A Visit from the Tooth Fairy: Adult Stem Cells from Baby Teeth Reveal Clues to Classic FOP

FOP is a challenging condition to study.
Since physical and surgical trauma exacerbates FOP by inducing

bone formation, it has been difficult to safely obtain biopsy

samples from FOP patients for detailed biochemical and

molecular analyses.


In a report published as the lead article in The Journal of

Bone and Mineral Research, we described adult stem cells

that were derived safely and non-traumatically from the

dental pulp of discarded primary teeth of FOP patients and

unaffected controls. These are the first FOP connective tissue

cells that have been used to study BMP signaling and bone

differentiation.

Drs. Shore and Kaplan meet with Dr. Petra
Seemann (far left) and Julia Haupt, doctoral
student (second from right), at the Mundlos-
Seemann Laboratory of the Max Planck Institute
for Molecular Genetics in Berlin, Germany.


The study showed that connective tissue stem cells from FOP

patients transmit increased BMP signals through both

developmental and inflammatory signaling pathways

downstream of the mutant receptor and respond to BMP

treatment by dramatically over-expressing BMP responsive

genes. FOP cells demonstrate leaky signaling at rest and

hyper-responsive signaling when stimulated by BMPs.
FOP cells also showed more rapid differentiation to bone

cells than normal control cells. Future studies with these cells

should substantially increase our understanding of FOP, providing

novel insights and screening tools for testing new therapies.


Mutant FOP Gene Enhances Cartilage
and Bone Formation

Heterotopic bone in FOP patients develops from an
intermediate cartilage stage. Recent studies in adult stem cells
indicate that the mutant FOP gene can in fact induce cartilage
as well as bone formation. Most importantly, these studies
make it possible to screen for drugs that will inhibit not only
bone formation but also the intermediary stage of cartilage
formation, and thus inhibit heterotopic ossification at an
earlier stage of development than might otherwise be possible.
The detailed results of these landmark studies will soon be
submitted for publication.