Update on stem cells for osteoarthritis…

Osteoarthritis affects nearly 27 million people in the United States, where it accounts for 25% of visits to primary care physicians, and 50% of all non-steroidal anti-inflammatory drug prescriptions. A significant percentage of patients with osteoarthritis go on to have joint replacement surgery.

Cartilage cannot heal itself. When damaged by injury or osteoarthritis, the effects can be long-lasting and permanent.

I’ve mentioned the work on nanofibers and stem cells being done at both the University of Pittsburgh and Northwestern University in previous posts.

Another approach is the actual growing of cartilage from stem cells in a laboratory.  This technique may one day repair damaged joints, according to research from the University of California, Davis, Department of Biomedical Engineering.

Dr. Kyriacos Athanasiou and his team have used adult stem cells from bone marrow and skin as well as human embryonic stem cells to grow cartilage tissue in the lab. Now they are experimenting with various chemical and mechanical stimuli to improve their initial results.

Work that Athanasiou’s group began in the early 1990’s at Rice University has resulted in the only FDA-approved products for treatment of small lesions on knee cartilage.

Athanasiou claims, “This will be live, biological cartilage that will not only fill defects, but will potentially be able to resurface the entire surface of joints that have been destroyed by osteoarthritis.”

Author’s note: I am so excited when I see stem cell research results for osteoarthritis!  While our efforts are promising, I want to reiterate, it is not effective for everyone.  We have had our share of non-responders. But we are learning more about patient selection criteria as well as making adjustments to joint mechanics following the procedure.

An article in Healthday (http://healthday.com/Article.asp?AID=635611) describes a new nanofiber gel that promotes cartilage growth in joints.

I had mentioned this in a previous post but this article succinctly outlines the implications.

In brief, the nanofiber material prompts stem cells in bone marrow to produce cartilage containing type II collagen and repair the damaged joint.

This is distinct from the Type I collagen produced by microfracture surgery. Type I collagen is not nearly as strong as Type II collagen.

I think if we could combine the autologous stem cell procedure we use right now and substitute the nanofiber material for the fat matrix we currently use, it might be better… but on the other hand, it may not be.  It’s definitely worth studying and comparing.  The advantages of fat are that it  is autologous and it also contains stem cells.

A news release issued by the American College of Rheumatology and authored by a friend and colleague, John Tesser, a rheumatologist in Phoenix, discusses Actemra for rheumatoid arthritis.

Here are some excerpts…

“Actemra (Tocilizumab)  is the first biologic agent specifically targeting IL-6.

It has demonstrated clinical efficacy in a number of RA populations. In the USA, it is currently approved only for tumor necrosis factor inhibitor failures. (Patients who’ve failed drugs like Enbrel, Humira, Remicade, Cimzia, and Simponi).

It is given once every 4 weeks as a 60 minute single intravenous drip infusion. The recommended starting dose when used as a single drug or in combination with disease modifying drugs, including methotrexate is 4 mg/kg, with the possibilityof increasing the dose to 8 mg/kg based on clinical response.

There is no set time duration needed prior to advancing to the 8 mg/kg dose and no other specific guidance as to what the clinical response should be. There is no data on intermediate doses between 4 and 8 mg/kg and no guidance on adjusting the dose for lean body weight; there is no dose adjustment for mild kidney impairment.

Tocilizumab has not been studied in patients with kidney failure or liver issues. A dose reduction from 8 to 4mg/kg is recommended in response to liver enzyme elevations,drop in white blood cell count, and/or drop in platelet count. Doses exceeding 800 mg per infusion are not recommended.

The cost of tocilizumab is estimated to be $1,060 to $2,125 per month, depending on the dose.

It has a safety profile similar to other biologic agents with respect to infections, including serious infections – i.e., a slight increased risk, including opportunistic infections. Other safety issues include low neutrophils (a type of white blood cell), low platelets, liver enzyme elevations, and lipid elevations, all of which need to be monitored according to guidance provided in the package insert.”

My take is that it is a good addition to our therapeutic arsenal for RA.  Not every patient responds to TNF inhibitors and this drug may serve as an “inbetween” before moving on to a drug like Rituxan.

Man oh man…

Not a day goes by when I’m asked by other docs… and regular folks too that question.  Calls from all over.  My response is to mention this recent report…

“In a review for F1000 Medicine Reports, Yves Henrotin and Jean-Emile Dubuc examined the range of therapies currently on offer for repairing cartilaginous tissue. They also considered how recent technological developments could affect the treatment of OA in elderly populations.

The most promising therapeutic technique, according to the authors,  is Autologous Chondrocyte Implantation (ACI), which involves non-invasively removing a small sample of cartilage from a healthy site, isolating and culturing cells, then re-implanting them into the damaged area.

A recent enhancement to this method is matrix-assisted ACI (MACI) – where the cultured cells are fixed within a biomaterial before being implanted to promote a smooth integration with the existing tissues. ACI and MACI have previously been reserved for younger patients who are not severely obese (i.e. with a BMI below 35), whose cartilage defect is relatively small and where other therapies have already been tried…”

And I mention this study to illustrate this fact…

I don’t agree with it at all!

For one thing, a recent report from Northwestern University has demonstrated…”nanoscopic fibers stimulate stem cells present in bone marrow to produce cartilage containing type II collagen and repair the damaged joint…”

This finding confirms previous reports from the University of Pittsburg. The future will be stem cells plus nanofibers used as a scaffold.

But, it should be mentioned that nanofiber technology is not being evaluated in people yet.  Still, it’s pretty clear that autologous (a patient’s own) stem cells will do a pretty decent job, depending on patient selection, technical approach, etc. And that autologous fat is a pretty good scaffold material.

My personal feeling is that in the future nanofibers will definitely help. How much better it will be than autologus fat, though, needs to be studied.

Stay tuned.

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