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June 11, 2010

Regenerative therapies using scaffolds

by Chris Kamel

When using stem cells for regenerative therapies, there are a few approaches that can be taken. Donor cells have issues with matching and immune rejection. Autologous stem cells transplants skirt rejection issues, but both strategies still face challenges associated with the ex vivo expansion of cells, such as culture consistency and the need for better protocols to monitor and reduce accumulated genetic changes. An alternative approach is to harness the body's endogenous stem cells to stimulate healing and regeneration. To this end, scientists at Columbia University have been experimenting with cell homing techniques rather than transplantation. The paper, published in the Journal of Dental Research, successfully uses these methods in an animal model for tooth regeneration.

In the study, rat incisors were extracted and replaced with an anatomically shaped scaffold to serve as a template for the new tooth. Rather than infusing with stem cells, the scaffold was loaded with two growth factors: stromal-derived factor-1 (SDF1) to attract native endothelial and bone marrow stem cells, and bone morphogenetic protein-7 (BMP7) to encourage proper differentiation, mineralization and blood vessel formation. Nine weeks later, the re-grown teeth were excised and were shown to have integrated well with surrounding tissue, something current implants don't do which can cause them to fail in a dynamic jaw environment. Unlike other transplants that use natural scaffolds - donor tissue stripped of cellular material - the tooth scaffold is made from a synthetic polymer. This is similar to work done by Dr. May Griffith of the Ottawa Hospital Research Institute and University of Ottawa Eye Institute who has developed an artificial cornea that supports growth of endogenous or transplanted cells and integration into the surrounding tissue. These implants are undergoing clinical trials in Sweden.

While dentists don't expect to see the dental technology in the clinic for at least five years, the natural growth process and relatively short recovery time (current implants can take several months for full recovery) make it an attractive solution to unattractive tooth loss. More importantly, it demonstrates proof-of-concept for using innate stem cell homing, rather than transplantation, for in situ tissue regeneration.

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