Preferred M2 Polarization by ASC-Based Hydrogel Accelerated Angiogenesis and Myogenesis in Volumetric Muscle Loss Rats

Volumetric muscle loss (VML) injury resulted from massive muscle defects and diseases for which there are still no effective therapeutic treatments. This study aimed to investigate the effects of rat adipose-derived mesenchymal stem cells (rASCs) and rASCs-conditioned medium- (CM-) based type I collagen hydrogel on macrophage (MP) transition, myogenesis, and vascularization in the rat VML model. Laser Doppler results demonstrated much higher blood flow in the rASC- and CM-based hydrogel groups. qRT-PCR, hematoxylin and eosin, immunofluorescence, and Sirius Red staining manifested that both rASCs and CM-based hydrogel implantation accelerated muscle repair with upregulated angiogenesis and myogenesis, attenuated inflammation while facilitating M2 transition, and decreased the collagen deposition compared with the hydrogel group. In vitro experiments indicated that factors secreted from polarized M2 MPs could accelerate the migration and tube formation capacities of HUVECs. These results suggested that rASCs exerted immunomodulatory effects on MPs which further enhanced the proangiogenic potential on ECs to promote myogenesis and angiogenesis during muscle repair. These fundamental results support further clinical applications of ASCs for muscle loss injury.

Mitochondrial impairment induced by postnatal ActRIIB blockade does not alter function and energy status in exercising mouse glycolytic muscle in vivo

Because it leads to a rapid and massive muscle hypertrophy, postnatal blockade of the activin type IIB receptor (ActRIIB) is a promising therapeutic strategy for counteracting muscle wasting. However, the functional consequences remain very poorly documented in vivo. Here, we have investigated the impact of 8-wk ActRIIB blockade with soluble receptor (sActRIIB-Fc) on gastrocnemius muscle anatomy, energy metabolism, and force-generating capacity in wild-type mice, using totally noninvasive magnetic resonance imaging (MRI) and dynamic 31P-MRS. Compared with vehicle (PBS) control, sActRIIB-Fc treatment resulted in a dramatic increase in body weight (+29%) and muscle volume (+58%) calculated from hindlimb MR imaging, but did not alter fiber type distribution determined via myosin heavy chain isoform analysis. In resting muscle, sActRIIB-Fc treatment induced acidosis and PCr depletion, thereby suggesting reduced tissue oxygenation. During an in vivo fatiguing exercise (6-min repeated maximal isometric contraction electrically induced at 1.7 Hz), maximal and total absolute forces were larger in sActRIIB-Fc treated animals (+26 and +12%, respectively), whereas specific force and fatigue resistance were lower (−30 and −37%, respectively). Treatment with sActRIIB-Fc further decreased the maximal rate of oxidative ATP synthesis (−42%) and the oxidative capacity (−34%), but did not alter the bioenergetics status in contracting muscle. Our findings demonstrate in vivo that sActRIIB-Fc treatment increases absolute force-generating capacity and reduces mitochondrial function in glycolytic gastrocnemius muscle, but this reduction does not compromise energy status during sustained activity. Overall, these data support the clinical interest of postnatal ActRIIB blockade.

Use of Muscle Flaps in Burn Reconstruction

Electric burns are deep burns that by once-only or continuing stimulation of the nerves and striated muscles causes massive muscle contractions which can cause ruptures, ligamentous tears, fractures, and joint dislocations.High resistance of bone to the passage of electric current results in periosteal necrosis. Deep burns particularly electric burns when exposes structures valuable for important functions like joints, demands reconstructive options consisting robust viability and huge vascularity. The study was conducted in Department of plastic surgery and burn, Dhaka Medical College Hospital,Dhaka from June, 2011 to January, 2012. 18 patients were included in this series. Among them in ten patients gastrochnemius flap was applied, Lattissimus dorsi muscle flap was applied in 4 cases, Trapezius flap was applied in 2 cases and each of the other two patients were treated with Tensor fascia lata and Transverse Rectus Abdominis myocutaneous flap. Fifteen patients were adult and three patients were from paediatric age group. 88% of flaps were primarily used to cover exposed structures (bones and joints) and others were used to correct deformities. Complications include partial graft loss (3), joint stiffness(3), wound infection(1) and flap loss(1). Though these flaps are very commonly used in trauma reconstruction, their use in reconstruction in burn patients are included in this series. DOI: http://dx.doi.org/10.3329/bdjps.v4i1.18690 Bangladesh Journal of Plastic Surgery January 2013, 4(1): 29-31