ORIGINAL ARTICLE Laboratory science Experimental study on the role of intra-articular injection of MSCs on cartilage regeneration in haemophilia R. RAVANBOD,* G. TORKAMAN,* M. MOPHID † and F. MOHAMMADALI ‡ *Department of Physical Therapy, Biomechanical Research Laboratory, Tarbiat Modares University; †Department of Histology, Baquiyatallah University of Medical Sciences; and ‡Department of Hematology, Tarbiat Modares University, Tehran, Iran Summary. Mesenchymal stem cells (MSCs) therapy is a field in progress in cartilage repair strategies. We tried to investigate the functional properties of the joint and cartilage in experimental haemarthrosis (EH) after MSCs intra-articular (IA) injection. One millilitre of fresh autologous blood was injected twice a week for three consecutive weeks in three groups including control haemophilia 10 days (n = 8), control haemophilia 38 days (n = 8) and MSCs (n = 8) group. In later, 10 days after the end of IA blood injections, MSCs IA injection was performed. Eight animals received no treatment as the normal control group. Thirty-eight days after the end of IA blood injections, animals were sacrificed. Joint friction and stress- relaxation tests were done, inflammatory cytokines of synovial membrane and scanning electron microscopy of the cartilage assessed. Joint friction decreased in MSCs in comparison to other groups and was significant with normal control group, (P = 0.011). The mechanical properties of cartilage showed no significant differences between groups. Tumour necrosis factor alpha and interleukin 1 beta decreased and IL-4 very slightly increased in MSCs in comparison to the time-matched control group. Scanning electron microscopy enabled acquisition of good structural properties of the surface and layers of the cartilage after MSCs injection. The hole induced in the medial plateau of the tibia bones, after inducing haemarthrosis, were covered with cartilage-like structure. The results showed that MSCs IA injection has some beneficial effects on cartilage structure and function in haemarthrosis model and is promising in patients with haemophilia. Keywords: articular cartilage, biomechanics, friction, haemarthrosis, knee joint, mesenchymal stem cell Introduction Decades ago, lack of prophylaxis made patients with haemophilia (PWH) experience massive bleedings and compelled them to tackle intensive on-demand therapy until reminiscence of haemarthroses. Nowadays, despite prophylactic treatment, chronic microhaemor- rhages into the joint or subchondral bone, the influ- ence of different gene defect on haemarthrosis phenotype, disturbed cartilage loading and other unknown aetiologies could induce silent synovitis and cartilage degeneration [1–3]. Not a rare occurrence of very mild synovitis in the shed of prophylaxis regi- mens, particularly low-dose prophylaxis, could silently destroy the joints in later life. The term of sports or trauma-induced arthropathy is common as replace- ment therapy of clotting factors makes PWH live a more normal life [4,5]. Therefore, the need of invasive procedures like joint arthroplasty is still a predicament both in developing countries with low factor con- sumption per capita and also in developed countries. There are surgical methods to restore synovial joint function in osteoarthritis (OA). Arthroscopic debridement, microfracture, mosaicplasty, autologous chondrocyte transplantation (ACT) and tissue-engi- neered-based constructs have been implemented [6,7]. However, only limited reports are available for joint debridement in haemophilic arthropathy (HA) [8–11]. The drawbacks of cartilage methods are the paucity of the cell source [12], different mechanical environ- ments of the cartilage harvested from a non-weight- bearing area being transferred to a culture medium and finally implanted to a weight-bearing area [13], chondrocytes dedifferentiation and hypertrophy, lack of adhesion to the host tissue [14,15] and principally Correspondence: Giti Torkaman, Faculty of Medical Sciences, Tarbiat Modares University, Across Chamran and Jalal-al-Ahmad Highways, Tehran 14115-331, Iran. Tel: +98 21 82884509; fax: +98 21 88013030; e-mail: torkamg@modares.ac.ir Accepted after revision 21 January 2015 © 2015 John Wiley & Sons Ltd 693 Haemophilia (2015), 21, 693–701 DOI: 10.1111/hae.12659