Osteoarthritis (OA) is the most common degenerative disease in the musculoskeletal system. While it can affect any joint, hip, and knee, OA carries an enormous burden of pain and reduced mobility. Despite decades of research, there are currently no clinically effective treatments that can repair damaged cartilage or halt the progression of this disease. However, recent advances in tissue regeneration show that stem cell therapy has the potential to repair damaged cartilage. In addition, ultrasound (US) stimulation has also shown encouraging results in treating OA symptoms. This is because cartilage is a mechanotransductive tissue that responds anabolic to biomechanical stimuli. Therefore, we hypothesize that the combined use of stem cells and US will have a synergistic response in treating OA. This hypothesis will be tested in three specific aims. In the first aim, we compare the chondrogenic differentiation of two different stem cell sources, mesenchymal and adipose, using in vitro 3D culture and US exposure time period. In the second aim, we will implant the optimal US-enhanced chondrogenic cells from Aim 1 in human articular cartilage defects, ex vivo, and compare pulsed to continuous ultrasound. Finally, in the third aim, we will test the optimized US-enhanced chondrogenic hyaluronic hydrogel encapsulated cell in vivo using an OA rat model. These studies will allow us to develop a new ultrasound-induced chondrogenic stem cell therapy that can repair cartilage tissue, regress the OA progression, and reduce osteoarthritic pain signiï¬cantly.
Public Health Relevance Statement: Narrative Osteoarthritis is a debilitating disease that affects an enormous number of people. No treatments other than arthroplasty have been developed to stop its progression, reduce pain, and increase range of motion. This proposal seeks to combine the use of hydrogel ,stem cells, and ultrasound therapy to develop a new treatment for osteoarthritis. These approaches have shown some promise alone and their combination will pave the way for a new therapy to reduce OA-associated pain and improve mobility. Importantly, these experiments have been designed to facilitate a rapid proof-of-concept to pave the way for future clinical studies.
Project Terms: Fatty Tissue; adipose; white adipose tissue; yellow adipose tissue; Adipose tissue; Affect; After Care; After-Treatment; post treatment; Aftercare; Arthritis; arthritic; Biological Assay; Assay; Bioassay; Biologic Assays; Biomechanics; biomechanical; Cartilage; Cartilaginous Tissue; articular cartilage; Cells; Cell Body; Clinical Research; Clinical Study; Clinical Trials; Disease; Disorder; Environment; Fatigue; Lack of Energy; Flow Cytometry; Flow Cytofluorometries; Flow Cytofluorometry; Flow Microfluorimetry; Flow Microfluorometry; flow cytophotometry; Future; Gait; Hip region structure; Coxa; Hip; Histology; Human; Modern Man; Hyaluronic Acid; In Vitro; Joints; Knee; Musculoskeletal System; locomotor system; Persons; Degenerative polyarthritis; Degenerative Arthritis; Osteoarthritis; Osteoarthrosis; degenerative joint disease; hypertrophic arthritis; osteoarthritic; Pain; Painful; Patients; Nude Rats; Athymic Rats; Rattus; Common Rat Strains; Rat; Rats Mammals; Natural regeneration; Regeneration; regenerate; Research; stem cells; Progenitor Cells; Synovial Fluid; Synovia; Testing; Time; Tissues; Body Tissues; Ultrasonic Therapy; ultrasound energy; ultrasound therapy; Viscosity; Articular Range of Motion; Joint Range of Motion; range of motion; Knee arthroplasty; Knee joint replacement operation; Knee replacement; Total Knee Replacement; total knee arthroplasty; knee replacement arthroplasty; Arthroplasty; Joint Prosthesis Implantation; joint arthroplasty; joint replacement; Replacement Arthroplasty; Clinical; Encapsulated; repair; repaired; Phase; Histologically; Histologic; Meniscus; Meniscus structure of joint; disability; Stimulus; Hypoxic; Oxygen Deficiency; Hypoxia; Disease Progression; Exposure to; Specimen; Research Specimen; Physiologic pulse; Pulse; Source; 3-Dimensional; 3-D; 3D; three dimensional; Operative Surgical Procedures; Operative Procedures; Surgical; Surgical Interventions; Surgical Procedure; surgery; Animal Model; Animal Models and Related Studies; model of animal; Hydrogels; Modality; genetic analysis; Genetic analyses; Modeling; Sampling; response; stem cell therapy; stem cell based therapy; stem cell mediated therapy; stem cell therapeutics; stem cell treatment; stem cell-based treatment; cartilage repair; Mesenchymal Progenitor Cell; Mesenchymal progenitor; Mesenchymal Stem Cells; degenerative condition; degenerative disease; Degenerative Disorder; Defect; Symptoms; Direct Costs; Mesenchymal; Proliferating; in vivo; Facilities and Administrative Costs; Indirect Costs; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Molecular; symptom management; manage symptom; tissue regeneration; regenerate new tissue; regenerate tissue; regenerating damaged tissue; regenerating tissue; tissue regrowth; tissue renewal; tissue specific regeneration; cartilage regeneration; cost; designing; design; determine efficacy; efficacy analysis; efficacy assessment; efficacy determination; efficacy examination; evaluate efficacy; examine efficacy; efficacy evaluation; Outcome; Implant; new drug treatments; new drugs; new pharmacological therapeutic; new therapeutics; new therapy; next generation therapeutics; novel drug treatments; novel drugs; novel pharmaco-therapeutic; novel pharmacological therapeutic; novel therapy; novel therapeutics; improve function; improved functional outcomes; functional improvement; effective treatment; effective therapy; regenerative; mobility enhancement; mobility improvement; optimized mobility; improved mobility; treatment group; 3D cell culture; 3D culture; three dimensional cell culture; 3-D ultrasound; 3D ultrasound; experiment; experimental research; experiments; experimental study; reduce pain; pain reduction; osteoarthritis associated pain; osteoarthritis pain; ultrasound; adipose derived stem cell; adipose stem cell
