SBIR-STTR Award

In the context of skeletal tissue repair, Cell Therapy is the local application of autologous (host-derived) cells to promote reconstruction of tissue defects caused by trauma, disease or surgical procedures. The objective of the Cell Therapy approach is to deliver high densities of repair-competent cells to the defect site in a format that optimizes both initial wound mechanics and eventual neotissue production. We are engaged in the development of cellular transplants and cell-matrix products for the treatment of soft tissue and bone disorders. These cellular transplants and cell-matrix products are derived from the isolation, purification and propagation of human Mesenchymal Stem Cells (MSCs), the progenitor cells which give rise to all mesodermal tissues such as cartilage, ligament, tendon and muscle. Our research will 1. demonstrate the efficacy of a proprietary cell delivery concept for autologous MSC therapy in short-term rabbit Achilles tendon implants, and 2. develop appropriate surgical techniques and perform preliminary implants for the repair of defects of the rabbit anterior cruciate ligament.Awardee's statement of the potential commercial applications of the research:ACL reconstruction represents a significant opportunity to demonstrate the promise of the cell therapy approach to soft tissue repair, while also offering the potentiat for substantial sales if a superior product can be demonstrated. Repair of Achilles tendon ruptures represents a somewhat simpler test system for extra-articular soft tissue repair and offers a more direct route for demonstrating the cell-based surgical technique.National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

The Global Hypothesis for the proposed Phase II program is that Mesenchymal Stem Cells (MSCs) can be applied to models of tendon injury to provide improved and accelerated tissue regeneration in clinically meaningful situations. In Phase II we will explore two aspects of tendon repair in areas of important clinical applications. First, we will study repair in partial and complete Achilles tendon ruptures. Second, in another model system, we will study repair of the middle one-third patellar tendon gap created when this tissue is used as a donor graft for an anterior cruciate ligament (ACL) reconstruction. The Phase l results presented in this application demonstrate the feasibility of repairing tendon defects with a novel, proprietary MSC / biomatrix construct. Statistically significant positive biomechanical results of MSCs versus controls indicate the early stiffness and strength of these regenerated tendon-like structures following implantation into a rabbit Achilles tendon defect model. Histological data provide qualitative support of these findings. At the conclusion of Phase II, we will have sufficient data to progress towards FDA approval of an IND to commence human clinical studies.Proposed commercial application:We propose to apply a unique autologous cell -based therapy (MSC) to enhance significantly the rate and quality of repair in tendons. There are several hundred thousand incidences of these clinical situations we are seeking to improve with our model systems.Thesaurus termsautologous transplantation, cell transplantation, mesenchyme, method development, nonhuman therapy evaluation, orthopedics, tendon injury biohybrid implant, cell differentiation, collagen, gel, hematopoietic stem cell, implant, joint ligament, skeletal regeneration, tendon, tissue engineering, wound healing dog, goat, histology, laboratory rabbit, tissue /cell cultureNational Institute of Arthritis and Musculosketal and Skin Diseases (NIAMS)