Transforming growth factor-beta2 (TGF-β2) is recognized as a versatile cytokine that plays a vital role in regulation of joint development, homeostasis, and diseases, but its role as a biological mechanism is understood far less than that of its counterpart, TGF-β1. Cartilage as a load-resisting structure in vertebrates however displays a fragile performance when any tissue disturbance occurs, due to its lack of blood vessels, nerves, and lymphatics. Recent reports have indicated that TGF-β2 is involved in the physiological processes of chondrocytes such as proliferation, differentiation, migration, and apoptosis, and the pathological progress of cartilage such as osteoarthritis (OA) and rheumatoid arthritis (RA). TGF-β2 also shows its potent capacity in the repair of cartilage defects by recruiting autologous mesenchymal stem cells and promoting secretion of other growth factor clusters. In addition, some pioneering studies have already considered it as a potential target in the treatment of OA and RA. This article aims to summarize the current progress of TGF-β2 in cartilage development and diseases, which might provide new cues for remodelling of cartilage defect and intervention of cartilage diseases.
The high prevalence of osteoarthritis (OA), as well as the current lack of disease-modifying drugs for OA, has provided a rationale for regenerative medicine as a possible treatment modality for OA treatment. In this editorial, the current status of regenerative medicine in OA including stem cells, exosomes, and genes is summarized along with the author’s perspectives. Despite a tremendous interest, so far there is very little evidence proving the efficacy of this modality for clinical application. As symptomatic relief is not sufficient to justify the high cost associated with regenerative medicine, definitive structural improvement that would last for years or decades and obviate or delay the need for joint arthroplasty is essential for regenerative medicine to retain a place among OA treatment methods. Cite this article:
This study aimed to investigate whether human umbilical cord mesenchymal stem cells (UC-MSCs) can prevent articular cartilage degradation and explore the underlying mechanisms in a rat osteoarthritis (OA) model induced by monosodium iodoacetate (MIA). Human UC-MSCs were characterized by their phenotype and multilineage differentiation potential. Two weeks after MIA induction in rats, human UC-MSCs were intra-articularly injected once a week for three weeks. The therapeutic effect of human UC-MSCs was evaluated by haematoxylin and eosin, toluidine blue, Safranin-O/Fast green staining, and Mankin scores. Markers of joint cartilage injury and pro- and anti-inflammatory markers were detected by immunohistochemistry.Aims
Methods
Ageing-related incompetence becomes a major hurdle for the clinical translation of adult stem cells in the treatment of osteoarthritis (OA). This study aims to investigate the effect of stepwise preconditioning on cellular behaviours in human mesenchymal stem cells (hMSCs) from ageing patients, and to verify their therapeutic effect in an OA animal model. Mesenchymal stem cells (MSCs) were isolated from ageing patients and preconditioned with chondrogenic differentiation medium, followed by normal growth medium. Cellular assays including Bromodeoxyuridine / 5-bromo-2'-deoxyuridine (BrdU), quantitative polymerase chain reaction (q-PCR), β-Gal, Rosette forming, and histological staining were compared in the manipulated human mesenchymal stem cells (hM-MSCs) and their controls. The anterior cruciate ligament transection (ACLT) rabbit models were locally injected with two millions, four millions, or eight millions of hM-MSCs or phosphate-buffered saline (PBS). Osteoarthritis Research Society International (OARSI) scoring was performed to measure the pathological changes in the affected joints after staining. Micro-CT analysis was conducted to determine the microstructural changes in subchondral bone.Aims
Methods
The hypothesis of this study was that bone peg fixation in the treatment of osteochondral lesions of the talus would show satisfactory clinical and radiological results, without complications. Between September 2014 and July 2017, 25 patients with symptomatic osteochondritis of the talus and an osteochondral fragment, who were treated using bone peg fixation, were analyzed retrospectively. All were available for complete follow-up at a mean 22 of months (12 to 35). There were 15 males and ten females with a mean age of 19.6 years (11 to 34). The clinical results were evaluated using a visual analogue scale (VAS) and the American Orthopaedic Foot and Ankle Society (AOFAS) score preoperatively and at the final follow-up. The radiological results were evaluated using classification described by Hepple et al based on the MRI findings, the location of the lesion, the size of the osteochondral fragment, and the postoperative healing of the lesion.Aims
Methods
This systematic review examines the current literature regarding surgical techniques for restoring articular cartilage in the hip, from the older microfracture techniques involving perforation to the subchondral bone, to adaptations of this technique using nanofractures and scaffolds. This review discusses the autologous and allograft transfer systems and the autologous matrix-induced chondrogenesis (AMIC) technique, as well as a summary of the previously discussed techniques, which could become common practice for restoring articular cartilage, thus reducing the need for total hip arthroplasty. Using the
Mesenchymal stem cells (MSCs) have several properties that may support their use as an early treatment option for osteoarthritis (OA). This study investigated the role of multiple injections of allogeneic bone marrow-derived stem cells (BMSCs) to alleviate the progression of osteoarthritic changes in the various structures of the mature rabbit knee in an anterior cruciate ligament (ACL)-deficient OA model. Two months after bilateral section of the ACL of Japanese white rabbits aged nine months or more, either phosphate buffered saline (PBS) or 1 x 106 MSCs were injected into the knee joint in single or three consecutive doses. After two months, the articular cartilage and meniscus were assessed macroscopically, histologically, and immunohistochemically using collagen I and II.Aim
Materials and Methods
The aim of this study was to report the outcome of femoral condylar fresh osteochondral allografts (FOCA) with concomitant realignment osteotomy with a focus on graft survivorship, complications, reoperation, and function. We identified 60 patients (16 women, 44 men) who underwent unipolar femoral condylar FOCA with concomitant realignment between 1972 and 2012. The mean age of the patients was 28.9 years (10 to 62) and the mean follow-up was 11.4 years (2 to 35). Failure was defined as conversion to total knee arthroplasty, revision allograft, or graft removal. Clinical outcome was evaluated using the modified Hospital for Special Surgery (mHSS) score.Aims
Patients and Methods
The aim of this study was to investigate the effect of granulocyte-colony stimulating factor (G-CSF) on mesenchymal stem cell (MSC) proliferation MSCs from rabbits were cultured in a control medium and medium with G-CSF (low-dose: 4 μg, high-dose: 40 μg). At one, three, and five days after culturing, cells were counted. Differential potential of cultured cells were examined by stimulating them with a osteogenic, adipogenic and chondrogenic medium. A total of 30 rabbits were divided into three groups. The low-dose group (n = 10) received 10 μg/kg of G-CSF daily, the high-dose group (n = 10) received 50 μg/kg daily by subcutaneous injection for three days prior to creating cartilage defects. The control group (n = 10) was administered saline for three days. At 48 hours after the first injection, a 5.2 mm diameter cylindrical osteochondral defect was created in the femoral trochlea. At four and 12 weeks post-operatively, repaired tissue was evaluated macroscopically and microscopically.Objectives
Methods
Human articular cartilage samples were retrieved from the resected material of patients undergoing total knee replacement. Samples underwent automated controlled freezing at various stages of preparation: as intact articular cartilage discs, as minced articular cartilage, and as chondrocytes immediately after enzymatic isolation from fresh articular cartilage. Cell viability was examined using a LIVE/DEAD assay which provided fluorescent staining. Isolated chondrocytes were then cultured and Alamar blue assay was used for estimation of cell proliferation at days zero, four, seven, 14, 21 and 28 after seeding. The mean percentage viabilities of chondrocytes isolated from group A (fresh, intact articular cartilage disc samples), group B (following cryopreservation and then thawing, after initial isolation from articular cartilage), group C (from minced cryopreserved articular cartilage samples), and group D (from cryopreserved intact articular cartilage disc samples) were 74.7% (95% confidence interval (CI) 73.1 to 76.3), 47.0% (95% CI 43 to 51), 32.0% (95% CI 30.3 to 33.7) and 23.3% (95% CI 22.1 to 24.5), respectively. Isolated chondrocytes from all groups were expanded by the following mean proportions after 28 days of culturing: group A ten times, group B 18 times, group C 106 times, and group D 154 times. This experiment demonstrated that it is possible to isolate viable chondrocytes from cryopreserved intact human articular cartilage which can then be successfully cultured.
Mesenchymal stem cells have the ability to differentiate into various cell types, and thus have emerged as promising alternatives to chondrocytes in cell-based cartilage repair methods. The aim of this experimental study was to investigate the effect of bone marrow derived mesenchymal stem cells combined with platelet rich fibrin on osteochondral defect repair and articular cartilage regeneration in a canine model. Osteochondral defects were created on the medial femoral condyles of 12 adult male mixed breed dogs. They were either treated with stem cells seeded on platelet rich fibrin or left empty. Macroscopic and histological evaluation of the repair tissue was conducted after four, 16 and 24 weeks using the International Cartilage Repair Society macroscopic and the O’Driscoll histological grading systems. Results were reported as mean and standard deviation (Objectives
Methods
Osteochondritis Dissecans (OCD) is a condition
for which the aetiology remains unknown. It affects subchondral bone
and secondarily its overlying cartilage and is mostly found in the
knee. It can occur in adults, but is generally identified when growth
remains, when it is referred to as juvenile OCD. As the condition
progresses, the affected subchondral bone separates from adjacent
healthy bone, and can lead to demarcation and separation of its associated
articular cartilage. Any symptoms which arise relate to the stage
of the disease. Early disease without separation of the lesion results
in pain. Separation of the lesion leads to mechanical symptoms and
swelling and, in advanced cases, the formation of loose bodies. Early identification of OCD is essential as untreated OCD can
lead to the premature degeneration of the joint, whereas appropriate
treatment can halt the disease process and lead to healing. Establishing
the stability of the lesion is a key part of providing the correct
treatment. Stable lesions, particularly in juvenile patients, have
greater propensity to heal with non-surgical treatment, whereas
unstable or displaced lesions usually require surgical management. This article discusses the aetiology, clinical presentation and
prognosis of OCD in the knee. It presents an algorithm for treatment,
which aims to promote healing of native hyaline cartilage and to
ensure joint congruity. Take home message: Although there is no clear consensus as to
the best treatment of OCD, every attempt should be made to retain
the osteochondral fragment when possible as, with a careful surgical
technique, there is potential for healing even in chronic lesions Cite this article:
The management of failed autologous chondrocyte
implantation (ACI) and matrix-assisted autologous chondrocyte implantation
(MACI) for the treatment of symptomatic osteochondral defects in
the knee represents a major challenge. Patients are young, active
and usually unsuitable for prosthetic replacement. This study reports
the results in patients who underwent revision cartilage transplantation
of their original ACI/MACI graft for clinical or graft-related failure.
We assessed 22 patients (12 men and 10 women) with a mean age of
37.4 years (18 to 48) at a mean of 5.4 years (1.3 to 10.9). The
mean period between primary and revision grafting was 46.1 months
(7 to 89). The mean defect size was 446.6 mm2 (150 to
875) and they were located on 11 medial and two lateral femoral condyles,
eight patellae and one trochlea. The mean modified Cincinnati knee score improved from 40.5 (16
to 77) pre-operatively to 64.9 (8 to 94) at their most recent review
(p <
0.001). The visual analogue pain score improved from 6.1
(3 to 9) to 4.7 (0 to 10) (p = 0.042). A total of 14 patients (63%)
reported an ‘excellent’ (n = 6) or ‘good’ (n = 8) clinical outcome,
5 ‘fair’ and one ‘poor’ outcome. Two patients underwent patellofemoral
joint replacement. This study demonstrates that revision cartilage
transplantation after primary ACI and MACI can yield acceptable
functional results and continue to preserve the joint. Cite this article:
The August 2015 Research Roundup360 looks at: Lightbulbs, bleeding and procedure durations; Infection and rheumatoid agents; Infection rates and ‘bundles of care’ revisited; ACI: new application for a proven technology?; Hydrogel coating given the thumbs up; Hydroxyapatite as a smart coating?
