Sun Exposure Damages Skin-Derived Stem Cells in Porphyria Patient

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by Joana Carvalho |

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sun exposure, porphyria

Sun exposure may lower the number and affect the properties of skin-derived stem cells in people with variegate porphyria, particularly their ability to give rise to other cell types, a study in two people has found.

Further studies are still needed to understand the mechanisms that may cause the negative effects associated with sun exposure, the researchers said.

The study, “Comparative characterization of sun exposed and sun protected skin-derived mesenchymal-like stem cells in variegate porphyria and healthy individuals,” was published in the journal Photodermatology, Photoimmunology & Photomedicine.

Variegate porphyria is a hepatic form of porphyria caused by mutations in the PPOX gene, which provides instructions for making an enzyme called protoporphyrinogen oxidase. This is one of the eight enzymes needed for the production of heme, a molecule essential for red blood cells to transport oxygen and for the breakdown of compounds in the liver.

Sunlight sensitivity caused by the buildup of porphyrins (heme precursors) on the skin is one of the hallmarks of variegate porphyria. Previous studies have also shown that porphyrins increase sunlight skin absorption, resulting in the production of harmful oxidant molecules and promoting tissue inflammation, premature aging, and DNA damage.

Based on these observations, investigators at the American University of Beirut in Lebanon led a study that hypothesized that sun exposure might have a negative impact on skin-derived mesenchymal stem cells — a subpopulation of adult stem cells — in people with porphyria.

To test this hypothesis, the team assessed the properties of mesenchymal‐like stem cells isolated from skin samples taken from the lower back, considered a sun-protected area, and the back of the hand, a sun-exposed area, of a 16-year-old patient with variegate porphyria and an 18-year-old healthy individual.

To evaluate the cells’ ability to expand and migrate, the researchers cultivated them in a lab dish in the presence of an antioxidant molecule called N‐acetylcysteine. They also looked at the cells’ ability to grow into other cell types — in this case, osteoblasts (bone-forming cells).

Results first showed that mesenchymal‐like stem cells from the patient, especially those isolated from skin areas exposed to sunlight, had lower levels of the stem cell marker CD105 than those taken from the healthy person (1.4% vs. 5%). These approximately 3.5 times lower levels in the patient are “probably attributed to cell death triggered by the disease itself,” the scientists wrote.

Interestingly, they found that mesenchymal‐like stem cells isolated from the patient’s hand retained their ability to self-renew and did so at a faster pace than those isolated from the healthy individual.

However, when grown in a special culture medium, the patient’s mesenchymal‐like stem cells were less able to grow into bone-forming cells. This was true for cells isolated from sun-protected and sun-exposed skin areas.

According to the investigators, these observations suggest the remaining stem cells isolated from the patient’s hand became more primed to maintain their ability to self-renew in an attempt to counteract the effects of the disease, to the detriment of their ability to give rise to other cell types.

Further experiments also revealed that cells isolated from sun-exposed areas in the patient were less efficient at migrating in a wound-healing lab assay than those isolated from sun-protected areas. Cultivating patient cells isolated from sun-exposed areas in the presence of N‐acetylcysteine also did not result in any noticeable benefits.

“In conclusion, the pool of mesenchymal stem-like [sun exposed] cells is affected in variegate porphyria patient along with modification of their self‐renewal and differentiation properties,” the investigators wrote. “Further studies are needed to understand the significance of the difference between these two areas in a bid to correct the sun-induced damage in the affected areas.”