Combined Stem Cell and Rehabilitation Therapies for Osteoarthritis

骨关节炎的干细胞与康复疗法相结合

• 批准号: 9350659
• 负责人: Nick J Willett
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9350659
• 关键词: Activities of Daily Living; Address; Adult; Affect; Age; Allogenic; Animal Model; Ankle; Anti-Inflammatory Agents; Anti-inflammatory; Arthritis; Attenuated; Caring; Cartilage; Cell Differentiation process; Clinical; Consultations; Degenerative polyarthritis; Development; Disease; Evaluation; Exercise; Family; Fluoroscopy; Foundations; General Population; Goals; Growth Factor; Guidelines; Health; Healthcare; Hindlimb Suspension; Hip region structure; Histology; Histopathology; Image; Immunohistochemistry; Incidence; Injection of therapeutic agent; Injury; Intervention; Intra-Articular Injections; Joints; Knee; Knee Injuries; Knee Osteoarthritis; Knee joint; Knowledge; Left; Limb structure; Locomotion; Lower Extremity; Mechanical Stimulation; Medial; Medical; Mesenchymal Stem Cells; Methods; Military Personnel; Modeling; Motion; Movement; Operative Surgical Procedures; Outcome; Patient-Focused Outcomes; Patients; Pattern; Physical therapy; Population; Pre-Clinical Model; Protocols documentation; Publications; Quality of life; Randomized; Rattus; Recovery of Function; Regenerative Medicine; Regimen; Rehabilitation therapy; Research; Risk; Roentgen Rays; Running; Saline; Shock; Speed; Stem cells; Suspensions; System; Systems Analysis; Techniques; Testing; Therapeutic; Therapeutic Effect; Time; Veterans; Work; absorption; articular cartilage; cartilage degradation; contrast enhanced; daily functioning; design; disability; efficacy testing; functional outcomes; high risk; improved; innovation; insight; joint loading; kinematics; male; paracrine; physical therapist; regenerative; regenerative therapy; response; service member; stem cell therapy; successful intervention; survivorship; tomography; treadmill; Activities of Daily Living; Address; Adult; Affect; Age; Allogenic; Animal Model; Ankle; Anti-Inflammatory Agents; Anti-inflammatory; Arthritis; Attenuated; Caring; Cartilage; Cell Differentiation process; Clinical; Consultations; Degenerative polyarthritis; Development; Disease; Evaluation; Exercise; Family; Fluoroscopy; Foundations; General Population; Goals; Growth Factor; Guidelines; Health; Healthcare; Hindlimb Suspension; Hip region structure; Histology; Histopathology; Image; Immunohistochemistry; Incidence; Injection of therapeutic agent; Injury; Intervention; Intra-Articular Injections; Joints; Knee; Knee Injuries; Knee Osteoarthritis; Knee joint; Knowledge; Left; Limb structure; Locomotion; Lower Extremity; Mechanical Stimulation; Medial; Medical; Mesenchymal Stem Cells; Methods; Military Personnel; Modeling; Motion; Movement; Operative Surgical Procedures; Outcome; Patient-Focused Outcomes; Patients; Pattern; Physical therapy; Population; Pre-Clinical Model; Protocols documentation; Publications; Quality of life; Randomized; Rattus; Recovery of Function; Regenerative Medicine; Regimen; Rehabilitation therapy; Research; Risk; Roentgen Rays; Running; Saline; Shock; Speed; Stem cells; Suspensions; System; Systems Analysis; Techniques; Testing; Therapeutic; Therapeutic Effect; Time; Veterans; Work; absorption; articular cartilage; cartilage degradation; contrast enhanced; daily functioning; design; disability; efficacy testing; functional outcomes; high risk; improved; innovation; insight; joint loading; kinematics; male; paracrine; physical therapist; regenerative; regenerative therapy; response; service member; stem cell therapy; successful intervention; survivorship; tomography; treadmill

Description: Osteoarthritis (OA) is a debilitating condition of articular joints. Arthritis is the 3rd most prevalent health problem in the Veterans population affecting 43% of VA system users and veterans are ~36% more likely to be affected by OA as compared to the general population. This proposal will utilize preclinical models of osteoarthritis and test the efficacy of regenerative stem cell therapies in combination with rehabilitation regimens. The overall objective of the proposed study is to examine the progression of cartilage degeneration and changes in functional capacities under contrasting loading conditions with and without the therapeutic benefits of MSCs using a well-established injury/surgery induced knee OA model in rats. Our overall hypothesis is that while reduced joint loading will remain detrimental to cartilage health, an elevated joint load will instead enhance the therapeutic effects of MSCs on attenuating PTOA following traumatic knee injuries. Research Plan: To address the above objective we have developed two aims: Aim 1: {To establish the effects of altered knee loading via non-weight bearing or running on cartilage degeneration, joint kinematics during locomotion, and degree of voluntary activity in rats following a medial meniscal transection (MMT) surgery. Aim 2: To examine how altered knee loading (via non-weight bearing or running) influences the efficacy of MSC treatment on cartilage degeneration, joint kinematics during locomotion, and degree of voluntary activity in rats following MMT.} Methods: The rat MMT-induced OA model will be used for this study. Allogeneic MSCs or saline (control) will be administered via intra-articular injection one day post-surgery to assess the effects on the onset of OA (Aim 1). Rats in both injection groups will then be randomly assigned to the following 3 loading conditions: 1) regular loading, 2) non-weight bearing via hind limb suspension, and 3) daily treadmill running. Rats will be tested and sacrificed at the end of the 8th week post-injury to assess the changes in 3D microstructure and composition in the knee articular cartilage using our previously developed EPIC-µCT and validated with histology. To assess functional capacities rats will be evaluated at pre-surgery and 2, 4, 6, and 8 weeks post-surgery. At each time point, we will assess the level of voluntary activity by quantifying the amount (time and distance) of running on a wheel mounted inside the cage. We will quantify 3D lower limb kinematics (i.e., hip, knee, and ankle angles) during treadmill locomotion using a high-speed X-ray motion analysis system. We anticipate the proposed research will result in new insights on regenerative rehabilitation protocols for veterans with OA and will be communicated through publications and our clinical consultants in order to impact military and Veterans care.

描述：骨关节炎（OA）是关节关节的令人衰弱的疾病。关节炎是第三最普遍的 在影响43％的VA系统使用者和退伍军人的退伍军人人口中，健康问题的可能性高约36％ 与普通人群相比，会受到OA的影响。该建议将利用 骨关节炎并测试再生干细胞疗法与康复的效率 方案。拟议的研究的总体目的是检查软骨变性的进展 以及在有和不进行治疗的对比载荷条件下功能能力的变化 使用公认的损伤/手术诱导大鼠膝关节模型的MSC的好处。我们的整体 假设是，虽然减少的关节负载将仍然不利于软骨健康，但关节负荷升高 相反，将增强MSC在膝盖受伤后衰减PTOA的治疗作用。 研究计划：为了解决上述目标，我们开发了两个目标：目标1：{确定效果 通过非重量轴承或在软骨变性上跑步的膝盖负荷改变的膝关节负荷，关节运动学 半月板转导（MMT）手术后大鼠的运动和自愿活动程度。目的 2：检查膝关节负荷发生变化（通过非重量轴承或跑步）如何影响MSC的效率 在软骨变性，运动过程中的关节运动学以及大鼠的自愿活动程度的治疗 遵循MMT。} 方法：将使用大鼠MMT诱导的OA模型进行本研究。同种异体MSC或盐水（对照）将是 通过关节内注射在手术后通过关节内注射来评估对OA发作的影响（AIM 1）。 然后，两个注射组中的大鼠将随机分配到以下3个加载条件：1）常规 加载，2）通过后肢悬架进行非重量轴承，3）每日跑步机。大鼠将进行测试， 在伤害后第8周结束时牺牲，以评估3D微结构和组成的变化 使用我们先前开发的Epic-µCT并用组织学验证的膝关节软骨。评估 功能能力大鼠将在手术前和手术后2、4、6和8周评估。每次 点，我们将通过量化在A上运行的数量（时间和距离）来评估自愿活动的水平 车轮安装在笼子里。我们将量化3D下肢运动学（即臀部，膝盖和脚踝角） 在跑步机上使用高速X射线运动分析系统。 我们预计拟议的研究将导致对再生康复方案的新见解 与OA的退伍军人，将通过出版物和我们的临床顾问进行交流，以影响 军事和退伍军人关心。