methylcellulose and Cicatrix

Treatment of chronic spinal cord injury (SCI) is challenging due to cell loss, cyst formation, and the glial scar. Previously, we reported on the therapeutic potential of a neural progenitor cell (NPC) and chondroitinase ABC (ChABC) combinatorial therapy for chronic SCI. However, the source of NPCs and delivery system required for ChABC remained barriers to clinical application. Here, we investigated directly reprogrammed human NPCs biased toward an oligodendrogenic fate (oNPCs) in combination with sustained delivery of ChABC using an innovative affinity release strategy in a crosslinked methylcellulose biomaterial for the treatment of chronic SCI in an immunodeficient rat model. This combinatorial therapy increased long-term survival of oNPCs around the lesion epicenter, facilitated greater oligodendrocyte differentiation, remyelination of the spared axons by engrafted oNPCs, enhanced synaptic connectivity with anterior horn cells and neurobehavioral recovery. This combinatorial therapy is a promising strategy to regenerate the chronically injured spinal cord.

Topics: Animals; Anterior Horn Cells; Axons; Cell Differentiation; Cell Lineage; Cell Survival; Chondroitin ABC Lyase; Chondroitin Sulfate Proteoglycans; Chronic Disease; Cicatrix; Cross-Linking Reagents; Female; Humans; Methylcellulose; Motor Activity; Neural Stem Cells; Neuralgia; Neuronal Plasticity; Oligodendroglia; Rats; Recovery of Function; Remyelination; Spinal Cord Injuries; Synapses

The authors investigated the feasibility of using injectable hydrogels, based on poly(N-isopropylacrylamide) (PNIPAAm), lightly cross-linked with polyethylene glycol (PEG) or methylcellulose (MC), to serve as injectable scaffolds for local delivery of neurotrophins and cellular transplants into the injured spinal cord. The primary aims of this work were to assess the biocompatibility of the scaffolds by evaluating graft cell survival and the host tissue immune response. The scaffolds were also evaluated for their ability to promote axonal growth through the action of released brain-derived neurotrophic factor (BDNF).. The in vivo performance of PNIPAAm-g-PEG and PNIPAAm-g-MC was evaluated using a rodent model of spinal cord injury (SCI). The hydrogels were injected as viscous liquids into the injury site and formed space-filling hydrogels. The host immune response and biocompatibility of the scaffolds were evaluated at 2 weeks by histological and fluorescent immunohistochemical analysis. Commercially available matrices were used as a control and examined for comparison.. Experiments showed that the scaffolds did not contribute to an injury-related inflammatory response. PNIPAAm-g-PEG was also shown to be an effective vehicle for delivery of cellular transplants and supported graft survival. Additionally, PNIPAAm-g-PEG and PNIPAAm-g-MC are permissive to axonal growth and can serve as injectable scaffolds for local delivery of BDNF.. Based on the results, the authors suggest that these copolymers are feasible injectable scaffolds for cell grafting into the injured spinal cord and for delivery of therapeutic factors.

Topics: Acrylamides; Acrylic Resins; Animals; Axons; Brain-Derived Neurotrophic Factor; Cell Transplantation; Cicatrix; Disease Models, Animal; Drug Delivery Systems; Female; Graft Survival; Hydrogels; Injections, Intralesional; Methylcellulose; Nerve Regeneration; Neuroglia; Pilot Projects; Polyethylene Glycols; Polymers; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries; Tissue Scaffolds

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