Autologous Chondrocyte Implantation A Systematic Review
ABSTRACT The purpose of the present study was to determine (1) whether the current literature supports the choice of using autologous chondrocyte implantation over other cartilage procedures with regard to clinical outcome, magnetic resonance imaging, arthroscopic assessment, and durability of treatment, (2) whether the current literature supports the use of a specific generation of autologous chondrocyte implantation, and (3) whether there are patient-specific and defect-specific factors that influence outcomes after autologous chondrocyte implantation in comparison with other cartilage repair or restoration procedures.
We conducted a systematic review of multiple databases in which we evaluated Level-I and II studies comparing autologous chondrocyte implantation with another cartilage repair or restoration technique as well as comparative intergenerational studies of autologous chondrocyte implantation. The methodological quality of studies was evaluated with use of Delphi list and modified Coleman methodology scores. Effect size analysis was performed for all outcome measures.
Thirteen studies (917 subjects) were included. Study methodological quality improved with later publication dates. The mean modified Coleman methodology score was 54 (of 100). Patients underwent autologous chondrocyte implantation (n = 604), microfracture (n = 271), or osteochondral autograft (n = 42). All surgical techniques demonstrated improvement in comparison with the preoperative status. Three of seven studies showed better clinical outcomes after autologous chondrocyte implantation in comparison with microfracture after one to three years of follow-up, whereas one study showed better outcomes two years after microfracture and three other studies showed no difference in these treatments after one to five years. Clinical outcomes after microfracture deteriorated after eighteen to twenty-four months (in three of seven studies). Autologous chondrocyte implantation and osteochondral autograft demonstrated equivalent short-term clinical outcomes, although there was more rapid improvement after osteochondral autograft (two studies). Although outcomes were equivalent between first and second-generation autologous chondrocyte implantation and between open and arthroscopic autologous chondrocyte implantation, complication rates were higher with open, periosteal-cover, first-generation autologous chondrocyte implantation (four studies). Younger patients with a shorter preoperative duration of symptoms and fewer prior surgical procedures had the best outcomes after both autologous chondrocyte implantation and microfracture. A defect size of >4 cm(2) was the only factor predictive of better outcomes when autologous chondrocyte implantation was compared with a non-autologous chondrocyte implantation surgical technique.
Cartilage repair or restoration in the knee provides short-term success with microfracture, autologous chondrocyte implantation, or osteochondral autograft. There are patient-specific and defect-specific factors that influence clinical outcomes.
- SourceAvailable from: Marcella Folin
[Show abstract] [Hide abstract]
- "In case of damage, cartilage is not capable of healing as it is an avascular and aneural tissue; moreover, its cellular components, chondrocytes, have low mitotic ability [3, 4]. Cartilage lesions are generally believed to progress to severe forms of osteoarthritis [5, 6], leading to pathologic changes in the joints with consequent pain, inflammation, and functional disability [7, 8]. Injuries which reach the subchondral bone may induce a systemic reaction and generate reparative tissue. "
ABSTRACT: Articular cartilage lesions are a particular challenge for regenerative medicine due to cartilage low self-ability repair in case of damage. Hence, a significant goal of musculoskeletal tissue engineering is the development of suitable structures in virtue of their matrix composition and biomechanical properties. The objective of our study was to design in vitro a supporting structure for autologous chondrocyte growth. We realized a biohybrid composite scaffold combining a novel and nonspecific extracellular matrix (ECM), which is decellularized Wharton's jelly ECM, with the biomechanical properties of the synthetic hydrogel polyvinyl alcohol (PVA). Wharton's jelly ECM was tested for its ability in promoting scaffold colonization by chondrocytes and compared with polyvinyl alcohol itself and the more specific decellularized cartilage matrix. Our preliminary evidences highlighted the chance of using Wharton's jelly ECM in combination with PVA hydrogels as an innovative and easily available scaffold for cartilage restoration.BioMed Research International 07/2014; 2014:762189. DOI:10.1155/2014/762189 · 3.17 Impact Factor
[Show abstract] [Hide abstract]
- "In osteoarthritis (OA), a relative increase in the production of these enzymes can result in aberrant cartilage destruction . Autologous chondrocyte implantation (ACI) of ex vivo expanded chondrocytes retaining ability to repopulate focal lesions of articular cartilage  is an important therapeutic aim in orthopaedics. When cultured in supporting 3D scaffold substitute structures, chondrocytes maintain the production of collagen type II, aggrecans, and MMP13, whereas in monolayer cultures they display a progressive loss of these characteristic proteins and eventually gain a fibroblast-like phenotype and switch to collagen type I expression instead of type II, that reflects a dedifferentiated status. "
ABSTRACT: Articular chondrocytes are responsible for the maintenance of healthy articulations; indeed, dysregulation of their functions, including the production of matrix proteins and matrix-remodeling proteases, may result in fraying of the tissue and development of osteoarthritis (OA). To explore transcriptional mechanisms that contribute to the regulation of chondrocyte homeostasis and may be implicated in OA development, we compared the gene expression profile of a set of zinc finger proteins potentially linked to the control of chondrocyte differentiation and/or functions (ZNF423, ZNF470, ZNF521, and ZNF780B) in chondrocytes from patients affected by OA and from subjects not affected by OA. This analysis highlighted a significantly lower expression of the transcript encoding ZNF423 in chondrocytes from OA, particularly in elderly patients. Interestingly, this decrease was mirrored by the similarly reduced expression of PPARγ, a known target of ZNF423 with anti-inflammatory and chondroprotective properties. The ZNF521 mRNA instead was abundant in all primary chondrocytes studied; the RNAi-mediated silencing of this gene significantly altered the COL2A/COL1 expression ratio, associated with the maintenance of the differentiated phenotype, in chondrocytes cultivated in alginate beads. These results suggest a role for ZNF423 and ZNF521 in the regulation of chondrocyte homeostasis and warrant further investigations to elucidate their mechanism of action.Mediators of Inflammation 05/2014; 2014:318793. DOI:10.1155/2014/318793 · 3.24 Impact Factor
[Show abstract] [Hide abstract]
- "Most of the RM interventions for orthopedics are still in the preclinical phase, although some early clinical (including first-in-human) studies have commenced and several have been completed       . Today only one orthopedic RM treatment, specifically the treatment for focal knee cartilage defects, is approved for market use  . As the amount of (early) clinical studies in this field is expected to rapidly expand in the near future, it is time to proactively discuss the scientific and ethical issues involved in the translation of preclinical research into clinical studies. "
ABSTRACT: Regenerative Medicine (RM) interventions, such as (stem) cell transplantation, scaffolds, gene transfer, and tissue engineering, are likely to change the field of orthopedics considerably. These strategies will significantly differ from treatments in current orthopedic practice, as they treat the underlying cause of disease and intervene at a biological level, preferably in an earlier stage. Whereas most of the RM interventions for orthopedics are still in the preclinical phase of research, the amount of clinical studies is expected to increase rapidly in the future. The debate about the challenging scientific and ethical issues of translating these innovative interventions into (early) clinical studies is developing. However, no empirical studies that have systematically described the attitudes, opinions, and experiences of experts in the field of orthopedic RM concerning these challenges exist. The aim of this study is to identify ethical issues which experts in the area of RM for musculoskeletal disorders consider to be relevant to address in order to properly translate RM interventions into (early) clinical studies. Study design/setting: In-depth qualitative interviews were conducted with 36 experts in the field, mainly spine surgeons and musculoskeletal scientists from the Netherlands and the United Kingdom(UK). A topic list of open questions, based on existing literature and pilot interviews, was used to guide the interviews. Data analysis was based on the constant comparative method, which means going back and forth from the data to develop codes, concepts and themes. Four ethical themes emerged from the interview data. First, the risks to study participants. Second, the appropriate selection of study participants. Third, setting relevant goal(s) for measuring outcome, varying from regenerating tissue to improving well-being of patients. Finally, the need for evidencebased medicine and scientific integrity, which is considered challenging in orthopedics. The overall attitude towards the development of RM was positive, especially since current surgical treatments for spine disorders lack satisfactory effectiveness. However, efforts should be taken to adequately address the ethical and scientific issues in the translation of RM interventions into clinical research. This is required to prevent unnecessary risks to study participants, to prevent exposure of future patients to useless clinical applications, as well as to prevent this young field from developing a negative reputation. Not only will the orthopedic RM field benefit from ethically and scientifically sound clinical studies, but the rise of RM also provides an opportunity to stimulate evidence-based practice in orthopedics and address hype- and profit driven practices in orthopedics.The spine journal: official journal of the North American Spine Society 10/2013; 14(6). DOI:10.1016/j.spinee.2013.10.016 · 2.43 Impact Factor