Proliferation and differentiation potential of chondrocytes from osteoarthritic patients

Autologous chondrocyte transplantation (ACT) has been shown, in long-term follow-up studies, to be a promising treatment for the repair of isolated cartilage lesions. The method is based on an implantation of in vitro expanded chondrocytes originating from a small cartilage biopsy harvested from a non-weight-bearing area within the joint. In patients with osteoarthritis (OA), there is a need for the resurfacing of large areas, which could potentially be made by using a scaffold in combination with culture-expanded cells. As a first step towards a cell-based therapy for OA, we therefore investigated the expansion and redifferentiation potential in vitro of chondrocytes isolated from patients undergoing total knee replacement. The results demonstrate that OA chondrocytes have a good proliferation potential and are able to redifferentiate in a three-dimensional pellet model. During the redifferentiation, the OA cells expressed increasing amounts of DNA and proteoglycans, and at day 14 the cells from all donors contained type II collagen-rich matrix. The accumulation of proteoglycans was in comparable amounts to those from ACT donors, whereas total collagen was significantly lower in all of the redifferentiated OA chondrocytes. When the OA chondrocytes were loaded into a scaffold based on hyaluronic acid, they bound to the scaffold and produced cartilage-specific matrix proteins. Thus, autologous chondrocytes are a potential source for the biological treatment of OA patients but the limited collagen synthesis of the OA chondrocytes needs to be further explained

WTC2005-63304 BIOTRIBOLOGY: THE WEAR RESISTANCE OF REPAIRED HUMAN ARTICULAR CARTILAGE

ABSTRACT Normal, mature articular cartilage does not spontaneously repair itself back to hyaline cartilage after an injury or degenerative disease (e.g., osteoarthritis)-problems of increasing importance in an aging population. A promising new approach is to repair damaged cartilage by a method known as Autologous Chondrocyte Implantation (ACI)-a technique pioneered and further developed by the Cartilage Research Unit at Goteborg University in Sweden. However, the tribological properties of the repaired cartilage, including the important property wear-resistance, are unknown. How durable is the repaired cartilage? How long will it last? One of the co-authors, Dr. Mats Brittberg, has provided 16 samples of 2mm diameter human biopsies from the knees of eight Swedish patients for testing in our biotribology device. This paper presents results of wear experiments on cartilage repaired by Brittberg's ACI technique and, for comparison, two other methods. Four of these samples (2 pairs) were from patients who had undergone the ACI procedure while another four were from those who had other methods of repair. A pair consists of a biopsy from the repaired area of the joint along with a sample from nearby "healthy" cartilage from the same joint. Thus, each pair allowed for a direct comparison of the tribological properties of the repaired cartilage to those of "normal" cartilage from the same joint. The results of this study show that the ACI method of cartilage repair gave substantially less wear than that of normal cartilage while spontaneous repair and abrasion arthroplasty produced higher wear. Friction levels were in the boundary lubrication regime and, in line with our previous experience, had no correlation with wear. Results obtained with cartilage from the remaining patients will be discussed in future papers

Cartilage Restoration and Allogeneic Chondrocyte Implantation: Innovative Technique

Articular cartilage lesions are frequent in young people with deleterious results if not treated properly. Various restorative techniques have been developed with the aim to overcome the limitations and short-term results of cartilage repair procedures. Cell therapy and tissue engineering techniques as Autologous Chondrocyte Implantation (ACI) have proved to induce cartilaginous tissue in joint defects with considerable long-term durability, currently being the gold standard in the treatment of medium to large cartilage injuries. Although results are encouraging and overall, the patients are satisfied, this technique is not exempt of limitations. These include the technical complexity and the costs of the two surgical procedures, de-differentiation of chondrocytes during in-vitro expansion and the limited amount of cartilage from a small biopsy. Here, we describe the recent advances in chondrocytes-based therapies for cartilage restoration, with a focus on the latest development in the use of allogeneic chondrocytes as a cell source. In allogeneic chondrocyte implantation, cells are harvested from cadaveric articular cartilage, and implanted in a scaffold into the cartilage defect. The advantages of this procedure are that there is no need for double surgeries, reduced patient morbidity and the availability of a large chondrocyte depot

Combined autologous chondrocyte implantation (ACI) with supra-condylar femoral varus osteotomy, following lateral growth-plate damage in an adolescent knee: 8-year follow-up

We report the 8-year clinical and radiographic outcome of an adolescent patient with a large osteochondral defect of the lateral femoral condyle, and ipsilateral genu valgum secondary to an epiphyseal injury, managed with autologous chondrocyte implantation (ACI) and supracondylar re-alignment femoral osteotomy. Long-term clinical success was achieved using this method, illustrating the effective use of re-alignment osteotomy in correcting mal-alignment of the knee, protecting the ACI graft site and providing the optimum environment for cartilage repair and regeneration. This is the first report of the combined use of ACI and femoral osteotomy for such a case

Injectable gellan gum hydrogels with autologous cells for the treatment of rabbit articular cartilage defects

In this work, the ability of gellan gum hydrogels coupled with autologous cells to regenerate rabbit full-thickness articular cartilage defects was tested. Five study groups were defined: (a) gellangumwith encapsulated chondrogenic predifferentiated rabbit adipose stem cells (ASCþGF); (b) gellan gum with encapsulated nonchondrogenic predifferentiated rabbit adipose stem cells (ASC); (c) gellan gum with encapsulated rabbit articular chondrocytes (AC) (standard control); (d) gellan gum alone (control); (e) empty defect (control). Fullthickness articular cartilage defects were created and the gellangum constructs were injected and left for 8 weeks. The macroscopic aspect of the explants showed a progressive increase of similarity with the lateral native cartilage, stable integration at the defect site, more pronouncedly in the cell-loaded constructs. Tissue scoring showed that ASCþGF exhibited the best results regarding tissue quality progression. Alcian blue retrieved similar results with a better outcome for the cell-loaded constructs. Regarding real-time PCR analyses, ASCþGF had the best progression with an upregulation of collagen type II and aggrecan, and a downregulation of collagen type I. Gellan gum hydrogels combined with autologous cells constitute a promising approach for the treatment of articular cartilage defects, and adipose derived cellsmayconstitute a valid alternative to currently used articular chondrocytes.J. T. Oliveira acknowledge the Portuguese Foundation for Science and Technology (FCT) for his grant (SFRH/BD17135/2004). The authors thank the medical and technical staff of the Institute for Biomedical Sciences Abel Salazar (ICBAS) of the University of Porto, Portugal and the Institute for Health and Life Sciences (ICVS) of the University of Minho, Portugal. The authors also thank Dr. Patricia Malafaya, Cristina Correia, and Rui Pereira, for their help with the histological scoring. This work was carried out under the scope of the European NoE EXPERTISSUES, and partially supported by the European Project HIPPOCRATES

Cell-based Approaches to Joint Surface Repair : A Research Perspective

The authors are grateful for support to their research from Arthritis Research UK (grants 19271, 19429, 19667, 20050). None of the authors received any funding related to the writing of this manuscript, and the funding bodies did not play any role in the writing of the manuscript or decision to submit the manuscript for publication.Peer reviewedPublisher PD

A multilayer biomaterial for osteochondral regeneration shows superiority vs microfractures for the treatment of osteochondral lesions in a multicentre randomized trial at 2 years

Purpose: The increasing awareness on the role of subchondral bone in the etiopathology of articular surface lesions led to the development of osteochondral scaffolds. While safety and promising results have been suggested, there are no trials proving the real potential of the osteochondral regenerative approach. Aim was to assess the benefit provided by a nanostructured collagen-hydroxyapatite (coll-HA) multilayer scaffold for the treatment of chondral and osteochondral knee lesions. Methods: In this multicentre randomized controlled clinical trial, 100 patients affected by symptomatic chondral and osteochondral lesions were treated and evaluated for up to 2 years (51 study group and 49 control group). A biomimetic coll-HA scaffold was studied, and bone marrow stimulation (BMS) was used as reference intervention. Primary efficacy measurement was IKDC subjective score at 2 years. Secondary efficacy measurements were: KOOS, IKDC Knee Examination Form, Tegner and VAS Pain scores evaluated at 6, 12 and 24 months. Tissue regeneration was evaluated with MRI MOCART scoring system at 6, 12 and 24 months. An external independent agency was involved to ensure data correctness and objectiveness. Results: A statistically significant improvement of all clinical scores was obtained from basal evaluation to 2-year follow-up in both groups, although no overall statistically significant differences were detected between the two treatments. Conversely, the subgroup of patients affected by deep osteochondral lesions (i.e. Outerbridge grade IV and OCD) showed a statistically significant better IKDC subjective outcome (+12.4 points, p = 0.036) in the coll-HA group. Statistically significant better results were also found for another challenging group: sport active patients (+16.0, p = 0.027). Severe adverse events related to treatment were documented only in three patients in the coll-HA group and in one in the BMS group. The MOCART score showed no statistical difference between the two groups. Conclusions: This study highlighted the safety and potential of a biomimetic implant. While no statistically significant differences were found compared to BMS for chondral lesions, this procedure can be considered a suitable option for the treatment of osteochondral lesions