Broeckx Sarah, Zimmerman Marieke, Crocetti Sara, Suls Marc, Mariën Tom, Ferguson Stephen J, Chiers Koen, Duchateau Luc, Franco-Obregón Alfredo, Wuertz Karin, Spaas Jan H
Global Stem cell Technology, Meldert-Lummen, Belgium.
Equine Veterinary Practice Dr Suls, Weert, The Netherlands.
PLoS One. 2014 Jan 20;9(1):e85917. doi: 10.1371/journal.pone.0085917. eCollection 2014.
Degenerative joint disease (DJD) is a major cause of reduced athletic function and retirement in equine performers. For this reason, regenerative therapies for DJD have gained increasing interest. Platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) were isolated from a 6-year-old donor horse. MSCs were either used in their native state or after chondrogenic induction. In an initial study, 20 horses with naturally occurring DJD in the fetlock joint were divided in 4 groups and injected with the following: 1) PRP; 2) MSCs; 3) MSCs and PRP; or 4) chondrogenic induced MSCs and PRP. The horses were then evaluated by means of a clinical scoring system after 6 weeks (T1), 12 weeks (T2), 6 months (T3) and 12 months (T4) post injection. In a second study, 30 horses with the same medical background were randomly assigned to one of the two combination therapies and evaluated at T1. The protein expression profile of native MSCs was found to be negative for major histocompatibility (MHC) II and p63, low in MHC I and positive for Ki67, collagen type II (Col II) and Vimentin. Chondrogenic induction resulted in increased mRNA expression of aggrecan, Col II and cartilage oligomeric matrix protein (COMP) as well as in increased protein expression of p63 and glycosaminoglycan, but in decreased protein expression of Ki67. The combined use of PRP and MSCs significantly improved the functionality and sustainability of damaged joints from 6 weeks until 12 months after treatment, compared to PRP treatment alone. The highest short-term clinical evolution scores were obtained with chondrogenic induced MSCs and PRP. This study reports successful in vitro chondrogenic induction of equine MSCs. In vivo application of (induced) MSCs together with PRP in horses suffering from DJD in the fetlock joint resulted in a significant clinical improvement until 12 months after treatment.
退行性关节病（DJD）是导致马匹运动员运动功能下降和退役的主要原因。因此，针对DJD的再生疗法越来越受到关注。从一匹6岁的供体马中分离出富血小板血浆（PRP）和间充质干细胞（MSCs）。MSCs要么以其天然状态使用，要么在软骨诱导后使用。在一项初步研究中，将20匹患有自然发生的跗关节DJD的马分为4组，并注射以下物质：1）PRP；2）MSCs；3）MSCs和PRP；或4）软骨诱导的MSCs和PRP。然后在注射后6周（T1）、12周（T2）、6个月（T3）和12个月（T4）通过临床评分系统对马进行评估。在第二项研究中，将30匹具有相同医学背景的马随机分配到两种联合疗法之一，并在T1进行评估。发现天然MSCs的蛋白质表达谱对主要组织相容性（MHC）II和p63呈阴性，MHC I水平低，对Ki67、II型胶原蛋白（Col II）和波形蛋白呈阳性。软骨诱导导致聚集蛋白聚糖、Col II和软骨寡聚基质蛋白（COMP）的mRNA表达增加，以及p63和糖胺聚糖的蛋白质表达增加，但Ki67的蛋白质表达减少。与单独使用PRP治疗相比，PRP和MSCs的联合使用在治疗后6周直至12个月显著改善了受损关节的功能和可持续性。软骨诱导的MSCs和PRP获得了最高的短期临床进展评分。本研究报告了马MSCs在体外成功的软骨诱导。在患有跗关节DJD的马体内应用（诱导的）MSCs与PRP一起，直到治疗后12个月临床有显著改善。
