Combined Stem Cell and Rehabilitation Therapies for Osteoarthritis

描述：骨关节炎（OA）是一种使关节关节衰弱的疾病。关节炎是第三大流行病 退伍军人群体的健康问题影响了43%的VA系统用户，退伍军人的健康问题可能性高出36%。 与普通人群相比，该提案将利用临床前模型， 骨关节炎和测试再生干细胞疗法与康复相结合的疗效 养生法这项研究的总体目标是检查软骨退变的进展 以及在有和没有治疗剂的对比负荷条件下功能能力的变化 在大鼠中使用良好建立的损伤/手术诱导的膝关节OA模型观察MSC的益处。我们的整体 一种假设是，虽然关节负荷减少对软骨健康仍然有害，但关节负荷增加 反而会增强MSC在减轻创伤性膝关节损伤后PTOA方面的治疗效果。 研究计划：为了实现上述目标，我们制定了两个目标：目标1：{确定效果 通过非负重或跑步改变膝关节负荷，软骨退化，关节运动学， 运动，和自主活动程度的大鼠后，内侧小脑横断（MMT）手术。目的 2：检查膝关节负荷改变（通过非负重或跑步）如何影响MSC的疗效 对大鼠的软骨变性、运动期间的关节运动学和随意活动程度的治疗 根据MMT。 方法：采用MMT诱导的大鼠OA模型。同种异体MSC或盐水（对照）将被移植到骨髓中。 在手术后一天通过关节内注射施用，以评估对OA发作的影响（目的1）。 然后将两个注射组中的大鼠随机分配至以下3种负荷条件： 负荷，2）通过后肢悬吊的非负重，和3）每天跑步机跑步。将对大鼠进行测试， 在损伤后第8周结束时处死，以评估3D显微结构和组成的变化， 使用我们先前开发的EPIC-µCT扫描膝关节软骨，并进行组织学验证。评估 在手术前和手术后2、4、6和8周评价大鼠的功能能力。在每个时间 在这一点上，我们将通过量化跑步的数量（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，髋关节、膝关节和踝关节角度） 在跑步机运动过程中使用高速X射线运动分析系统。 我们预计，拟议的研究将导致再生康复协议的新见解， 与OA退伍军人，并将通过出版物和我们的临床顾问沟通，以影响 军人和退伍军人的关怀。

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.