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.

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。虽然它可以影响任何 关节、髋部和膝部，OA 带来巨大的疼痛负担和活动能力下降。尽管经过数十年的研究， 目前尚无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，组织再生的最新进展表明，干细胞疗法具有修复受损组织的潜力。 软骨。此外，超声（US）刺激在治疗骨关节炎症状方面也显示出令人鼓舞的效果。这是 因为软骨是一种机械传导组织，对生物力学刺激作出合成代谢反应。因此，我们 假设干细胞和超声的联合使用将在治疗 OA 方面产生协同效应。这个假设 将在三个具体目标上进行测试。在第一个目标中，我们比较两种不同干细胞的软骨形成分化 细胞来源，间充质和脂肪，使用体外 3D 培养和美国暴露时间段。在第二个目标中，我们将 将来自目标 1 的最佳超声增强软骨细胞离体植入人类关节软骨缺陷中，并 比较脉冲超声波和连续超声波。最后，在第三个目标中，我们将测试优化后的US-enhanced 使用 OA 大鼠模型体内软骨形成透明质酸水凝胶封装细胞。这些研究将使我们能够 开发一种新的超声诱导软骨干细胞疗法，可以修复软骨组织，使骨关节炎消退 进展，并显着减轻骨关节炎疼痛。