Adipose-Derived Stem-Cell Treatment of Skeletal Muscle Injury

Abstract

Background: The aim of the present study was to investigate whether adipose-derived stem cells could contribute to skeletal muscle-healing. Methods: Adipose-derived stem cells of male rats were cultured and injected into the soleus muscles of female rats. Two and four weeks after injections, muscles were tested fortetanic force (50 Hz). Histological analysis was performed to evaluate muscle collagen deposition and the number of centronucleated muscle fibers. In orderto track donor cells, chimerism was detected with use of real-time polymerase chain reaction targeting the male sex-determining region Y (SRY) gene. Results: Two weeks after cell injection, tetanus strength and the number of centronucleated regenerating myofibers, as well as the number of centronucleated regenerating myofibers, were higher in the treated group than they were in the control group (mean and standard error of the mean, 79.2 ± 5.0% versus 58.3 ± 8.1%, respectively [p < 0.05]; and 145 ± 36 versus 273 ± 18 per 103 myofibers, respectively [p < 0.05]). However, there were no significant differences at four weeks. Treatment did not decrease collagen deposition. Male gene was not detected in female host tissue at two and four weeks after engraftment by polymerase chain reaction analysis. Conclusions: Adipose-derived stem-cell therapy increased muscle repair and force at two weeks, but not four weeks, after injection, suggesting that adipose-derived stem-cell administration may accelerate muscle repair; however, the rapid disappearance of injected cells suggests a paracrine mechanism of action. Disclosure: One or more of the authors received payments or services, either directly or indirectly (i.e., via his or her institution), from a third party in support of an aspect of this work. None of the authors, or their institution(s), have had any financial relationship, in the thirty-six months prior to submission of this work, with any entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. Also, no author has had any other relationships, or has engaged in any other activities, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.

Trends in Mesenchymal Stem Cells' Applications for Skeletal Muscle Repair and Regeneration

“…When associated to Matrigel TM , early improvements were observed. However, such differences were no longer evident in a 4-week time point [87].…”

“…It is set that the engraftment potential of MSCs into a damaged tissue is not absolute. The numbers or percent of cells identified at different time points following injection invariably decreases [76,85,87,88], down to nearly as little as 10% of the initially delivered numbers in a couple of months [88].…”

“…Cells closer to undifferentiated state seem to elicit boosted initial responses, accelerating the onset of the process [87,97]. By contrast, specialized cells tend to provide a more gradual but sustained response.…”

“…However, others report that the delivery of MSCs 1 week after injury (in attempt to escape initial inflammatory reaction) seems to impair their engraftment since no trace was detected after only 2 weeks. Most surprisingly, the cells were delivered on a hydrogel vehicle [87] what had been described to positively influence the permanency of delivered cells at the lesion site [83]. It might suggest that the early inflammatory microenvironment modulates MSCs function and maintenance on site or that their modulatory effects on the inflammatory milieu affect their engraftment.…”

“…Lesion Model Delivery Mode/ Vehicle Reference hBM-MSCs CTX TA mice local injection [88,74,79,61] rBM-MSCs VML GTN rat ECM [98] rBM-MSCs CR SL rat local injection [103,90,91,84,85] rBM-MSCs CR SL rat systemic delivery [86] hUC-MSCs VML TA rat thrombin-based matrix [51,52,54] hUC-MSCs VML TA rat fibrin-based matrix [54] hUC-MSCs VML TA rat hyaluronan/ alginate-based hydrogel [54] hUC-MSCs (enriched) BVC TA rat local injection [67] hUC-MSCs CTX GTN mice local injection [76] hAT-MSCs (+ bFGF) LAC GTN mice hyaluronic acid-based hydrogel [83] rAT-MSCs LAC SL rat Matrigel TM [87] hAT-MSCs CTX TA mice local injection [74] hUCB-MSCs CTX GTN mice local injection [77] hSM-MSCs CTX TA mice local injection [2] systemic delivery hSM-MSCs CTX TA mice local injection [74] hDPSCs CTX TA mice local injection [75] Since the core topic of this section is in vivo skeletal regeneration of acquired lesions models, an important remark must be made. Although the general intrinsic regenerative response of the skeletal muscle tissue to an injury event (approached in detail earlier in this chapter) follows a mostly constant sequence of events, the source and the magnitude of the induced injury lead to distinct native healing efficiencies and consequently distinct responses to implemented therapies [27,104].…”