Treating back pain with mesenchymal stem cells

Pittsburgh, Pennsylvania -

Vertebral disc degeneration is a major cause of suffering internationally.  Although various interventions exist, such as disc replacement and surgical fusion, these have numerous long-term limitations such as need for resurgery, degeneration of the adjacent disc, and relapse of pain.  One exciting method of treating disc degeneration involves the administration of stem cells into the nucleus pulposus in order to reverse the degenerative events.  Previous studies have demonstrated that this is possible in animal models.  For example, Sakai et al (Differentiation of mesenchymal stem cells transplanted to a rabbit degenerative disc model: potential and limitations for stem cell therapy in disc regeneration. Spine. 2005 Nov 1;30(21):2379-87)demonstrated that injection of bone marrow derived mesenchymal cells into the pulposus resulted in the differentiation of the cells into cells expressing markers of nucleus pulposus cells such as Type I and II collagen, aggrecan and versican.  Given that mesenchymal stem cells are already in clinical trials, and have been reported to possess a good safety profile, the translation of these cells into a practical, off the shelf, method of treating lumbar disc degeneration appears promising.

However one important question is how the mesenchymal stem cells can actually differentiate into cells of the nucleus pulposus? In a recent study (Vadala et al Coculture of bone marrow mesenchymal stem cells and nucleus pulposus cells modulate gene expression profile without cell fusion. Spine. 2008 Apr 15;33(8):870-6) this question was examined.

The investigators used a three dimensional culture system in which male bone marrow derived mesenchymal stem cells were cocultured with female nucleus pulposus cells.  The investigators found that 2 weeks after coculture:

- The mesenchymal stem cells developed a gene expression profile (assessed by microarray) that was consistent with a chondrogenic phenotype.

- There was little stimulation of the nucleus pulposus cells by the cultured bone marrow mesenchymal stem cells.

- Cell fusion between the nucleus pulposus cells and the bone marrow mesenchymal stem cells was not observed.

These data provide some mechanistic understanding for how the bone marrow derived mesenchymal stem cells may be used to regenerate cells that are important for the disc to maintain its proper shape.  One thing that the investigators did not look at, but would have been nice to, is to see whether epigenetic agents such as valproic acid could increase the rate of differentiation of the bone marrow mesenchymal stem cells into nucleus pulposus cells. 

One of the problems with stem cell research, whether it is embryonic or adult is that the actual in vivo importance of findings is sometimes difficult to ascertain from looking at highly defined in vitro experiments.  For example, it is unclear how similar the coculture differentiated mesenchymal stem cells actually resembled nucleus pulposus cells.  Would the differentiation be enough to actually regenerate the disc?  Even if the disc is regenerated with new nucleus pulposus cells, would that make the pain actually go away?

As an aside, it should be noted that issued patents do exist in this area.  For example, US patent # 6723335 actually contains claims such as "A fluid matrix for treating intervertebral disc disease in a vertebrate, said fluid comprising cross-linked, decellularized nucleus pulposus tissue of a donor vertebrate....with the fluid matrix of further comprising a growth factor....fluid matrix further comprising a plurality of living cells...plurality of living cells comprise chondrocytes other than the chondrocytes of the donor vertebrate...plurality of living cells comprise mesenchymal stem cells."

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