Ultrasound Stimulated Chondrogenic Stem Cell Therapy for Osteoarthritis

超声刺激软骨干细胞治疗骨关节炎

• 批准号: 10701506
• 负责人: Suresh Anaganti
• 金额: $ 31.93万
• 依托单位: LAB TO PHARMACY LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-22 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10701506
• 关键词: 3-Dimensional; 3D ultrasound; Adipose tissue; Affect; Aftercare; Animal Model; Arthritis; Articular Range of Motion; Biological Assay; Biomechanics; Cartilage; Cells; Clinical; Clinical Research; Clinical Trials; Defect; Degenerative Disorder; Degenerative polyarthritis; Direct Costs; Disease; Disease Progression; Encapsulated; Environment; Exposure to; Facilities and Administrative Costs; Fatigue; Flow Cytometry; Future; Gait; Hip region structure; Histologic; Histology; Human; Hyaluronic Acid; Hydrogels; Hypoxia; Implant; In Vitro; Joints; Knee; Meniscus structure of joint; Mesenchymal; Mesenchymal Stem Cells; Modality; Modeling; Molecular; Musculoskeletal System; Natural regeneration; Nude Rats; Operative Surgical Procedures; Outcome; Pain; Patients; Persons; Phase; Physiologic pulse; Proliferating; Rattus; Replacement Arthroplasty; Research; Sampling; Small Business Innovation Research Grant; Source; Specimen; Stimulus; Symptoms; Synovial Fluid; Testing; Time; Tissues; Ultrasonic Therapy; Viscosity; adipose derived stem cell; articular cartilage; cartilage regeneration; cartilage repair; cost; design; disability; effective therapy; efficacy evaluation; experimental study; functional improvement; genetic analysis; improved mobility; in vivo; knee replacement arthroplasty; novel therapeutics; osteoarthritis pain; pain reduction; regenerative; repaired; response; stem cell therapy; stem cells; symptom management; three dimensional cell culture; tissue regeneration; treatment group; ultrasound

Abstract 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 significantly.

摘要