Ultrasound Stimulated Chondrogenic Stem Cell Therapy for Osteoarthritis

摘要 骨关节炎是肌肉骨骼系统中最常见的退行性疾病。虽然它可以影响到任何 关节、髋关节和膝盖，骨性关节炎带来巨大的疼痛负担和行动不便。尽管进行了数十年的研究，但仍有 目前还没有临床上有效的治疗方法来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的潜力。 软骨。此外，超声(US)刺激在治疗骨性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，能对生物力学刺激的合成代谢做出反应。因此，我们 假设干细胞和US的联合使用将在治疗骨性关节炎方面产生协同反应。这一假设 将在三个具体目标上进行测试。在第一个目的中，我们比较了两种不同的茎向软骨分化的情况。 细胞来源，间充质细胞和脂肪细胞，使用体外3D培养和US暴露时间。在第二个目标中，我们将 将来自AIM 1的最佳超声增强的软骨形成细胞植入人关节软骨缺损处，体外和 比较脉冲式和连续式超声。最后，在第三个目标中，我们将测试优化的US增强 软骨性透明质酸水凝胶包裹细胞体内使用骨关节炎大鼠模型。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，可以修复软骨组织，逆转骨关节炎 进展，并显著减轻骨性关节炎疼痛fi。

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.