Regenerative Therapies for Equine Degenerative Joint Disease: A Preliminary Study

被引:89
作者
Broeckx, Sarah [1 ]
Zimmerman, Marieke [2 ]
Crocetti, Sara [3 ]
Suls, Marc [2 ]
Marien, Tom [4 ]
Ferguson, Stephen J. [3 ,5 ]
Chiers, Koen [6 ]
Duchateau, Luc [7 ]
Franco-Obregon, Alfredo [3 ,5 ,8 ]
Wuertz, Karin [3 ,5 ]
Spaas, Jan H. [1 ]
机构
[1] Global Stem Cell Technol, Meldert Lummen, Belgium
[2] Equine Vet Practice Dr Suls, Weert, Netherlands
[3] ETH, Dept Biomech, Zurich, Switzerland
[4] Equitom Equine Hosp, Meldert Lummen, Belgium
[5] Univ Zurich, Competence Ctr Appl Biotechnol & Mol Med CABMM, Zurich, Switzerland
[6] Univ Ghent, Fac Vet Med, Dept Pathol Bacteriol & Poultry Dis, Merelbeke, Belgium
[7] Univ Ghent, Fac Vet Med, Dept Comparat Physiol & Biometr, Merelbeke, Belgium
[8] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Surg, Singapore 117595, Singapore
关键词
MESENCHYMAL STEM-CELLS; PLATELET-RICH PLASMA; STROMAL CELLS; BONE-MARROW; TENDON; DIFFERENTIATION; MULTIPOTENT; HORSE; P63;
D O I
10.1371/journal.pone.0085917
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
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 (T-1), 12 weeks (T-2), 6 months (T-3) and 12 months (T-4) 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 T-1. 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.
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页数:11
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