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; 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.

抽象的 骨关节炎（OA）是肌肉骨骼系统中最常见的退行性疾病。虽然它会影响任何 OA关节，髋关节和膝盖带有巨大的疼痛和迁移率降低。尽管进行了数十年的研究，但 目前尚无临床有效的治疗方法可以修复损坏的软骨或停止该疾病的进展。 但是，组织再生的最新进展表明，干细胞疗法有可能修复受损的 软骨。此外，超声（US）刺激还显示出令人鼓舞的结果在处理OA符号方面。这是 因为软骨是一种机械转导的组织，对生物力学刺激反应了合成代谢。因此，我们 假设干细胞和美国的联合使用将在治疗OA时具有协同反应。这个假设 将以三个特定目标进行测试。在第一个目标中，我们比较了两个不同茎的软骨差分 使用体外3D培养和美国暴露时间，细胞来源，间质和脂肪。在第二个目标中，我们将 将AIM 1的最佳美国增强软骨细胞植入人类关节软骨缺陷，离体和 比较脉冲与连续超声。最后，在第三个目标中，我们将测试优化的美国增强物 软骨基水凝胶使用OA大鼠模型在体内包裹了细胞。这些研究将使我们能够 开发一种新的超声诱导的软骨干细胞疗法，该疗法可以修复软骨组织，将回归OA 进展，并显着减少骨关节炎疼痛。