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A tooth for an eye
DURHAM, N.C.—A team from the University of Pittsburgh, led by Drs. James L. Funderburgh and Fatima Syed-Picard of the department of ophthalmology, have investigated adult dental pulp stem cells (DPSC) as a potential solution to blindness—specifically, corneal scarring. The findings were published in STEM CELLS Translational Medicine in a paper titled “Dental Pulp Stem Cells: A New Cellular Resource for Corneal Stromal Regeneration.”
As noted in a paper published in Stem Cell Reviews in 2008—“Dental pulp stem cells: a promising tool for bone regeneration”—DPSCs are an ideal source of stem cells, as “access to the collection site of these cells is easy and produces very low morbidity; extraction of stem cells from pulp tissue is highly efficiency; they have an extensive differentiation ability; and the demonstrated interactivity with biomaterials makes them ideal for tissue reconstruction.” The abstract adds that a number of studies have shown DPSCs to be “multipotent stromal cells that can be safety cryopreserved, used with several scaffolds, that can extensively proliferate [and] have a long lifespan.” In addition, “they seem to possess immunoprivileges as they can be grafted into allogenic tissues and seem to exert anti-inflammatory abilities, like many other mesenchymal stem cells.”
“If we could generate an engineered cornea using autologous cells, which are the patient’s own cells, and then use that to replace scarred tissue, we could bypass the limitations of current treatments,” Funderburgh explained. “We thought dental pulp might be the answer, as other studies have proven that DPSCs can differentiate into various other cells and they already have a similarity to cornea tissue as they both develop in the embryo stage from the cranial neural crest. That led us to believe that we might induce DPSCs to become corneal cells, too.”
The DPSCs were harvested from molar teeth that had been extracted in routine procedures at the University of Pittsburgh's dental school, then treated with a special solution that caused them to differentiate into corneal cells, also known as keratocytes. The DPSC-generated keratocytes were found to have the same properties as those that grow naturally in the human eye; as elaborated in the paper's abstract, “After inducing differentiation in vitro, DPCs expressed molecules characteristic of keratocytes, keratocan and keratan sulfate proteoglycans at both the gene and the protein levels.” The generated keratocytes were seeded onto a corneal-shaped nanofiber substrate, and four weeks later had grown into a structure that mimicked the organization of a natural cornea.
The team then evaluated the performance of the manufactured keratocytes by labeling them with a dye and injecting them into the right eyes of mouse models, while the left eyes were injected with medium only to serve as a control. After five weeks they tested the mice's eyes and found that not only did the generated keratocytes remain in the corneas and behave similarly to their natural counterparts, the corneas were clear and showed no signs of rejection.
“Shortages of donor corneas and rejection of donor tissue do occur, which can result in permanent vision loss,” said Funderburgh. “Our work is promising because using the patient’s own cells for treatment could help us avoid these problems.”
“Other research has shown that dental pulp stem cells can be used to make neural, bone and other cells,” Syed-Picard added. “They have great potential for use in regenerative therapies.”
Future work will include determining whether this approach can also correct corneal scarring in animal models.
Corneal blindness is the result of the cornea becoming scarred and cloudy, which prohibits light from reaching the retina. Corneal scarring is irreversible for the most part, so the prevailing treatment method is to graft a new cornea constructed from cadaver tissue. However, as is often the case with organ transplants, many of these grafts are eventually rejected as the body registers them as foreign tissue; at present, the failure rate of corneal grafts is roughly 38 percent after 10 years, which is attributed primarily to tissue rejection.