Transplantation Of Skeletal Muscle Research Articles

Algal-derived macromolecules and their composites: From synthetic biology to biomedical applications in bone and cardiovascular tissue engineering

Algae have shown numerous advantages as biofunctional and bioactive material sources. The development of biosynthetic or synthetic materials has enabled algal-derived macromolecules and their derivatives to be used in biomedical applications. This review examines and analyzes the most recent developments in the production of biomaterials from algal-derived macromolecules and their composites and their potential applications in bone and cardiovascular tissue engineering. Several macromolecules derived from algal polysaccharides, including sulfated polysaccharides, fucoidans, and fucans, have been developed for cartilage, intervertebral disc, bone, and skeletal muscle transplants because of their stable structures. Alginates, fucoidans, chitin, porphyrin, and other algal polysaccharide derivatives have been investigated for engineering blood vessels, heart valves, and even the liver. One advantage of algal-derived macromolecules and composites is their safe immunity properties. This review also highlights cutting-edge developments in applying algal-derived macromolecules with a broader biomedical scope to encourage in-depth research into their potential as biomaterial scaffolds in medical applications.

Study on the Effect of PDA-PLGA Scaffold Loaded With Islet Cells for Skeletal Muscle Transplantation in the Treatment of Diabetes.

At present, islet cells transplantation was limited by the way in which islet cells are implanted into the body, their ability to adapt to the microenvironment and the maintenance time for relieving diabetic symptoms. In order to solve this problem, we made PDA-PLGA scaffold loaded with islet cells and used it for skeletal muscle transplantation to investigate its therapeutic effect in the treatment of diabetes. The PLGA scaffold was prepared by the electrospinning method, and modified by polydopamine coating. A rat diabetic model was established to evaluate the efficacy of PDA-PLGA scaffold loaded with RINm5f islet cells through skeletal muscle transplantation. The results showed that the PDA-PLGA scaffold has good biosafety performance. At the same time, transplantation of the stent to the skeletal muscle site had little effect on the serum biochemical indicators of rats, which was conducive to angiogenesis. The PDA-PLGA scaffold had no effect on the secretory function of pancreatic islet cells. The PDA-PLGA scaffold carrying RINm5f cells was transplanted into the skeletal muscle of type I diabetic rats. 1 week after the transplantation of the PDA-PLGA cell scaffold complex, the blood glucose of the treatment group was significantly lower than that of the model group (p < 0.001) and lasted for approximately 3 weeks, which further indicated the skeletal muscle transplantation site was a new choice for islet cell transplantation in the future.

Engraftment of FACS Isolated Muscle Stem Cells into Injured Skeletal Muscle.

Skeletal muscle stem cell (MuSC) isolation and transplantation are invaluable tools to assess their capacity for self-renewal and tissue repair. Significant technical advances in recent years have led to the optimization of these approaches, improving our ability to assess MuSC regenerative potential. Here, we describe the procedures for Fluorescent Activated Cell Sorting (FACS)-based isolation of MuSC, their intramuscular transplantation, and analysis of their engraftment into host tissues.

Normal and Malignant Muscle Cell Transplantation into Immune Compromised Adult Zebrafish

Zebrafish have become a powerful tool for assessing development, regeneration, and cancer. More recently, allograft cell transplantation protocols have been developed that permit engraftment of normal and malignant cells into irradiated, syngeneic, and immune compromised adult zebrafish. These models when coupled with optimized cell transplantation protocols allow for the rapid assessment of stem cell function, regeneration following injury, and cancer. Here, we present a method for cell transplantation of zebrafish adult skeletal muscle and embryonal rhabdomyosarcoma (ERMS), a pediatric sarcoma that shares features with embryonic muscle, into immune compromised adult rag2E450fs homozygous mutant zebrafish. Importantly, these animals lack T cells and have reduced B cell function, facilitating engraftment of a wide range of tissues from unrelated donor animals. Our optimized protocols show that fluorescently labeled muscle cell preparations from α-actin-RFP transgenic zebrafish engraft robustly when implanted into the dorsal musculature of rag2 homozygous mutant fish. We also demonstrate engraftment of fluorescent-transgenic ERMS where fluorescence is confined to cells based on differentiation status. Specifically, ERMS were created in AB-strain myf5-GFP; mylpfa-mCherry double transgenic animals and tumors injected into the peritoneum of adult immune compromised fish. The utility of these protocols extends to engraftment of a wide range of normal and malignant donor cells that can be implanted into dorsal musculature or peritoneum of adult zebrafish.

Normal and malignant muscle cell transplantation into immune compromised adult zebrafish.

Zebrafish have become a powerful tool for assessing development, regeneration, and cancer. More recently, allograft cell transplantation protocols have been developed that permit engraftment of normal and malignant cells into irradiated, syngeneic, and immune compromised adult zebrafish. These models when coupled with optimized cell transplantation protocols allow for the rapid assessment of stem cell function, regeneration following injury, and cancer. Here, we present a method for cell transplantation of zebrafish adult skeletal muscle and embryonal rhabdomyosarcoma (ERMS), a pediatric sarcoma that shares features with embryonic muscle, into immune compromised adult rag2E450fs homozygous mutant zebrafish. Importantly, these animals lack T cells and have reduced B cell function, facilitating engraftment of a wide range of tissues from unrelated donor animals. Our optimized protocols show that fluorescently labeled muscle cell preparations from α-actin-RFP transgenic zebrafish engraft robustly when implanted into the dorsal musculature of rag2 homozygous mutant fish. We also demonstrate engraftment of fluorescent-transgenic ERMS where fluorescence is confined to cells based on differentiation status. Specifically, ERMS were created in AB-strain myf5-GFP; mylpfa-mCherry double transgenic animals and tumors injected into the peritoneum of adult immune compromised fish. The utility of these protocols extends to engraftment of a wide range of normal and malignant donor cells that can be implanted into dorsal musculature or peritoneum of adult zebrafish.

Combination of Hypoxic Preconditioning and Postconditioning Does Not Induce Additive Protection of Ex Vivo Human Skeletal Muscle From Hypoxia/Reoxygenation Injury

We previously demonstrated that hypoxic preconditioning (HPreC) or postconditioning (HPostC) protected ex vivo human skeletal muscle from hypoxia/reoxygenation injury. Here, we investigated if combined HPreC and HPostC could convey additive protection. Human rectus abdominis muscle strips were cultured in normoxic Krebs buffer for 5 hours (control) or in 3 hours hypoxic/2 hours normoxic buffer (treatment groups). HPreC and HPostC were induced by 1 cycle of 5 minutes hypoxia/5 minutes reoxygenation immediately before or after 3 hours hypoxia, respectively. Muscle injury, viability, and adenosine triphosphate (ATP) synthesis were assessed by measuring lactate dehydrogenase release, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide reduction, and ATP content, respectively. Hypoxia/reoxygenation caused lactate dehydrogenase to increase and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide reduction and ATP content to decrease (P < 0.05; n = 7). HPreC, HPostC, and combination of both were equally effective in protection of muscle from hypoxia/reoxygenation injury. Atractyloside (5 × 10 M), a mitochondrial permeability transition pore opener, abolished the protective effect of HPreC or HPostC. We conclude that HPreC and HPostC protect ex vivo human skeletal muscle against hypoxia/reoxygenation injury by closing the mitochondrial permeability transition pore. For that reason, they are equally effective and do not demonstrate an additive effect. Moreover, the potent effect of HPostC indicates ischemic postconditioning as an effective clinical intervention against reperfusion injury in autogenous skeletal muscle transplantation and replantation surgery.

Stem Cell Therapy for Stress Urinary Incontinence: A Critical Review

Stress urinary incontinence (SUI) is a prevailing health problem that severely impacts quality of life. Because SUI is mainly due to urethral sphincter deficiency, several preclinical and clinical trials have investigated whether transplantation of patient's own skeletal muscle-derived cells (SkMDCs) can restore the sphincter musculature. The specific cell type of SkMDCs has been described as myoblasts, satellite cells, muscle progenitor cells, or muscle-derived stem cells, and thus may vary from study to study. In more recent years, other stem cell (SC) types have also been tested, including those from the bone marrow, umbilical cord blood, and adipose tissue. These studies were mostly preclinical and utilized rat SUI models that were established predominantly by pudendal or sciatic nerve injury. Less frequently used animal models were sphincter injury and vaginal distension. While transurethral injection of SCs was employed almost exclusively in clinical trials, periurethral injection was used in all preclinical trials. Intravenous injection was also used in one preclinical study. Functional assessment of therapeutic efficacy in preclinical studies has relied almost exclusively on leak point pressure measurement. Histological assessment examined the sphincter muscle content, existence of transplanted SCs, and possible differentiation of these SCs. While all of these studies reported favorable functional and histological outcomes, there are questions about the validity of the animal model and claims of multilineage differentiation. In any event, SC transplantation appears to be a promising treatment for SUI.

Endoscopic injection of skeletal muscle–derived cells augments gut smooth muscle sphincter function: implications for a novel therapeutic approach

Sphincter function is a common problem in gastroenterology and leads to disorders such as GERD and fecal incontinence. We hypothesized that transplantation of skeletal muscle-derived cells (MDCs) into GI sphincters may improve their function, leading to a more physiological approach to treating these disorders. We performed experiments to test the potential of MDCs to survive and differentiate within the GI smooth muscle in order to gain further knowledge on the biology of skeletal muscle transplantation in GI smooth muscle sphincters as well as to test the safety and feasibility of endoscopic injection of MDCs in a large animal model. Animal laboratory. Adult male Sprague-Dawley rats and adult male beagle dogs were used. Rat-derived and dog-derived MDCs were prepared in vitro and labeled with DiI. DiI-labeled, rat-derived MDCs (200,000/4 muL phosphate buffered saline solution) were injected bilaterally in the pyloric wall of rats, and survival, differentiation, and in vitro contractility were assessed 1 month after transplantation. Dog-derived MDCs (4.0 x 10(6) cells) were also injected into the lower esophageal sphincter of 3 beagle dogs by using a standard variceal sclerotherapy needle after baseline esophageal manometry and pH monitoring. The dogs were treated with daily cyclosporine, and 2 weeks later esophageal manometry was repeated and the esophagus was examined histologically. Differentiation of grafted cells was assessed by immunofluorescence, using specific antibodies to markers of the smooth muscle phenotype (smooth muscle actin) and of the skeletal muscle phenotype (skeletal muscle myosin). In rats, grafted MDCs were visualized based on DiI fluorescence and were found to be localized within the muscle wall and in the muscularis mucosa. In vitro organ bath studies showed a significant increase in the contractile response of the pyloric sphincter to exogenous acetylcholine. In dogs, MDC injection resulted in a significant increase in baseline lower esophageal sphincter pressure. Further, in 1 dog with significant baseline acid reflux, MDC injection resulted in a reduction of acid reflux, with the fraction of time with pH <4 decreasing from 26.5% to 1.5%. Transplanted MDCs were seen adding bulk to the lower esophageal area and were well-integrated into the surrounding tissue. Immunofluorescence analysis revealed weak expression of skeletal muscle myosin in grafted MDCs and no expression of smooth muscle actin in either rats or dogs. Animal study. MDCs can survive and integrate into GI smooth muscle and augment their contractile response. Thus, they may have potential for the treatment of a variety of conditions.

Antioxidant Levels Represent a Major Determinant in the Regenerative Capacity of Muscle Stem Cells

Stem cells are classically defined by their multipotent, long-term proliferation, and self-renewal capabilities. Here, we show that increased antioxidant capacity represents an additional functional characteristic of muscle-derived stem cells (MDSCs). Seeking to understand the superior regenerative capacity of MDSCs compared with myoblasts in cardiac and skeletal muscle transplantation, our group hypothesized that survival of the oxidative and inflammatory stress inherent to transplantation may play an important role. Evidence of increased enzymatic and nonenzymatic antioxidant capacity of MDSCs were observed in terms of higher levels of superoxide dismutase and glutathione, which appears to confer a differentiation and survival advantage. Further when glutathione levels of the MDSCs are lowered to that of myoblasts, the transplantation advantage of MDSCs over myoblasts is lost when transplanted into both skeletal and cardiac muscles. These findings elucidate an important cause for the superior regenerative capacity of MDSCs, and provide functional evidence for the emerging role of antioxidant capacity as a critical property for MDSC survival post-transplantation.

Growth, differentiation, transplantation and survival of human skeletal myofibers on biodegradable scaffolds

Skeletal muscle transplantation strategies for muscle repair or gene therapy involve either the injection of proliferating myoblasts followed by fusion with host myofibers or implantation of ex vivo differentiated myofibers; however, both implant procedures are associated with significant cell loss. Biodegradable porous, gas-foamed poly-lactide-co-glycolide (PLG) scaffolds have desirable characteristics for cell transfer and were used to study attachment, growth, differentiation and survival of human myogenic cells. Primary human myoblasts suspended in clinical grade extracellular matrixes (ECMs) and adhered to PLG scaffolds differentiated in vitro into high-density tropomyosin positive myofibers. An immunodeficient non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mouse implant model was used to study the transfer and in vivo survival of differentiated human myofibers on these scaffolds. Scaffold rigidity allowed the myofibers to be maintained under tension in vitro and following subcutaneous transplantation in vivo. Following implantation, myofiber density on the PLG scaffolds decreased linearly by 78% over a 4-week period. ECM composed of either Tisseel fibrin or Zyderm collagen type I did not significantly affect in vivo cell viability over the 4-week period. Varying PLG scaffold microsphere content (10-100%) also had little effect on cell survival in vivo. In contrast, when the residual NK cell population in the immunodeficient NOD/SCID mouse model was depleted with anti-asialo GM1 (ASGM1) antiserum, in vivo cell survival significantly increased from 22% to 34% after 4 weeks. With further improvements in cell survival, PLG scaffolds may prove useful for the implantation of primary human myofibers in future clinical applications.

CNS innervation to the heart after skeletal muscle transplantation in the rat

The congestive heart failure is known as one of the most popular cause of human death. The purpose of this study were to identify the CNS pathway innervating heart after reconstruction using latissimus dorsi muscle by using the pseudorabies virus injection into the hippocampus after entorhinal cortex lesions.The pseudorabies virus labelled neurons were distributed at several different nuclei including paraventricular nucleus. No significant morphological changes were observed in the CNS heart innervation after reconstruction. These data suggested that the CNS innervation showed no morphological changes throughout the whole brain areas after heart reconstruction.

Adeno-associated virus-mediated vascular endothelial growth factor gene therapy in skeletal muscle before transplantation promotes revascularization of regenerating muscle.

Successful clinical transplantation of whole skeletal muscles can be limited by impaired muscle revascularization and regeneration. The aim of this study was to enhance the revascularization (and hence speed of regeneration) of transplanted whole muscles by transducing muscles with the vascular endothelial growth factor (VEGF) gene before transplantation, using a recombinant adeno-associated virus (rAAV). The rAAV encoding VEGF and green fluorescent protein (GFP) (rAAV.VEGF.GFP) was injected into the tibialis anterior muscles of adult BALB/c mice. One month after injection whole muscle autotransplantation was performed. Muscles were sampled 7 days after autografting. GFP expression was examined as an indicator of persistent transgene expression after grafting, and immunohistochemistry was used to identify VEGF, blood vessels, and newly formed myotubes. After grafting, GFP expression persisted only in a few surviving myofibers in the periphery of rAAV.VEGF.GFP-pretreated muscles, although abundant VEGF expression was seen in myogenic cells in all grafted muscles. Quantitative analysis demonstrated that, although only small numbers of rAAV.VEGF.GFP-transduced myofibers were present, whole muscle grafts preinjected with rAAV.VEGF.GFP were significantly more vascular than saline-injected and uninjected control muscle grafts. Furthermore, rAAV.VEGF.GFP-injected whole muscle transplants were further advanced in terms of regeneration (myotube formation) compared with the uninjected control muscle transplants. This study clearly shows that rAAV-mediated VEGF expression persists only in myofibers that survive the necrosis induced by muscle transplantation; however, this amount of VEGF results in significantly increased revascularization and regeneration of whole muscle transplants.

Myoblast transplantation for heart failure

Intramyocardial skeletal muscle transplantation has been shown experimentally to improve heart function after infarction. We report success with this procedure in a patient with severe ischaemic heart failure. We implanted autologous skeletal myoblasts into the postinfarction scar during coronary artery bypass grafting of remote myocardial areas. 5 months later, there was evidence of contraction and viability in the grafted scar on echocardiography and positron emission tomography. Although this result is encouraging, it requires validation by additional studies.

Blood borne macrophages are essential for the triggering of muscle regeneration following muscle transplant.

The transplantation of satellite cells may constitute a strategy for rebuilding muscle fibres in inherited myopathies. However, its development requires a great understanding of the role of environmental signals in the regenerative process. It is therefore essential to identify the key events triggering and controlling this process in vivo. We investigated whether macrophages play a key role in the course of the regenerative process using skeletal muscle transplants from transgenic pHuDes-nls-LacZ mice. Before grafting, transplants were conditioned with macrophage inflammatory protein 1-beta (MIP 1-beta; stimulating the macrophages infiltration or vascular endothelial growth factor (VEGF) stimulating angiogenesis). Treatment of transplants with MIP 1-beta and VEGF both accelerated and augmented monocyte-macrophage infiltration and satellite cell differentiation and/or proliferation, as compared to controls. In addition, VEGF treatment enhanced the number of newly formed myotubes. When a complete depletion of host monocyte-macrophages was experimentally induced, no regeneration occurred in transplants. Our data suggest that the presence of blood borne macrophages is required for triggering the earliest events of skeletal muscle regeneration. The understanding of macrophage behaviour after muscle injury should allow us to develop future strategies of satellite cell transplantation as a treatment for muscular dystrophies.

REJECTION PATTERN OF SIMULTANEOUSLY TRANSPLANTED CARDIAC AND SKELETAL MUSCLE IN A RAT MODEL.

408 Purpose: We sought to correlate cardiac and skeletal muscle allograft rejection in a heterotopic heart transplant rat model for the following purposes: 1) to quantitate the degree and severity of skeletal muscle rejection based on the grading system for cardiac muscle rejection, and 2) to assess the feasibility of use of biopsies from simultaneously transplanted skeletal muscle for surveillance of cardiac rejection.Methods: 34 Lewis (RT11) rats underwent simultaneous heterotopic cardiac and cutaneous maximus skeletal muscle transplants. Of those, 7 rats (Group I) received syngenic grafts from Lewis donors with no immunosuppression and served as control. The remaining 25 rats received allografts from Brown Norway (RT1n) donors in two groups: Group II(n=22) received no immunosuppression, and Group III (n=5) received one week of cyclosporine. Non-immunosuppressed rats (Groups I & II) were sacrificed at days 1 through 7 after the transplant whereas immunosuppressed rats (Group III) were sacrificed at 4 weeks. Tissue sections from the grafts were graded for cellular rejection based on the grading system of the Heart Rejection Study Group (International Society for Heart and Lung Transplantation, ISHLT).Results: All group I and III grafts were functional at 7 days post-transplant with no evidence of rejection. Of group II, 2 rats showed no signs of cardiac or skeletal muscle rejection when sacrificed on day 1. All the other rats (n=20) developed graft rejection within one week after the transplant. Cellular rejection correlated grade for grade in 17/20 (85%). Of the three rats that did not show grade to grade correlation, the cardiac biopsy was interpreted as Grade IA in one case when the skeletal muscle showed no rejection. In each of the other two cases, the heart showed focal solitary lymphocytic infiltrate with myocyte replacement (Grade II), and the muscle flap showed diffuse perivascular and interstitial lymphocytic infiltrates without myocyte necrosis (Grade IB). The severity of rejection correlated in 19/20 (95%) rats: mild rejection (Grades IA, IB, II): 9/10 rats (90%); moderate (IIIA, IIIB): 6/6 (100%) and severe (IV): 4/4 (100%).Conclusion: Skeletal muscle rejection may be quantitated using the ISHLT grading system for cardiac muscle rejection. Cardiac and skeletal muscle allografts had similar pattern and severity of rejection with little grade to grade variability. The clinical implications of this correlation for surveillance of cardiac rejection warrants further investigation.

Desmin-lacZ transgene expression and regeneration within skeletal muscle transplants.

The purpose of this study was to investigate the initiation and time course of the regeneration process in fragments of skeletal muscle transplants as a function of muscle tissue age at implantation. The appearance of desmin occurs at the very beginning of myogenesis. The transgenic desmin nls lacZ mice used in the study bear a transgene in which the 1 kb DNA 5' regulatory sequence of the desmin gene is linked to a reporter gene coding for Escherichia coli beta-galactosidase. The desmin lacZ transgene labels muscle cells in which the desmin synthesis programme has commenced. We implanted pectoralis muscle fragments from fetal transgenic embryos and mature and old transgenic mice into mature non-transgenic mice. Early events of myogenesis occurring during regeneration started sooner in transplants from 4-month-old (day 3 post-implantation) muscle than in those from 24-month-old (day 5-6 post-implantation) muscle, and they lasted longer in those from young (day 17 post-implantation) than in those from old (day 14 post-implantation) muscle fragments. In adult muscle, transgene activation proceeded from the periphery toward the centre of the transplant. In transplants from fetal 18-day-old pectoralis, myotubes with transgene activity were observed from day 1 to day 19. Desmin immunoreactivity, which appeared about one day after transgene activation, was followed by myosin expression. In adult transplants, the continuity of laminin labelling was disrupted around degenerative fibres, illustrating alteration of the extracellular matrix. Our data suggest that satellite cells from old muscle tissue have lower proliferative capacity and/or less access to trophic substances released by the host (damaged fibres, vascularization) than those from fetal or young adult muscle.

Quantitative analysis for histochemical grouping of muscle fibres after skeletal muscle transplantation by microneurovascular anastomoses: XM Gu, SH Chou, PL Lau, LK Yan, SM Suen, SK Wu, Chin J Stomatol 1994; 29(3): 131–133

Quantitative analysis for histochemical grouping of muscle fibres after skeletal muscle transplantation by microneurovascular anastomoses: XM Gu, SH Chou, PL Lau, LK Yan, SM Suen, SK Wu, Chin J Stomatol 1994; 29(3): 131–133

Regeneration pattern of cardiac and skeletal muscle after transplantation into a skeletal muscle bed in rats.

The ability of skeletal muscle to regenerate after injury is well established. In contrast, cardiac muscle is incapable of regeneration and recovery after injury. The aim of the present study was to evaluate and compare the regeneration pattern of cardiac and skeletal muscle after transplantation into a skeletal muscle bed in rats. The following group of transplants were performed at the site prepared by removing the host extensor digitorum longus (EDL) muscle. The first group consisted of cardiac muscle transplanted as one piece or after mincing into 1-mm pieces. The second group included cotransplants of cardiac and skeletal muscle minces that were intermixed. Entire EDL muscle or minced EDL muscle were also transplanted for comparison. Rats were sacrificed 3-30 days after transplantation for morphological analysis. The results demonstrated that skeletal muscle transplants underwent rapid regeneration, and by 30 days the entire muscle was filled with regenerated myofibers. In transplants of cardiac muscle significant inflammation, myocardial degeneration and necrosis were observed. In spite of the necrosis and fibrosis, the presence of a few regenerated myotubes in the outer region was observed. In cardiac and skeletal muscle cotransplants, the inflammation was restricted to cardiac tissue; however, by 30 days the entire cotransplant was filled with regenerated myotubes and myofibers. These results show that skeletal muscle is capable of growth, regeneration, and integration with the cardiac muscle after cotransplantation. Combination of skeletal and cardiac muscle may prove useful in defining the cellular processes necessary for enhancing cardiac repair after injury.

Whole skeletal muscle transplantation: Mechanisms responsible for functional deficits

One aspect of tissue engineering of skeletal muscle involves the transposition and transplantation of whole muscles to treat muscles damaged by injury or disease. The transposition of whole muscles has been used for many decades, but since 1970, the development of techniques for microneurovascular repair has allowed the transplantation of muscles invariably result in structural and functional deficits. The deficits are of the greatest magnitude during the first month, and then a gradual recovery results in the stabilization of structural and functional variables between 90 and 120 days. In stabilized vascularized grafts ranging from 1 to 3 g in rats to 90 g in dogs, the major deficits are approximately 25% decrease in muscle mass and in most grafts approximately 40% decrease in maximum force. The decrease in power is more complex because it depends on both the average shortening force and the velocity of shortening. As a consequence, the deficit in maximum power may be either greater or less than the deficit in maximum force. Tenotomy and repair are the major factors responsible for the deficits.Although the data are limited, skeletal muscle grafts appear to respond to training stimuli in a manner no different from that of control muscles. The training stimuli include traditional methods of endurance and strength training, as well as chronic electrical stimulation. Transposed and transplanted muscles develop sufficient force and power to function effectively to: maintain posture; move limbs; sustain the patency of sphincters; partially restore symmetry in the face; or serve as, or drive, assist devices in parallel or in series with the heart.

Free skeletal muscle transplantation to an infarction area: an experimental study in the dog.

In plastic surgery, free skeletal muscle flaps are used for treatment of non-healing injuries like chronic osteitis or radiation ulcers. We wanted to evaluate if the neoangiogenesis induced by these flaps can also constitute a method for revascularization in ischemic heart disease. In diffuse small vessel coronary heart disease, patients are not suitable for bypass surgery because it is impossible to create a microanastomosis with the coronary artery. As an alternative, a free striated muscle flap, transplanted onto the heart, can constitute a source of neovessels. With the induction of extra-intracardial collaterals that develop within 4 weeks after transplantation of the flap, a new surgical approach may be offered to those patients. Our experimental work was performed with 20 dogs. In these, a myocardial infarction of the anterior wall was selectively produced using the Judkins-technique (Radiology 89: 815-824, 1967) for injection of Sephadex-microspheres. Four weeks later a free pectoralis muscle flap was transplanted onto the anterior wall of the heart. Arterial blood supply was achieved with an anastomosis with the internal mammary artery. The venous flow was directed into the right atrium. Four to eight weeks after surgery, the patency of the anastomosis was studied by angiography, showing patency in almost all surviving animals. Histological examination of the hearts revealed a prominent vascular network penetrating into the underlying myocardium. Corrosion cast preparations, as well as a postmortem angiography, showed even further penetration of the neovessels into the uninjured parts of the myocardium. Thus, myocardial revascularization may be achieved by transplantation of a skeletal muscle onto the heart.