remains unfavorable for humans because of the unavoidable drawbacks. Nevertheless, substantial evidence suggests the regenerative potential of endogenous stem cells can be improved for functional and structural recovery of tissue damage or in diseases conditions. Endogenous stem cells are mostly quiescent under steady-state conditions and reside in their niche. Once faced with tissue injury, physiological and molecular changes within the niche or from distant tissues activate the migration, proliferation and differentiation of stem cells, contributing to tissue repair. Tissue regeneration is augmented by artificially amplifying the factors that promote stem cell mobilization or enhance the homing of endogenous stem cells. This cell-free strategy, known as "in situ tissue regeneration", represents a safer and more efficient means to conduct tissue regeneration. Bone marrow (BM) is considered the central niche and main reservoir of many types of stem cells. These stem cells hold great therapeutic potential for the regeneration of multiple injured tissues. Herein, we review recent strategies for promoting in situ tissue regeneration through BM-derived stem cell mobilization or homing in animal models as well as in human trials. With the advancement in biomaterial engineering, chemoattractant signals combined with functionalized bioscaffolds have accomplished sustained activation of endogenous BM-derived stem cells that can be used as an attractive strategy for efficient in situ tissue regeneration.
