orthopaedic specialist<\/a> from Louisiana.<\/p>\nDr Broyles was attracted to Malaysia by the results of a Malaysian clinical study on a technique that appears to improve on existing procedures.<\/p>\n
The study was led by Dr Saw, who has shown, together with researchers from Universiti Putra Malaysia (UPM), that they could regenerate normal cartilage in patients\u2019 knees by injecting the patient\u2019s own blood stem cells into their knees after drilling holes into the underlying bone.<\/p>\n
Dr Broyles was here to learn the technique.<\/p>\n
From goats to humans<\/h2>\n
Before trying the procedure (called Articular Cartilage Regeneration with Autologous Peripheral Blood Progenitor Cells and Hyaluronic Acid after Arthroscopic Subchondral Drilling, or ACR in short) in humans, Dr Saw and researchers from UPM tried to regenerate cartilage in the knee joints of goats in 2005.<\/p>\n
They harvested stem cells (bone marrow progenitor cells or BPMC) from goat bone marrow and injected them into the goats\u2019 knees, together with hyaluronic acid (a compound needed to build cartilage), after drilling holes in the cartilage and bones of their knee joints.<\/p>\n
After observing and documenting evidence of good cartilage repair in goats, Dr Saw and his team then proceeded to perform a pilot study on 10 patients. However, instead of using BMPC, Dr Saw tried using stem cells harvested from his patients\u2019 own blood (peripheral blood progenitor cells or PBPC), as it is safer and easier to harvest.<\/p>\n
\u201cRecent study into the properties of these PBPCs has shown that they are similar to embryonal stem cells in that they express transcription factors specific to pluripotential cells, have proliferative potential, have the ability to differentiate into a multitude of cell types, and are more immature than BPMCs,\u201d wrote Dr Saw and his team in a paper on the pilot study, published in the Arthroscopy Journal of Arthrosopic and Related Surgery early this month.<\/p>\n
The paper published the biopsy results of five of the patients who participated in the pilot study. \u201cAll of our biopsy specimens showed histologic features of hyaline cartilage …\u201d the researchers wrote.<\/p>\n
For those with very bad knees, knee replacement surgery may be the only option.
\nOne of the first patients who participated in the pilot study is 38-year-old Joanna Hart, an expatriate who was told she needed a knee replacement four years ago.<\/p>\n
The cartilage that prevented the bones in her left knee from rubbing against each other had worn off due to a less than satisfactory surgery she had to set her recurrently dislocated kneecap in place. As a result, she couldn\u2019t fully straighten her legs.<\/p>\n
As she was not keen on having her knees replaced, Hart decided to try the new procedure \u2013 then in its final stages of research in goats. \u201cMy knee has gradually improved over the last four years, and I had a second surgery two years ago to complete the stem cell therapy,\u201d she told Fit4Life in a recent email. (Both surgeries targeted different areas of her knee joints.)<\/p>\n
Two years after her first surgery, she was able to climb up the stairs to Batu Caves. Now, back in Scotland, she does five to eight gym classes a week, goes horse riding, and does a lot of walking. \u201cI can run without pain now too, but I don\u2019t do very much of that,\u201d she added.<\/p>\n
\u201cA majority of patients show progressive improvements, even up to three to four years, as opposed to the microfracture technique. International Knee Documentation Committee (IKDC) results ( scores used to chart patients\u2019 progress and long term results) following microfracture tend to deteriorate after two years,\u201d said Dr Saw.<\/p>\n
Nevertheless, in his experience, two patients had had bad falls onto their operated knees one year after surgery, and their knee function deteriorated. \u201cAnother middle-aged patient with a previous infected knee, who had underwent multiple surgeries, had a recurrence of bone spur and the patient chose to have a total knee replacement,\u201d he noted.<\/p>\n
Inducing repair, slowly<\/h2>\n
The steps involved in ACR may be simple, but the process of recovery is one that is long and time consuming.<\/p>\n
\u201cIt normally takes one or two years before patients can return to their normal sporting activities,\u201d explained Dr Saw.<\/p>\n
Before suggesting the procedure, orthopaedic surgeons have to assess their patients to determine if they need surgery to rectify their problem. \u201cThere are patients who only need physiotherapy or hyaluronic acid injections,\u201d he noted.<\/p>\n
Other treatment options include going on therapy or medication to help reduce the pain and discomfort, using supportive devices such as knee braces and orthoses to ease the stress or pressure on the joint.<\/p>\n
However, for those whose injuries are severe enough to warrant cartilage regeneration or replacement surgery, they have the options of going for a knee replacement surgery or cell-based regeneration therapies like the ACR and autologous chondrocyte implantation (ACI).<\/p>\n
In an ACI procedure, a patient\u2019s cartilage cells is harvested from the knee joint, multiplied in a lab, and re-implanted into the affected knee.<\/p>\n
\u201cIf their knees are bad enough to require a total knee replacement, there is no point in doing ACR. But there are a lot of patients who do not need a total knee replacement, and this is especially so for people who are in their 30\u2019s or 40\u2019s,\u201d said Dr Saw.<\/p>\n
First, a patient will have to undergo a minimally invasive \u201ckeyhole\u201d surgery to enable the surgeon to drill holes into the bones in their knees. One week after the surgery, the stem cells (PBPCs) in his blood will be harvested and injected (together with hyaluronic acid) into his knee.<\/p>\n
For the following four to five weeks, the patient will be given physiotherapy for two hours daily, and weekly stem cell and hyaluronic acid injections. (see How do doctors regenerate your cartilage with stem cells)<\/p>\n
\u201cThe risks are generally the same as any other minimally invasive procedures,\u201d said Dr Saw.<\/p>\n
Still, according to a patient information sheet distributed to participants of an ongoing randomised controlled trial, problems do occasionally occur, and there is a risk of infections, unsuccessful surgery, or less than satisfactory recovery.<\/p>\n
Although minor complications (like transient pain after surgery, the \u201clocking\u201d of the knee joint, and swelling that resolves within three to six months of surgery) are common, major complications like recurrent effusions (accumulation of fluid in the joint), infections, and blood clots are rare.<\/p>\n
Nevertheless, if the surgery is unsatisfactory, it is usually still possible for patients to undergo other types of cartilage repair surgery.<\/p>\n
Even so, Dr Saw said that there were no cases of infections or significant adverse events in the 50 patients recruited for the trial.<\/p>\n
Looking forward, working backwards<\/h2>\n
While Dr Saw and his co-authors acknowledged in their latest paper that the sample size (five patients) was too small and there were no control group to compare their results, Dr Saw is convinced that it works.<\/p>\n
But even though he thinks that ACR has great potential, he also acknowledged that it is only one of the several treatment approaches for managing cartilage injuries in joints \u2013 another tool in the bag.<\/p>\n
\u201cRight now, based on our studies, we know that it works,\u201d he said. But Dr Saw and his team want to know why and how ACR works, and how it compares to existing procedures. So, the next step for them is to understand the science behind the procedure by doing animal studies.<\/p>\n
\u201cWe are in the midst of completing a randomised clinical trial and writing a book chapter on cartilage regeneration,\u201d Dr Saw revealed.<\/p>\n
On top of that, he is also working with other doctors and equipment suppliers to design specific instruments for the procedure, as they are still using modified instruments.<\/p>\n
\u201cNow, we are basically in the process of improving the technique,\u201d he said.<\/p>\n
Even with international interest \u2013 surgeons from the US and countries in the region have visited Malaysia to learn about the procedure \u2013 ACR has yet to be performed in other countries due to regulatory requirements.<\/p>\n
\u201cWe are collaborating with Prof Gary Poehling at Wake Forrest University and Dr David McGuire from Anchorage, Alaska, in the set up of a multi-centre trial,\u201d said Dr Saw.<\/p>\n
Currently, we are collecting safety data from our patients in Kuala Lumpur for Wake Forrest University to present to the US FDA, he explained.<\/p>\n\t\t