Russell Martin

Oleanolic acid modulates the immune-inflammatory response in mice with experimental autoimmune myocarditis and protects from cardiac injury. Therapeutic implications for the human disease

Myocarditis and dilated cardiomyopathy (DCM) are inflammatory diseases of the myocardium, for which appropriate treatment remains a major clinical challenge. Oleanolic acid (OA), a natural triterpene widely distributed in food and medicinal plants, possesses a large range of biological effects with beneficial properties for health and disease prevention. Several experimental approaches have shown its cardioprotective actions, and OA has recently been proven effective for treating Th1 cell-mediated inflammatory diseases; however, its effect on inflammatory heart disorders, including myocarditis, has not yet been addressed. Therefore, the present study was undertaken to determine the effectiveness of OA in prevention and treatment of experimental autoimmune myocarditis (EAM). The utility of OA was evaluated in vivo through their administration to cardiac α-myosin (MyHc-α614-629)-immunized BALB/c mice from day 0 or day 21 post-immunization to the end of the experiment, and in vitro through their addition to stimulated-cardiac cells. Prophylactic and therapeutic administration of OA dramatically decreased disease severity: the heart weight/body weight ratio as well as plasma levels of brain natriuretic peptide and myosin-specific autoantibodies production were significantly reduced in OA-treated EAM animals, compared with untreated ones. Histological heart analysis showed that OA-treatment diminished cell infiltration, fibrosis and dystrophic calcifications. OA also decreased proliferation of cardiac fibroblast in vitro and attenuated calcium and collagen deposition induced by relevant cytokines of active myocarditis. Furthermore, in OA-treated EAM mice the number of Treg cells and the production of IL-10 and IL-35 were markedly increased, while proinflammatory and profibrotic cytokines were significantly reduced. We demonstrate that OA ameliorates both developing and established EAM by promoting an antiinflammatory cytokine profile and by interfering with the generation of cardiac-specific autoantibodies, as well as through direct protective effects on cardiac cells. Therefore, we envision this natural product as novel helpful tool for intervention in inflammatory cardiomyopathies including myocarditis.

Signaling cue presentation and cell delivery to promote nerve regeneration.

Limitations in current nerve regeneration techniques have stimulated the development of various approaches to mimic the extrinsic cues available in the natural nerve regeneration environment. Biomaterials approaches modulate the microenvironment of a regenerating nerve through tailored presentation of signaling molecules, creating physical and biochemical guidance cues to direct axonal regrowth across nerve lesion sites. Cell-based approaches center on increasing the neurotrophic support, adhesion guidance and myelination capacity of Schwann cells and other alternative cell types to enhance nerve regrowth and functional recovery. Recent advances in presenting directional guidance cues in nerve guidance conduits and improving the regenerative outcomes of cell delivery provide inspirations to engineering the next generation of nerve repair solutions.

Local Release of Paclitaxel from Aligned, Electrospun Microfibers Promotes Axonal Extension

Traumatic spinal cord injuries ultimately result in an inhibitory environment that prevents axonal regeneration from occurring. A low concentration administration of paclitaxel has been previously shown to promote axonal extension and attenuate the upregulation of inhibitory molecules after a spinal cord injury. In this study, paclitaxel is incorporated into electrospun poly(l-lactic acid) (PLA) microfibers, and it is established that a local release of paclitaxel from aligned, electrospun microfibers promotes neurite extension in a growth-conducive and inhibitory environment. Isolated dorsal root ganglion cells are cultured for 5 d directly on tissue culture polystyrene surface, PLA film, random, or aligned electrospun PLA microfibers (1.44 ± 0.03 μm) with paclitaxel incorporated at various concentrations (0%-5.0% w/w in reference to fiber weight). To determine the effect of a local release of paclitaxel, paclitaxel-loaded microfibers are placed in CellCrown inserts above cultured neurons. Average neurite extension rate is quantified for each sample. A local release of paclitaxel maintains neuronal survival and neurite extension in a concentration-dependent manner when coupled with aligned microfibers when cultured on laminin or an inhibitory surface of aggrecan. The findings provide a targeted approach to improve axonal extension across the inhibitory environment present after a traumatic injury in the spinal cord.

Abstract P28: Nanofiber-Hydrogel Composite with Human Adipose-Derived Stem Cells to Enable Soft Tissue Regeneration

PSRC Abstract Supplement P oter P rofs transection without repair. First, we evaluated the extensor digitorum longus (EDL) muscles of 15 adult wildtype C57BL/6 mice (n=3 per time point) at days 1, 3, 5, 7, and 14 after sciatic nerve injury. The uninjured EDL muscles served as the experimental controls. These muscles were harvested for immunostaining with CD68 (monocytes/ macrophages) and DAPI (nuclear) staining. Next, using the same injury and mouse model, flow cytometry was utilized to evaluate total cells present in EDL muscle after sciatic nerve injury. Animals were sacrificed at days 1 and 5 after nerve injury, and all muscles of the hindlimb innervated by the sciatic nerve were harvested from the right injured and left uninjured legs. Cells were analyzed following muscle digestion.

An Injectable Nanofiber-Hydrogel Composite with Interfacial Bonding for Soft Tissue Filling and Regeneration.

www.PRSJournal.com 153 M oday, O cber 19 surgery ranged from 1 – 10 months (mean: 5.4 months). The mean number of secondary revisions was 3.2 per patient. The mean follow-up time from latest revision ranged from 5-47 months (mean: 20.4 months). Most interventions have consisted of debulking of soft tissues, SMAS plication and suspension, and local tissue rearrangement for contour abnormalities and excess soft tissue. There were no major infections, hematomas, skin flap loss or necrosis, and most importantly, there were no allograft losses. One patient suffered a post-operative complication after fat grafting in the form of acute rejection that resolved with pulse steroids.