methylcellulose and Fibrosis

Stem cells therapy is an effective treatment for critical limb ischemia diseases (CLI), but is limited to low cells retention and poor target release in severe ischemia tissues. Due to the notable feature of CLI, namely, the temperature of ischemia tissues decreases with the severity of the lesions, a thermoresponsive and reversible hydrogel based on methylcellulose-salt system encapsulating stem cells is facilely prepared and successfully achieved the goal of releasing stem cells in lower temperature areas. The investigations show that the thermogel presents notable biocompatibility, thermoresponsiveness, and cytoprotection. Furthermore, the combined transplantation of hydrogel and stem cells system effectively inhibits the fibrosis and muscular atrophy of lower limb ischemia, accelerates the recovery of lower limb blood flow, and promotes angiogenesis, indicating that the reversible thermogel can promote vascular repair by controlling the release of loaded stem cells in the treatment of CLI.

Topics: Animals; Atrophy; Biopolymers; Extremities; Female; Fibrosis; HEK293 Cells; Humans; Hydrogels; Ischemia; Male; Methylcellulose; Mice; Mice, Inbred C57BL; Mice, Nude; Neovascularization, Pathologic; Neovascularization, Physiologic; Perfusion; Pregnancy; Pregnancy, Animal; Rheology; Stem Cell Transplantation; Stem Cells; Stress, Mechanical; Temperature

Systemic sclerosis (SSc) is a connective tissue disease characterized by vasculopathy, excessive accumulation of extracellular matrix, and fibrosis of the skin and internal organs. An animal model of SSc, the bleomycin-induced mouse model, has been established and used extensively to investigate the pathogenesis of SSc and to seek novel therapeutic agents. We recently developed thermo-reversible combination gels that can be injected subcutaneously and are made in aqueous solution by forming a complex coacervate with the substance of interest and cationic macromolecules, followed by co-formulation with methylcellulose (MC) as a negative thermosensitive polysaccharide. The objective of this study was to demonstrate whether weekly injections of bleomycin using combination gels loaded with bleomycin can induce the skin fibrosis model of SSc in susceptible mouse strains. A low molecular weight MC (4%) gel with 4.5% ammonium sulfate was made in aqueous solution, and mixed with bleomycin. This was injected subcutaneously into female C3H/He mice at weekly intervals. Control mice were injected with the gel made with phosphate-buffered saline. After 4 weeks, histological examination and gene expression assays of cytokines were performed. Examination in vitro showed that more than 80% of the bleomycin was released from the gel by the 4th day. Histological examination showed that dermal thickness increased in the MC-bleomycin-injected group compared with the control, and semi-quantitative analysis indicated that the extent of inflammation did not differ between the groups. In the MC-bleomycin-injected group, dermal fibrosis assessed with the Masson-Trichrome stain and numbers of alpha-smooth muscle actin-positive fibroblastic cells also increased. The procedure for inducing scleroderma in which bleomycin is injected weekly as an easily-made gel system using methylcellulose, can induce dermal fibrosis in susceptible mice without causing inflammation. We believe this system represents a time- saving and convenient procedure that should facilitate research on SSc.

Topics: Actins; Animals; Bleomycin; Cytokines; Disease Models, Animal; Drug Carriers; Female; Fibroblasts; Fibrosis; Gels; Gene Expression Regulation; Injections, Subcutaneous; Methylcellulose; Mice; Mice, Inbred C3H; Scleroderma, Systemic; Skin; Time Factors; Transforming Growth Factor beta1

The present study examined the effects of steroids and lubricants on electrical impedance and tissue response following cochlear implantation in animal models. Guinea pigs were implanted following either no treatment, or intrascalar injection with dexamethasone, triamcinolone, sodium hyaluronate or saline. Cats were implanted following either no treatment, or intrascalar injection with dexamethasone, triamcinolone or a mixture of triamcinolone with sodium hyaluronate. In guinea pigs, impedance changes and intracochlear tissue response were less for the hyaluronate and saline groups. In cats, impedance in the dexamethasone group increased similar to non-treated cats. Impedance of triamcinolone treated cats remained low for about two months after implantation, before increasing to levels similar to the other groups. Significant fibrous tissue growth was observed histologically. The results of the present study indicate that a single intracochlear application of hyaluronate or triamcinolone may postpone, but will ultimately not prevent the rise in impedance following cochlear implantation.

Topics: Animals; Cats; Cell Count; Cicatrix; Cochlea; Cochlear Implants; Dexamethasone; Electric Impedance; Electrodes, Implanted; Fibrosis; Foreign-Body Reaction; Glucocorticoids; Guinea Pigs; Hyaluronic Acid; Hypromellose Derivatives; Injections; Lubricants; Methylcellulose; Organ of Corti; Prosthesis Failure; Spiral Ganglion; Tissue Adhesions; Triamcinolone

Transforming growth factor-b2 (TGF-b2) has been implicated in the inflammatory response and subsequent scarring during wound healing.. The experiment was designed to study the effects of a topical application of TGF-b2 and mouse monoclonal anti-TGF-b2,3 neutralizing antibody (anti TGF-b2,3) on the development of fibrosis during healing.. Sixteen full-thickness excision wounds were made in the paravertebral and thoracic area of four domestic pigs. On day 0, three wounds each were treated with: a) 5 mg of TGF-b2, b) 5 mg of 2% methylcellulose (mc), or c) 1.2 mg of anti-TGF-b2,3. As a vehicle for treatment of each wound methylcellulose 2% was used. Four wounds served as the untreated air-exposed control. Wounds were biopsied and the tissue sectioned and stained with hematoxylin and eosin on days 7, 14, and 45. Three blinded observers evaluated the wound specimens.. Using computer-aided point count stereology on days 7, 14, and 45, we found a statistically significant increase (p <.05) in the number of nucleated cells in the TGF-b2-treated wounds as compared to the other control wounds. Wounds treated with anti-TGF-b2,3 had significantly (p <.05) fewer nucleated cells on days 7,14, and 45. Microscopically, the TGF-b2-treated wounds had a larger scar area as compared to anti-TGF-b2,3 and controls.. Treating wounds with an antibody directed against TGF-b2 might be a useful clinical approach to reduce fibrosis.

Topics: Administration, Topical; Animals; Antibodies, Monoclonal; Cicatrix; Fibrosis; Methylcellulose; Observer Variation; Skin; Swine; Transforming Growth Factor beta; Transforming Growth Factor beta2; Wound Healing