Platelet rich concentrate enhances mesenchymal stem cells capacity to repair focal cartilage injury in rabbits Shani Samuel a,b , Raja Elina Ahmad a, *, Thamil Selvee Ramasamy c , Faizal Manan b , Tunku Kamarul b a Department of Physiology, Faculty of Medicine, University of Malaya, 50603, Lembah Pantai, Kuala Lumpur, Malaysia b Tissue Engineering Group (TEG), National Orthopaedic Centre of Excellence in Research and Learning (NOCERAL), Department of Orthopaedic Surgery, Faculty of Medicine, University of Malaya, 50603 Lembah Pantai, Kuala Lumpur, Malaysia c Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603, Lembah Pantai, Kuala Lumpur, Malaysia A R T I C L E I N F O Article history: Received 16 May 2017 Received in revised form 30 September 2017 Accepted 18 February 2018 Keywords: Blood Knee Regenerative medicine Platelets Growth factors Chondral defect A B S T R A C T Background: It has been previously suggested that the use of regenerative promoters, which include bone marrow-derived mesenchymal stem cells (MSCs) or natural growth factors supplement such as platelet- rich concentrate (PRC) could promote cartilage regeneration. However, the notion that the concurrent use of both promoters may provide a synergistic effect that improves the repair outcome of focal cartilage injury has not been previously demonstrated. This study was thus conducted to determine whether the concomitant use of PRC could further enhance the reparative potential of MSCs encapsulated in alginate transplanted into focal cartilage injury in rabbits. Methods: Artifically created full thickness cartilage defects were made on the weight-bearing region of medial femoral condyles in bilateral knees of New Zealand White rabbits (N = 30). After one month, the right knee was treated with either i) PRC (n = 10), ii) MSCs (n = 10), or, iii) a combination of PRC and MSCs (PRC + MSC) (n = 10), all encapsulated in alginate. The left knee remained untreated (control). Rabbits were sacrificed at 3 and 6 months after treatment. Cartilage tissue regeneration was accessed using ICRS morphologic scoring, histologic grading by O'Driscoll scoring, immunohistochemical staining and quantitative analysis of glycosaminoglycans (GAG) per total protein content. Results: At 3 months, transplantation using PRC alone was equally effective as MSCs in inducing the repair of cartilage defects. However, PRC + MSC resulted in significantly higher ICRS and O’Driscoll scores (p < 0.05) as compared to other groups. The regenerated tissues from the PRC + MSC group also had stronger staining for Safranin-O and collagen type II. By 6 months, in addition to superior ICRS and O’Driscoll scores as well as stronger staining, glycosaminoglycan per total protein content was also significantly higher (p < 0.05) in the PRC + MSC group (3.4  0.3 mg/mg) as compared to the MSC (2.6  0.2 mg/mg) or PRC (2.1  0.2 mg/mg) groups. Conclusion: PRC enhances the reparative effects of MSC in treating focal articular cartilage injuries. © 2018 Elsevier Ltd. All rights reserved. Introduction Focal injury or defect of articular cartilage is a prevalent orthopaedic problem, particularly amongst individuals participat- ing in high impact sports activities [1]. If left untreated, the initial chondral or osteochondral lesion may progress further, predis- posing the individual to early onset of osteoarthritis. Successful treatment of articular cartilage defect in the knee has continued to be a formidable challenge for clinicians, owing to the well-known poor intrinsic healing capacity of normal cartilage tissue. Nevertheless, as the knowledge of cartilage biology expands, many novel potential treatment strategies for cartilage repair have been increasingly explored in the recent years. This includes the use of regenerative promoters such as mesenchymal stem cells (MSCs) and growth factors. MSCs have been shown to promote cartilage regeneration through the production of cartilage matrix, whilst several growth factors have been shown to stimulate cartilage resident cells i.e. chondrocytes to produce repaired tissues [2]. The ability of MSCs to undergo self-renewal and multi- lineage differentiation, as well as having immunomodulatory and anti-inflammatory properties, renders them as an attractive potential therapeutic agent for tissue repair [3]. Accordingly, * Corresponding author. E-mail address: elina@ummc.edu.my (R.E. Ahmad). https://doi.org/10.1016/j.injury.2018.02.020 0020-1383/© 2018 Elsevier Ltd. All rights reserved. Injury, Int. J. Care Injured xxx (2018) xxx–xxx G Model JINJ 7597 No. of Pages 9 Please cite this article in press as: S. Samuel, et al., Platelet rich concentrate enhances mesenchymal stem cells capacity to repair focal cartilage injury in rabbits, Injury (2018), https://doi.org/10.1016/j.injury.2018.02.020 Contents lists available at ScienceDirect Injury journal homepa ge: www.elsev ier.com/locate /injury