Laser-Activation of Dental Stem Cells Spurs Dentine Regeneration

A variety of experiments, clinical trials, and strategies have attempted to exploit stem cells as therapeutic agents in regenerative medicine. However, once stem cells are removed from their niches within the body and grown in artificial culture systems their properties can change. Such culture-acquired changes can often compromise the therapeutic potential of some stem cells. For this reason, the development of relatively simple but effective stem cell isolation and manipulation techniques represents someone of the prominent technical hurdles to the clinical use of stem cells.

Several laboratories have used exogenous factors to direct the differentiation of tissue-resident stem cells, but these exogenous factors can often cause unwanted side effects. For this reason, simpler manipulation techniques are always a welcome addition to the armamentarium of stem cell scientists.

To that end, Ashok B. Kulkarni from the National Institute of Dental and Craniofacial Research in Bethesda, MD and David J. Mooney from the Harvard School of Engineering and their colleagues and co-workers have used non-ionizing, low-power laser (LPL) treatments to activate host stem cells and promote tissue regeneration. This is a minimally invasive treatment that directs stem cells already present in tissues to heal damaged tissues.

LPL treatment was used to activate human dental stem cells in a laboratory culture system. Upon LPL treatment, the dental stem cells began to synthesize a powerful growth factor called transforming growth factor–β1 (TGF-β1). The endogenous synthesis of TGF-β1 and its receptor drove the dental stem cells to form dentin tubes.

When Kulkami and Mooney used an assay in animals called a “pulp capping model,” they discovered that LPL-activated dental stem cells were able to regenerate dentin after laser activation. To further demonstrate that these regenerative effects were the result of TGF-β1, Kalkami and Mooney and others made cells that did not have a functional TGF-β receptor II. This mutation completely abrogated the effects of LPL treatments. Also, if the dental stem cells were incubated with a TGF-βRI inhibitor, the effects of LPL on the dental stem cells was attenuated.

Thus, there is a simple and non-invasive way to activate a resident stem cell population in our bodies. Furthermore, the mechanisms by which LPL activates these stem cells has been defined as TGF-β mediated. These experiments also outlines the mechanism by which resident stem cells might be harnessed by means of light-activated endogenous cues for clinical regenerative applications. Exciting, huh?

STAP Author Agrees to Retract Both Nature Papers

STAP cells or Stimulus-Triggered Acquisition of Pluripotency cells were allegedly derived from adult mouse cells by subjecting those adult cells to a variety of environmental stresses. Even though the derivation of STAP cells was not terribly efficient, the ability to make pluripotent stem cells without viruses or the introduction of new genes seemed to be a godsend for stem cell scientists. Unfortunately, further testing and inquiries into STAP cells has revealed multiple problems and several labs have been completely unable to recapitulate the results of the researchers who reported the derivation of STAP cells. These problems have led many scientists to question the factuality of STAP cell derivation.

STAP cells took another hit this week when genetic tests of STAP cells indicated that those cells do not match the mice from which they were allegedly derived, according to a report from Nature News Blog.

The derivation of STAP cells were initially reported by Haruko Obokata from the RIKEN center and her colleagues. Given the remarkable nature of the claims in those papers, many scientists were skeptical and moved to test the protocols utilized by Obokata and others in those paper to make STAP cells from adult mouse cells. Unfortunately, these independent tests universally flopped, and an internal investigation by the Riken Center came to the conclusion that Dr. Obokata was guilty of research misconduct, which she has denied.

Teruhiko Wakayama, a scientist from Yamanashi University and one of the co-authors on the STAP papers, subjected some of the cell lines that he derived using the STAP approach back in March to a battery of genetic tests. He was dismayed to discover that some of these cell lines did not match the adult mice from which they were supposed to have been generated. This raises the possibility that the STAP cells are the result of contamination, which is a perennial problem in cell culture laboratories. Wakayama did not observe any anomalies with the lines reported in the Nature papers, but, just to be safe, he sent those and other lines to an independent, and unnamed, lab for further examination and corroboration.

These independent tests, according to reports from Japanese media sources, have found that none of the STAP cell lines match the mouse strains they were supposed to be from. This calls “into question whether the STAP phenomenon has ever been demonstrated.”

Last week, the Nature News Blog reported that Dr. Obokata had agreed to retract one of the two STAP papers, even though the retraction has yet to appear in print. Now, according to the ScienceInsider, Obokata has consented to retracting both Nature papers. The ScienceInsider added this will not end the STAP story, since Riken is doggedly trying to determine whether the STAP phenomenon exists and as some critics are asking how these flawed papers were published in the first place.

“The science of the two papers was rigorously, robustly peer-reviewed as part of our usual editorial procedures. Any inaccuracies in the presentation of data that may have come to light since the peer review are being investigated,” a spokesperson from Nature told ScienceInsider.