Application of Bone Marrow–Derived Mesenchymal Stem Cells for Muscle Healing After Contusion Injury in Mice

Abstract

Background: Skeletal muscle injuries are very common in sports medicine. Conventional therapies have limited clinical efficacy. New treatment methods should be developed to allow athletes to return to play with better function. Purpose: To evaluate the in vitro differentiation potential of bone marrow–derived mesenchymal stem cells and the in vivo histologic and physiologic effects of mesenchymal stem cell therapy on muscle healing after contusion injury. Study Design: Controlled laboratory study. Methods: Bone marrow cells were flushed from both femurs of 5-week-old C57BL/6 mice to establish immortalized mesenchymal stem cell lines. A total of 36 mice aged 8 to 10 weeks were used to develop a muscle contusion model and were divided into 6 groups (6 mice/group) on the basis of the different dosages of IM2 cells to be injected (0, 1.25 × 105, and 2.5 × 105 cells with/without F-127 in 100 μL of phosphate-buffered saline). Histological analysis of muscle regeneration was performed, and the fast-twitch and tetanus strength of the muscle contractions was measured 28 days after muscle contusion injury, after injections of different doses of mesenchymal stem cells with or without the F-127 scaffold beginning 14 days after contusion injury. Results: The mesenchymal stem cell–treated muscles exhibited numerous regenerating myofibers. All the groups treated with mesenchymal stem cells (1.25 × 105 cells, 2.5 × 105 cells, 1.25 × 105 cells plus F-127, and 2.5 × 105 cells plus F-127) exhibited a significantly higher number of regenerating myofibers (mean ± SD: 111.6 ± 14.77, 133.4 ± 21.44, 221.89 ± 32.65, and 241.5 ± 25.95, respectively) as compared with the control group and the control with F-127 (69 ± 18.79 and 63.2 ± 18.98). The physiologic evaluation of fast-twitch and tetanus strength did not reveal differences between the age-matched uninjured group and the groups treated with various doses of mesenchymal stem cells 28 days after contusion. Significant differences were found between the control group and the groups treated with various doses of mesenchymal stem cells after muscle contusion. Conclusion: Mesenchymal stem cell therapy increased the number of regenerating myofibers and improved fast-twitch and tetanus muscle strength in a mouse model of muscle contusion. However, the rapid decay of transplanted mesenchymal stem cells suggests a paracrine effect of this action. Treatment with mesenchymal stem cells at various doses combined with the F-127 scaffold is a potential therapy for a muscle contusion. Clinical Relevance: Mesenchymal stem cell therapy has an effect on sports medicine because of its effects on myofiber regeneration and muscle strength after contusion injury.

We Need Robust Nomenclature for Orthobiologics: Response

“…We would like to thank the authors for their interest in our paper entitled “Application of Bone Marrow–Derived Mesenchymal Stem Cells for Muscle Healing After Contusion Injury in Mice.” 4 We agree with the conclusion in the “Letter to the Editor” that “Until robust nomenclature has been established, researchers, clinicians, and industry should all strive to describe biologic preparations in a manner that is accurate and transparent.” The study of stem cells before the clinical usage in orthopaedic surgery should be focused on the characterization of the appropriate tissue environment into which certain stem cells are transplanted, that is, clarification of the mechanism of stem cell therapy—paracrine effect, immunomodulation, or direct engraftment; identification of factors that stimulate release, recruitment, and activation of native stem cells; development of serum‐free media for stem cell cultures and expansion; and identification of novel genetic markers and subsets of stem cells that specialize in different tissue types. 11 We also need to improve our understanding of the basic cellular and molecular mechanisms involved in traumatic events or degeneration and the following healing procedures of orthopaedic soft tissues (meniscus, articular cartilage, tendon, ligament, and muscle).…”

“…Chen et al 2 used the bone mesenchymal stromal cells (BMSCs) from 16-week-old New Zealand White rabbits in hydrogel, with or without transforming growth factor β1 (TGF-β1), to see their effects on 1.5 mm–diameter cylindrical defects created in the inner two‐thirds of the anterior angle of the lateral meniscus of 30 mature New Zealand White rabbits. Chiu et al 4 used immortalized mesenchymal stem cells lines (IM2 cells) 10 suspended in Pluronic F-127 (poloxamer 407; Sigma) to see the in vivo histologic and physiologic effects of mesenchymal stem cell therapy on mice muscle healing after contusion injury.…”

We Need Robust Nomenclature for Orthobiologics: Letter to Editor

“…We read with great interest the recent publications by Chiu et al 7 and Chen et al 6 evaluating the regenerative potential of bone marrow–derived mesenchymal stem cells (BMMSCs) and bone mesenchymal stromal cells (BMSCs), respectively. The basic regenerative substrate in both studies is cells derived from bone marrow with the ability to differentiate into bone, fat, and cartilage.…”

Biocompatibility of Bone Marrow-Derived Mesenchymal Stem Cells in the Rat Inner Ear following Trans-Tympanic Administration

“…MSCs are a heterogeneous population of cells with the ability to differentiate into multilineage cell types [25][26][27] The ability to replace different tissue types coupled with their immunomodulatory properties have suggested the critical role that MSCs can play in tissue repair. One of the major mechanisms for tissue damage is oxidative stress [39].…”

“…Additionally, MSCs can be autologously harvested, which mitigates the issue of immunologic rejection by the host. Experimentally, MSCs have been used as a cell source to replenish damaged tissue since they are capable of differentiating into various tissue types in response to environmental cues, such as secreted and insoluble growth factors -tumor growth factor (TGF)-alpha, TGF-beta, fibroblast growth factor (FGF)-2, insulin-like growth factor (IGF)-1, vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) -and chemokines (interleukin (IL)-1, IL2, IL-12, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma) [25][26][27]. MSCs are also known to reverse apoptosis in other cell types, such as cardiac myoblasts, neurons, and lung fibroblasts [28][29][30].…”