Stem cells

We have been in stem cell research for over a decade now with A/Prof Suresh Nathan having published one of the earliest stem cell papers in Singapore. There is no evidence that stem cell therapy works in osteoarthritis. Injectable preparations of stem cells into arthitic knees have been claimed to provide benefit but this is very likely a placebo effect. One must consider again the pathology in the arthritic knee. In osteoarthritis there are changes to the cartilage which are worn away (loss of joint space) and then these die and become osteophytes. The bone is exposed and becomes hardened (subchondral sclerosis) and the joint loses it shock absorbance and become prone to cracks. The underliying bone to this bone loses its integrity and becomes weak (cysts). The anatomy becomes distorted and the ligaments become stretched (varus or valgus). These five changes higlighted in italics are considered the hallmarks of osteoarthritis.

Therefore for stem cells to be effective in the arthritic knee, the 5 factors that need to be addressed are

  1. Loss of joint space: The principal state that stem cell therapy hopes to reverse.

  2. Reversal of osteophytes: Only possible through surgical removal

  3. Subchondral sclerosis: Only possible through a procedure known as microfracture where the surface is broken allowing stem cells from inside the bone to repopulate the defect. This procedure itself is known to be as good as stem cell therapy in these cases.

  4. Cysts: Only possible through surgical filling with bone graft.

  5. Varus or valgus: Only possible through surgical bone realignment procedures.

By the time one considers so many variables in such a procedure, one is already looking at a 2 to 3 hour operation including further time spent for the harvesting of stem cells, growing in the lab and replantation. By contrast, it takes about 1 hour to do a knee replacement in a procedure that allows the patient to walk immediately.

The place of stem cell therapy in osteoarthritis is questionable by present understanding. It is not supported for use in the literature.

By stark contrast, however, stem cell therapy of one form or other is eminently suited to the isolated defect in the femoral condyle. This is not arthritis per se but a defect in the cartilage (Figure 1). Generally, an arthroscopic evaluation is required (Figure 2) which should determine if this is an isolated defect or part of a more generalized process in the knee (Figure 2). Of course an MRI may be done pre-operatively but this can sometimes be inaccurate as it cannot really distinguish between cartilage and a defect that has been filled over with scar tissue. In the past stem cell therapy used to be a multi-step process involving harvesting cartilage in one sitting through a scope, growing it in a lab and then re-implanting it again later. Nevertheless, this procedure has not been found to be superior to the microfracture technique (Figure 3). More recently this latter technique has been refined to incorporate a membrane to trap stem cells (Figure 4, video). As discussed before, if the knee is malaligned the defect needs to be off-loaded to allow the cartilage to grow (Figure 5).

We have published some of the earliest work in stem cell research in Singapore (Nathan S et al, Tissue Engineering 2003). There is no question that stem cell implantation will reconstitute a cartilage defect (Figure 6). By present technologies however we are unable to maintain cartilage integrity and it usually breaks down in the long term. The procedure is therefore thought of more as a temporizing measure (Figure 7). Nevertheless, for the acute needs of sporting activity the new cartilage that grows is known to function admirably (Figure 8).

Figure 1. Stem cell therapy is best suited to a knee that has no other abnormality than a defect that has resulted from trauma measuring about 2 cm squared. More recently the indications have been pushed to defects up to 4 cm squared or with arthritis but the results have been equivocal.

Figure 2. In a typical arthroscopic assessment it should be fairly certain if the defect is localized to either the patellofemoral (a), medial compartment (b) or lateral compartment (c). Stem cell therapy is eminently suited to small defects in the medial compartment (b).

Figure 3. In microfractures, the defect is punctured using a microfracture awl (a). This results in stem cells being liberated from the bone marrow onto the surface (b). More recently attempts have been made at containing these escaping stem cells using a membrane (c).

Figure 4. The procedure is demonstrated in a company distributed video (courtesy of Hyalofast).

Figure 5. Now that the defect is filled in, it needs to be off-loaded by re-distributing the forces at the knee (a). This can be done with an external brace (b) which can be cumbersome or an internal realignment procedure (c).

Figure 6. In pre-clinical trials in rabbits, stem cell therapy has been shown to readily reconstitute defects (Nathan S et al, 2003).

Figure 7. Unfortunately the results tend to be temporary and in human subjects it is believed more to be a stop gap measure than a definitive treatment like knee replacement surgery (Nathan S et al, 2003).

Figure 8. The mechanical performance of this stem cell implantation is known to be promising until it wears off (Nathan S et al, 2003).

Figure 9. Hyalofast procedure performed on a traumatic femoral condyle ulcer in an athlete who returned to sports a year later

Figure 10. Patella (Knee cap) cartilage ulcers are challenging to perform stem cell transplants on. We have now acquired the technology to perform the procedure in these difficult situations permitting patients to return to sporting activities like running.