Ganguly Payal, Fiz Nicolás, Beitia Maider, Owston Heather E, Delgado Diego, Jones Elena, Sánchez Mikel
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds LS9 7JT, UK.
Arthroscopic Surgery Unit, Hospital Vithas Vitoria, Beato Tomás de Zumarraga 10, 01008 Vitoria-Gasteiz, Spain.
J Clin Med. 2022 Jul 4;11(13):3891. doi: 10.3390/jcm11133891.
Osteoarthritis (OA) is a debilitating condition that significantly impacts its patients and is closely associated with advancing age and senescence. Treatment with autologous platelet rich plasma (PRP) is a novel approach that is increasingly being researched for its effects. Subchondral bone mesenchymal stromal cells (MSCs) are key progenitors that form bone and cartilage lineages that are affected in OA. This study investigated the changes in subchondral bone MSCs before and after combined intraosseous (IO) and intraarticular (IA) PRP infiltration. Patient bone marrow aspirates were collected from 12 patients (four male, eight female) aged 40-86 years old (median 59.5). MSCs were expanded in standard media containing human serum to passage 1 and analysed for their colony-forming potential, senescence status, and gene expression. Hip dysfunction and Osteoarthritis Outcome Score (HOOS) at baseline and 6 months post second infiltration were used to assess the clinical outcomes; seven patients were considered responders and five non-responders. The number of colony-forming MSCs did not increase in the post treatment group, however, they demonstrated significantly higher colony areas (14.5% higher compared to Pre) indicative of enhanced proliferative capacity, especially in older donors (28.2% higher). Senescence assays also suggest that older patients and responders had a higher resistance to senescent cell accumulation. Responder and non-responder MSCs tended to differ in the expression of genes associated with bone formation and cartilage turnover including osteoblast markers, matrix metalloproteinases, and their inhibitors. Taken together, our data show that in hip OA patients, combined IO and IA PRP infiltrations enhanced subchondral MSC proliferative and stress-resistance capacities, particularly in older patients. Future investigation of the potential anti-ageing effect of PRP infiltrations and the use of next-generation sequencing would contribute towards better understanding of the molecular mechanisms associated with OA in MSCs.
骨关节炎（OA）是一种使人衰弱的病症，对患者有重大影响，且与年龄增长和衰老密切相关。自体富血小板血浆（PRP）治疗是一种新型方法，其效果正得到越来越多的研究。软骨下骨间充质基质细胞（MSCs）是形成骨和软骨谱系的关键祖细胞，而这些谱系在OA中会受到影响。本研究调查了骨内（IO）和关节内（IA）联合PRP注射前后软骨下骨MSCs的变化。从12名年龄在40 - 86岁（中位数59.5岁）的患者（4名男性，8名女性）中采集骨髓抽吸物。MSCs在含人血清的标准培养基中扩增至第1代，并分析其集落形成潜力、衰老状态和基因表达。使用基线时以及第二次注射后6个月的髋关节功能障碍和骨关节炎结局评分（HOOS）来评估临床结果；7名患者被视为反应者，5名患者为无反应者。治疗后组中集落形成MSCs的数量没有增加，然而，它们显示出明显更大的集落面积（比治疗前高14.5%），表明增殖能力增强，尤其是在老年供体中（高28.2%）。衰老检测还表明，老年患者和反应者对衰老细胞积累具有更高的抵抗力。反应者和无反应者的MSCs在与骨形成和软骨周转相关的基因表达上存在差异，包括成骨细胞标志物、基质金属蛋白酶及其抑制剂。综上所述，我们的数据表明，在髋关节OA患者中，IO和IA联合PRP注射增强了软骨下MSCs的增殖和抗应激能力，尤其是在老年患者中。未来对PRP注射潜在抗衰老作用的研究以及使用下一代测序将有助于更好地理解与MSCs中OA相关的分子机制。
