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 骨关节炎（OA）是肌肉骨骼系统中最常见的退行性疾病。虽然它可以影响任何 骨关节炎对关节、髋关节和膝关节造成巨大的疼痛负担，并降低了活动能力。尽管经过几十年的研究， 目前没有临床有效的治疗方法可以修复受损的软骨或阻止这种疾病的进展。 然而，最近在组织再生方面的进展表明，干细胞疗法具有修复受损组织的潜力。 软骨此外，超声（US）刺激在治疗OA症状方面也显示出令人鼓舞的结果。这是 因为软骨是对生物力学刺激做出合成代谢反应的机械传导组织。所以我们 假设联合使用干细胞和超声在治疗OA中具有协同效应。这一假设 将在三个具体目标中进行测试。在第一个目标中，我们比较了两种不同干细胞的软骨分化， 细胞来源，间充质和脂肪，使用体外3D培养和US暴露时间段。第二个目标，我们将 将来自Aim 1的最佳US增强的软骨形成细胞植入离体人关节软骨缺损中，以及 比较脉冲超声和连续超声。最后，在第三个目标中，我们将测试优化的US增强型 软骨形成透明质酸水凝胶包封的细胞在体内使用OA大鼠模型。这些研究将使我们能够 开发一种新的超声波诱导的软骨干细胞疗法，可以修复软骨组织， 进展，并显着减少骨关节炎疼痛。