BOLAND CELL CHONDROCYTES
AUTOLOGOUS CHONDROCYTE IMPLANTATION FOR JOINT DAMAGE (ACI)
CLINICAL PROBLEM: knee cartilage damage in sportsmen
The clinical relevance and biological application of cultured, human , autologous chondrocytes is discussed. Severe traumatic defects in the articular cartilage of the knee in sportsmen may lead to troublesome osteoarthritis and eventual need for total knee replacement. Because of the poor capacity for cartilage repair and healing after cartilaginous injuries, ensuring satisfactory long- lasting treatment goals is a great challenge for orthopaedic surgeons and the patient. Current available treatments for damaged knee cartilage, such as microfracturing or mosaicplasty provide short- term, temporary relief after cartilage damage, but few ensure a long- lasting remedy.
BREAKTHROUGH IN CARTILAGE REPAIR
Now, Swedish researchers and orthopaedic surgeons describe a procedure in which cartilage from the same patient can be removed from a normal part of the injured knee, cultured in a laboratory, and implanted back at a later date into a deep traumatic cartilage defect in the same knee, to repair it through the formation of new cartilage. This means that your newly implanted cartilage cells grow and resurface the damaged defect in your knee. ACI appears to be a promising approach to repairing knee cartilage, particularly in young patients. Randomized, international studies show that ACI is as effective, but less invasive than microfracturing or mosaicplasty, both of which are also associated with morbidity. Up until now the procedure of cartilage cellular transplants, has been cost ineffective in South Africa. Research conducted by scientists in tissue engineering, and cellular culture at the University of Stellenbosch, in the Western Cape, has made autologous chondrocyte transplantation, and also referred to as ACI, now a reality. This treatment option for damaged knee cartilage, is now also, like in other areas in the world, available to state and private patients in South Africa, with significant traumatic chondral lesion, at substantially lower costs.
ORTHOPAEDIC SURGICAL TECHNIQUE OF ACI: HOW IT IS DONE
The orthopaedic intervention of ACI is performed, under general anaesthesia, in two stages, 4-6 weeks apart, by a multidisciplinary approach.
Step 1: after being selected and investigated with a knee cartilaginous injury, for this specialized treatment option, a biopsy of your knee cartilage is obtained, for laboratory culture purposes, during an arthroscopic examination of the same joint by your specialist orthopaedic surgeon. This requires general anaesthesia. A small cartilage sample is removed from a non-weight bearing area in the same affected joint and sent for cellular culturing in a tissue culture laboratory. This culturing technique and process takes 4-6 weeks, to regenerate sufficient chondrocytes and to expand your knee cartilage cells. The ultimate aim of ACI is to repair and resurface the knee cartilaginous defect with your own home grown cartilage, that has been cultured under aseptic techniques in an accredited cartilage laboratory.
Step 2: the cultured cells, also referred to as chondrocytes, after a period of expansion and stringent quality control and validation in the cartilage laboratory, are sent back (carefully packaged under aseptic conditions) to your orthopaedic surgeon after 4-6 weeks, for the definitive resurfacing of the cartilage defect in your knee joint. Usually the cells are embedded on a stabilizing scaffold explants or matrix, by tissue engineering, in the laboratory, that supports the cells. The second staged procedure of cartilage cellular implantation and defect resurfacing, involves the implantation of the autologous cultured cells into the cartilaginous defect after this lesion is cleaned and debrided. This debridement of the damaged cartilage provides a clean bed for the implantation of the new cells. Implantation of the cellular matrix may be via an open operation (arthrotomy) or arthroscopic approach depending on the operative choice or option recommended by your specialist. The cells and patch are glued, anchored or sutured to the cartilage defect, to avoid dislodgement, during the second stage of treatment. The second stage is also performed under general anaesthesia in an operating theatre. Thereafter a special orthopaedic rehabilitation program (for ACI) over months must be strictly adhered to (regards to knee exercises and weight bearing) and is essential to ensure a good and satisfactory result. Discuss this important aspect with your orthopaedic surgeon, beforehand. For success, you must be compliant and be prepared to follow your specialist’s recommendations. Regular follow up is needed, and in some cases, it is necessary to perform a further arthroscopy or MRI with cartilage sequencing, to assess the quality of the newly formed knee cartilage. Both these facilities are available in Cape Town. Many sportsmen with this disabling type of knee cartilage injury, has been able to return to competitive sport after a period of 12 months, having undergone ACI. You must give informed consent before ACI can be undertaken, because you have a chronic disabling condition affecting your knee and outcome, and this needs an informative, open and sensible, discussion with your specialist orthopaedic surgeon. This gives you the opportunity to discuss other options, current international results and recommendations, your aspirations, realistic expectations, prognosis, possible follow-up interventions and any downsides, or risks regarding ACI. Your excess cultured cells are not stored and are discarded.
PATIENT SELECTION FOR ACI
ACI means that you will resurface your knee cartilage with your own cells, and thereby has the great advantage, that you do not receive foreign cartilage or implants from another person, with the problems of rejection of transplantation. If you have severely damaged your knee cartilage during a fall, accident or sports incident, and have significant articular cartilage lesion, this may result in joint pain, swelling, catching and grinding. Candidates for treatment by autologous chondrocyte transplantation (ACI) are those sportsmen suffering clinically significant, symptomatic defects to the articular cartilage of the nee. Ask your orthopaedic surgeon if you qualify for cartilage resurfacing by ACI. ACI is generally applied to patients aged 15-55 years and is not recommended for generalized osteoarthritis or other forms of arthritis. The technology is now available in South Africa, and a tissue engineering chondrocyte laboratory is established in the Western Cape. Patient’s cartilage can be readily transported to the culture laboratory, for cellular regeneration and monolayer expansion in the new facility.
RESULTS OF ACI FOR DAMAGED KNEE ARTICULAR CARTILAGE
Dr. Lars Petersen, one of the Swedish pioneers of the cartilage cellular implantation technique with a personal 10-15 years experience, reports overall improvement in 83% of patients, if carefully selected. More than 10, 000 patients with severe knee cartilage damage, have undergone ACI in the western world and industrialized nations as of 2004. Patients with osteochondritis dissecans, a disabling condition that also affects the knees of young adults, also qualify for ACI, and gratifying results have been reported by some units. Data collection is ongoing to further document the long term patient experience, durability and efficacy of treatment (see NEJM 331: 889-895, Oct 6, 1994). Five patients have undergone ACI in South Africa.
HAVE PATIENTS WITH OTHER TRAUMATIC JOINT CARTILAGE DAMAGE BENEFITTED FROM ACI?
Yes, ACI has also been successfully applied in Europe and the United States in patients with traumatic chondral lesions affecting the hip- joint (acetabulum) and talus in the foot. ACI has also been used to repair damaged slipped and degenerated intervertebral discs in the back. In these cases, the orthopaedic procedure is considered to be investigational at the time of writing in 2006. Patients with knee cruciate ligaments sports injury, also at the same time of injury, may sustain troublesome accompanying cartilage damage. Your orthopaedic specialist will be able to advise you regards these options, and new developments in cartilage repair.
ASSOCIATED RISKS OF ACI
Precautions and warnings are issued by the manufacturer in the Directions for Use. Care is taken to ensure that the microbiological integrity of both the biopsy specimen and cultured chondrocytes is assured using aseptic practice. Cell viability is also tested. Joint infection after ACI is a rare complication. Joint infection is theoretical in a joint in persons undergoing arthroscopy or interventions, other than ACI. ACI is considered to be low risk orthopaedic procedure compared to joint replacement surgery. Failure rates after ACI may occur in 10-15% of such recipients, because the cells don’t work. In which case the patient is no worse off than before the cartilage transplant. In about 15% of patients undergoing ACI, it is necessary to do a second- look arthroscopy months after ACI, in order to assess the healing capacity of the newly grown cartilage and to deal with adhesions or overgrowth following the procedure. You must be prepared for this, because you have a chronic disabling, cartilaginous disorder affecting your knee joint, and is not considered a minor condition. Untreated traumatic cartilaginous injuries to the knee joint may progress to severe osteoarthritis with time and result in the need for joint replacement.
BOLAND CELL: SCIENTIFIC AND ACADEMIC DISCUSSION ( CHONDROCYTES)
Athletes and sportsmen ( women) who sustain a deep chondral lesion of the articular surface of the femoral condyles may with time develope traumatic joint osteoarthritis. Some, over decades may require artificial knee replacement. Chondral healing differs from skin healing in many respects. Large articular lesions ( exceeding 2 by 2 centimeters) heal predominantly by fibrocartilage. This is not as resilient as hyaline cartilage of the normal joint. With time the fibrocartilage may erode exposing the underlying bone. The apposing bone may also be exposed resulting in the articulation of bone on bone. This leads to severe pain , swelling and with time a joint effusion. Early treatment of traumatic deep chondral knee joint cartilage damage has been by bone drilling or mosaicplasty. Mosaicplasty means that small cores of harvested adjacent cartilage ( small cylinders) are autografted in the defect. Microfracturing means that tiny holes are drilled into the ulcerated surface. The latter procedure facilitates fibrocartilage deposition from the underlying bone. In controlled trials, autologous chondrocyte transplantation has faired no worse than microfracturing. It is an option that can be considered for knee joint cartilage regeneration and long term studies are in print that exceed 10 years. On both sides of the Atlantic, good results have been reported by enthusiastic researchers. Not all orthopaedic departments can offer this service because they have limited experience of biotechnology and joint cartilage regeneration by the biological route. Drawbacks have included graft failure and delamination. MRI is a good method to assess ACI results and to detect problems. Chondrocytes have been reported in investigational studies to be applicable for treatment of talar lesions and spinal disc degeneration in selected cases. It is still early days but cell therapy is where organ allograft transplantation was 20 years ago. Autologous chondrocyte transplantation was pioneered by Lars Petersen of Sweden. Other pioneers include Bentley of the UK, Brittberg and Midas. See resources: J Bone Joint Surg 2006:88, 503-7, J Bone Joint Surg 2006, 88:203-5.
FUTHER RESOURCES REGARDS ACI APPLICATION FOR PATIENTS
IS ACI COST EFFECTIVE TREATMENT AND WILL MY MEDICAL AID PAY?
The cost of ACI in Europe, Australia and the United States is prohibitive in excess of R80,000. Cartilage repair is Nappi-coded and most medical aids cover part of the costs of ACI in South Africa. The total average cost for cell culturing (about R5000) and scaffolds (R7000) is about R12,000. This fee excludes the hospital admission fee, theatre fee, theatre costs and the specialist fee.
CAN INTERVERTEBRAL DISCS BE REGENERATED BY THE USE OF CELLS?
Yes, but the procedure is investigational. A biopsy of the patients’ prolapsed disc is needed and the intervertabral disc chondrocytes can be cultivated. BOLAND CELL has specialized technologies in this field of spinal vertebral column regeneration.