ABSTRACT
Skeletal muscle injury is the most common problem in orthopedic and sports medicine, and severe injury leads to fibrosis and muscle dysfunction. Conventional treatment for successive muscle injury is currently controversial, although new therapies, like cell therapy, seem to be promise. We developed a model of successive injuries in rat to evaluate the therapeutic potential of bone marrow mesenchymal cells (BMMC) injected directly into the injured muscle. Functional and histological assays were performed 14 and 28 days after the injury protocol by isometric tension recording and picrosirius/Hematoxilin & Eosin staining, respectively. We also evaluated the presence and the fate of BMMC on treated muscles; and muscle fiber regeneration. BMMC treatment increased maximal skeletal muscle contraction 14 and 28 days after muscle injury compared to non-treated group (4.5 ± 1.7 vs 2.5 ± 0.98 N/cm2, p<0.05 and 8.4 ± 2.3 vs. 5.7 ± 1.3 N/cm2, p<0.05 respectively). Furthermore, BMMC treatment increased muscle fiber cross-sectional area and the presence of mature muscle fiber 28 days after muscle injury. However, there was no difference in collagen deposition between groups. Immunoassays for cytoskeleton markers of skeletal and smooth muscle cells revealed an apparent integration of the BMMC within the muscle. These data suggest that BMMC transplantation accelerates and improves muscle function recovery in our extensive muscle re-injury model.
Subject(s)
Bone Marrow Cells/metabolism , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/metabolism , Muscle Contraction , Muscle, Skeletal , Recovery of Function , Animals , Male , Muscle, Skeletal/injuries , Muscle, Skeletal/metabolism , Muscle, Skeletal/physiopathology , Rats , Rats, WistarABSTRACT
BACKGROUND: Cellular cardiomyoplasty with bone marrow derived stromal (MSC) and mononuclear (BMNC) cells has been shown to improve performance of infarcted hearts. We performed a comparative study with MSC and BMNC and tested the hypothesis that captopril treatment could enhance the beneficial effect of cell therapy in large myocardial infarctions. METHODS: Male syngeneic Wistar rats underwent experimental infarction and were randomized to receive 1-3 x 10(6) MSC, 10(8) BMNC or vehicle (BSS group). Two additional groups were treated with captopril and received 1-3 x 10(6) MSC (Cap.MSC) or vehicle (Cap). RESULTS: The ejection fraction (EF%) of MSC and BMNC-treated rats was higher than in the BSS rats, eight weeks after transplantation (33.0+/-4.0, 34.0+/-2.0 and 20.0+/-2.0% respectively, P<0.01). Both captopril-treated groups improved EF% similarly. But only captopril plus MSC treatment almost restored cardiac function to control levels, 8 weeks after injection (60.50+/-5.40% vs. 41.00+/-4.50% in Cap.MSC and Cap respectively, P<0.05). Many DAPI-labelled cells were found in the scar tissue of the left ventricle only in the Cap.MSC group. CONCLUSIONS: Cell transplantation with both MSC and BMNC produced a similar stabilisation of heart function, but the success of the cell engraftment and the recovery of cardiac performance were dependent on concomitant treatment with captopril.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/pharmacology , Bone Marrow Transplantation/methods , Captopril/pharmacology , Cardiomyoplasty/methods , Heart Failure/pathology , Leukocytes, Mononuclear/transplantation , Myocardial Infarction/pathology , Stromal Cells/transplantation , Animals , Cardiac Output/physiology , Echocardiography, Doppler, Color , Electrocardiography , Heart Failure/physiopathology , Male , Microscopy, Fluorescence , Myocardial Contraction/physiology , Myocardial Infarction/physiopathology , Rats , Rats, Wistar , Transplantation, IsogeneicABSTRACT
Postinfarct congestive heart failure is one of the leading causes of morbidity and mortality in developed and developing countries. The main purpose of this study was to investigate whether transplantation of bone marrow stromal cells (BMSC) directly into the myocardium could improve the performance of healed infarcted rat hearts. Cell culture medium with or without BMSC was injected into borders of cardiac scar tissue 4 wk after experimental infarction. Cardiac performance was evaluated 2 wk after cellular (n = 10) or medium (n = 10) injection by electro- and echocardiography. Histological study was performed 3 wk after treatment. Electrocardiography of BMSC-treated infarcted rats showed electrical and mechanical parameters more similar to those in control than in medium-treated animals: a normal frontal QRS axis in 6 of 10 BMSC-treated and all control rats and a rightward deviation of the QRS axis in all 10 medium-treated animals. BMSC treatment, assessed by echocardiography, improved fractional shortening (39.00 +/- 4.03%) compared with medium-treated hearts (18.20 +/- 0.74%) and prevented additional changes in cardiac geometry. Immunofluorescence microscopy revealed colocalization of 4',6-diamidino-2-phenylindole-labeled nuclei of transplanted cells with cytoskeletal markers for cardiomyocytes and smooth muscle cells, indicating regeneration of damaged myocardium and angiogenesis. These data provide strong evidence that BMSC implantation can improve cardiac performance in healed infarctions and open new promising therapeutic opportunities for patients with postinfarction heart failure.
