[Emerging Spine Surgery Technologies] Safety and Complications Reporting on the Re-implantation of Culture-Expanded Mesenchymal Stem Cells using Autologous Platelet Lysate Technique

[Justin]

Below is from the Regenexx (Adult Stem Cell Therapy for Degenerative Disc Disease) thread and is posted here in the Education, Research and Spine Publications Forum for completeness.

Dear all,

This is Dr. Centeno, the developer of the Regenexx Disc procedure. I was asked by a colleague to respond to these posts, as this is a complex area and it helps to make sure everyone is informed. The cancer risk currently in the news about stem cells, mainly concerns embryonic stem cells. These are stem cells built to make a whole person, so they do have known tumor risks. Adult mesenchymal stem cells (they type used in the Regenexx procedure) are built to repair things in your body, so they have no significant cancer risks in animal studies when they are cultured for minimal periods (as in the Regenexx Disc procedure). We just published the world's largest complications and safety study in stem cell therapy to date (see below).

In this 3 year tracking period, we saw no evidence of cancer being caused by the cells. This doesn't absolutely rule out the risk of that something like this could occur, but if you look at the risks of low back surgery (fusion and/or laminectomy) and stack them up against our group of 227 patients, the risks of surgery would far outweigh any that were seen in our orthopedic applications. As an example, the serious complications rate for low back surgery is usually quoted in the 3-5% range, with some authors reporting complication rates as high as 40% for pedicle screw fusion. Applying those numbers to the 227 patients in this paper, would mean at a minimum of 7-12 patients with serious complications if the same group underwent low back surgery. This is much greater than the complication rates for orthopedic stem cell treatment delivered through a needle.

As far as the durability of the Regenexx disc procedure in patients that have responded, the long term outcomes are unknown. The oldest patients have only been tracked for the last 3-4 years. The major problem with all surgical disc approaches (nucleoplasty, laser spine surgery, discectomy, micro-discectomy, etc...) is that, in our opinion, removing tissue from the disc leads to more degenerative disc disease in the long run. If you use a bicycle tire analogy, our current state of the art is like trying to fix a bicycle tire failure with sandpaper. As an example, if you have a bike tire where the outer rubber casing is partially broken (in this case the outer annulus of the disc), the inner tube (in this case the nucleus pulposis or soft gel part of the inner disc) can cause the tire to have a bulge. We now fix that bulge by sanding down the outer rubber casing of the tire (removing pieces of the annulus) and thus weakening the structure. In the short run the bike will ride better, but the tire is now set up for structural failure down the road. We believe the Regenexx approach is akin to placing some glue in the tears and thus fixing the structure by healing the outer part of the disc. So in our opinion, cutting out pieces of this disc (no matter how carefully or minimally invasive), will eventually be replaced by a disc repair methodology.

Hope this helps!

Chris Centeno, M.D.

Curr Stem Cell Res Ther. 2009 Dec 2. [Epub ahead of print]

Safety and Complications Reporting on the Re-implantation of Culture-Expanded Mesenchymal Stem Cells using Autologous Platelet Lysate Technique.

Centeno CJ, Schultz JR, Cheever M, Robinson B, Freeman M, Marasco W.
Centeno-Schultz Clinic, Vail, Colorado, USA. PMID: 19951252

Mesenchymal stem cells (MSCs) hold great promise as therapeutic agents in regenerative medicine. Numerous animal studies have documented the multipotency of MSCs, showing their capabilities for differentiating into orthopedic tissues such as muscle, bone, cartilage, and tendon. However, the complication rate for autologous MSC therapy is only now beginning to be reported. Methods: Between 2005 and 2009, two groups of patients were treated for various orthopedic conditions with culture-expanded, autologous, bone marrow-derived MSCs (group 1: n=45; group 2: n=182). Cells were cultured in monolayer culture flasks using an autologous platelet lysate technique and re-injected into peripheral joints (n=213) or into intervertebral discs (n=13) with use of c-arm fluoroscopy. While both groups had prospective surveillance for complications, Group 1 additionally underwent 3.0T MRI tracking of the re-implant sites.

Results: Mean follow-up from the time of the re-implant procedure was 10.6 +/- 7.3 months. Serial MRI's at 3 months, 6 months, 1 year and 2 years failed to demonstrate any tumor formation at the re-implant sites. Formal disease surveillance for adverse events based on HHS criteria documented 7 cases of probable procedure-related complications (thought to be associated with the re-implant procedure itself) and three cases of possible stem cell complications, all of which were either self-limited or were remedied with simple therapeutic measures. One patient was diagnosed with cancer; however, this was almost certainly unrelated to the MSC therapy.

Conclusions: Using both high field MRI tracking and general surveillance in 227 patients, no neoplastic complications were detected at any stem cell re-implantation site. These findings are consistent with other reports that also show no evidence of malignant transformation in vivo, following implantation of MSCs that were expanded in vitro for limited periods.

[sportsnut3007]

This is of course exciting stuff!!! I personally think the fda should help " monitor" this work but let him continue his research. Personally for procedures that are medical needs, I think the fda should do a year research on new things, after of course other researches have tested it on animals and in the lab, and then have 2 types of approval one approval after the year is experimental approval for all who want it, and another set of approval i guess 3-4 years later with full fda stamping. Also, is it just me or do I see a future in which all get their discs regenerated every few years or however long the regeneration lasts by stemcells?