Eyeworld

EW NEWS & OPINION 34 September 2015 by Matt Young and Gloria D. Gamat EyeWorld Contributing Writers up with each new finding. "Ideally, we are hoping that in the future, patients who need to be treated for corneal scarring can use stem cells isolated from their own teeth," Dr. Syed-Picard said. While it is already known that there is variability in stem cell abundance among different patients, according to Dr. Syed-Picard, experts are not sure whether this will be a viable option for everyone. More research needs to be done to be able to understand patient variability, she said. Regenerative therapies beyond ophthalmology Human dental pulp contains a population of neural crest-derived, mesenchymal stem cells with the potential to differentiate into several cell types. Thus, experts believe that DPSCs can be used in regenerative therapies for other tissues and or- gans as well. Italian researchers reported in 2008 in Stem Cell Reviews and Reports that they have found dental pulp stem cells to be a promising tool for bone regeneration. Reporting in Medical Hypotheses in March 2015, Spanish researchers found the po- tential of dental pulp stem cells in generating a bioengineered human skin substitute for future clinical treatment. Japanese researchers reported in Cell Transplantation in April 2015 the potential of human dental pulp stem cells in peripheral nerve regeneration, thereby promot- ing angiogenesis. "There are several research groups that are studying dental pulp stem cells around the world," Dr. Syed-Picard said. "Many have shown that the stem cells in the dental pulp can become the cells of multiple tissues." Dr. Syed-Picard noted that the majority of the research is in the early stages. "Nevertheless, the studies show that these cells could have great potential for future regenerative therapies," she said. EW Editors' note: Dr. Syed-Picard has no financial interests related to this article. Contact information Syed-Picard: srikamav@upmc.edu "After injection in vivo into mouse corneal stroma, human DPSCs produced corneal stromal extracellular matrix containing hu- man type I collagen and keratocan and did not affect corneal transpar- ency or induce immunological rejection," Dr. Syed-Picard and colleagues reported. Indeed, the results are quite promising. Study findings demon- strated that DPSCs have the capacity to create engineered corneal stro- mal-like constructs with an orga- nized matrix similar to that of native corneal tissue. Also, data showed that human DPSCs have the ability to maintain their keratocyte phenotype after in vivo implantation into mouse corneas, indicating that the DPSCs secreted the appropriate matrix in the in vivo corneal stromal micro- environment without triggering rejection. All of these properties indicate that human DPSCs have potential use in regenerative corneal thera- pies. However, further studies are needed before investigations can be done on human subjects. "Our research is still in the early stages, and it will be years before the use of dental pulp stem cells for corneal restoration can be tested in humans," Dr. Syed-Picard said. "Ad- ditional studies need to be done in mice and in larger animals to prove efficacy and safety." Even with the current findings, further investigations are needed as more scientific questions come developmental origins," said Fatima N. Syed-Picard, PhD, postdoctoral associate, Department of Ophthal- mology, University of Pittsburgh, and lead author of the study. "This is why we thought that stem cells from the dental pulp might be able to become corneal cells." Autologous stem cells derived from other cranial neural crest tissues (such as the dental pulp) are postulated to have a strong affinity for differentiating into corneal cell types. "Human third molars (or wis- dom teeth) were opened and the dental pulp was removed," Dr. Syed-Picard said. "The pulp tissue was digested to isolate the cells, and the cells were cultured in a solution that directed them to become corne- al stromal cells." In this study, DPSCs were cul- tured in a solution that stimulated the cells to become keratocytes, the cells that are found in and maintain the corneal stroma. "Our studies show that dental pulp cells can be directed to express genes and proteins that are specific to cells of the corneal stroma— keratocytes," Dr. Syed-Picard said. "Because the dental cells are express- ing these markers, [this indicates] that they have differentiated into keratocytes." Dental pulp can be found in all human teeth. However, wisdom teeth were used in this study, Dr. Syed-Picard said, simply because they are routinely extracted and therefore easily obtained for research purposes. Dental pulp stem cells may be a new cellular source for the treatment of corneal blindness A dult dental pulp stem cells (DPSCs) isolated from human third molars or wisdom teeth are capable of differentiating into keratocytes, cells of the corneal stroma. The findings, recently published in Stem Cells Translational Medicine in March 2015 by researchers from the University of Pittsburgh, demon- strate the potential for the clinical application of DPSCs in cellular or tissue engineering therapies for human corneal scarring—a potential clinical approach to treating corneal blindness. Largely irreversible, corneal scarring is commonly treated with penetrating keratoplasty with allo- geneic cadaveric tissue. However, shortages in available donor tissue is now a worldwide issue. Additionally, many allogeneic grafts are eventually rejected by the host tissue. Statistically, corneal grafts have a failure rate of around 38% after 10 years, mainly due to tissue rejection, according to a 2006 study in the journal Transplantation. Thus, experts continue to look for an alternative approach. DPSCs as a potential cellular source In terms of personalized regenerative medicine, autologous stem cells are a potential alternative to cadaveric tissue grafts. Autologous stem cells that are capable of remodeling the corne- al tissue into the proper structure (without scarring) could bypass the limitation of current treatments. Someday, when engineered corneal stroma-like tissue constructs are generated from autologous stem cells to replace scarred tissue, sur- geons may no longer use cadaveric tissue grafts. Dental pulp includes adult stem cells, which are created embryoni- cally from the cranial neural crest, similar to corneal stroma. "The dental pulp and the corneal stroma have the same From dental pulp stem cells to corneal stromal regeneration " The dental pulp and the corneal stroma have the same developmental origins. This is why we thought that stem cells from the dental pulp might be able to become corneal cells. " –Fatima N. Syed-Picard, PhD

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