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Rodriguez. Plast Aesthet Res 2023;10:67 https://dx.doi.org/10.20517/2347-9264.2023.73 Page 5 of 18

Figure 2. Experiments that illustrate RIBE. (A) A well of cultured fibroblasts (in green) was covered with Mylar dishes equipped with
shutters (black) that left 1% of the cells exposed to irradiation (yellow strips). After several days of culture, 30% of cells showed
changes typical of radiation damage [10] ; (B) To determine if this effect was cell contact-dependent, a separate group of investigators
irradiated cultured fibroblasts (red vertical hash pattern). After irradiation, they placed the irradiated fibroblasts in a well with
unirradiated fibroblasts (blue divots, white background). The two cell preparations were separated by a permeable mesh (black mesh
pattern) that allowed media exchange but no cell contact. After co-culture, the unirradiated fibroblasts showed cytoplasmic and
[11]
chromatid changes typical of radiation damage .

Figure 3. (A) “Target cell” mechanism of injury. Ionizing Radiation damages nuclear cell DNA. The cell responds by repairing itself
successfully, whereas a faulty repair can result in survival with an unstable genome or apoptosis; (B) RIBE (radiation induced bystander
effect)- Ionizing radiation damages any portion of the cell which can then release molecular compounds (DAMPS- damage associated
macromolecular patterns) that act as “danger signals” to neighboring cells. These compounds may even cause chromatin changes in
adjacent non-irradiated cells. The bystander cell responds by repairing itself successfully, whereas a faulty repair can result in survival
with an unstable genome or apoptosis; (C) Ionizing radiation liberates matrix-embedded cytokines (TGF-β) that can then influence
surrounding cells. Bystander cell behavior may then be “reprogrammed” by active TGF-β into undergoing apoptosis, EMT (epithelial to
mesenchymal transformation), or mitotic arrest of the cell cycle at the G1 phase.

inflammatory reaction . The main effector cell of the regenerative response is the Mesenchymal Stem
[14]
cell [15-17] .

The remodeling phase concludes the wound healing response. The effector cell of the remodeling phase is
the fibroblast. Unlike the inflammatory or regenerative responses, it does not have much of a proliferative
component. Like the inflammatory response, it has a prominent apoptotic function, but it is directed at
paring off excess tissue created by the regenerative phase.