Stem cell marker upregulation in normal cutaneous vessels following pulsed-dye laser exposure and its abrogation by concurrent rapamycin administration: implications for treatment of port-wine stain birthmarks.
Port-wine stains (PWS) represent a group of vascular malformations that are usually accompanied by psychological distress for affected patients, often reflected in high treatment demand. Although the pulsed-dye laser (PDL) was established as standard therapy for PWS more than a decade ago, therapeutic outcome may be unsatisfactory. One of the main drawbacks to successful PDL therapy is PWS revascularization shortly after laser exposure. Therefore, inhibition of revascularization should improve therapeutic outcome of PDL therapy. In this study, we first evaluated the effects of various light energies on normal cutaneous vessels over a period of 14 days, particularly the proliferation and stem cell marker expression of dermal endothelial cells, which were found to be highest 8 days following laser exposure. We found that PDL exposure induced dose-dependent damage of dermal vessels up to energy densities of 6 J/cm(2), above which no increase in PDL-induced effects were observed with the energies employed in this study. In dermal endothelial cells of PDL-exposed skin, we found strong expression of the proliferation marker Ki-67 as well as the stem cell marker nestin but not other stem cell markers such as CD133 and CD166. The influence of rapamycin (RPM), used as an adjuvant to PDL exposure, was also investigated. RPM administration reduced Ki-67 and nestin expression in dermal endothelial cells and increased PDL-induced destruction of dermal vessels, indicating that the use of RPM after PDL exposure may be an interesting new approach for prolonging and improving PWS laser therapeutic outcome.
Loewe
Robert
R
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Oble
Darryl A
DA
Valero
Teresa
T
Zukerberg
Lawrence
L
Mihm
Martin C
MC
Nelson
J Stuart
JS
D000071916:AC133 Antigen; D000287:Administration, Topical; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D015703:Antigens, CD / Q000378:metabolism; D001706:Biopsy; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002455:Cell Division / Q000528:radiation effects; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D005326:Fetal Proteins / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D053685:Laser Therapy / Q000009:adverse effects / Q000379:methods*; D054025:Lasers, Dye / Q000009:adverse effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D010455:Peptides / Q000378:metabolism; D019339:Port-Wine Stain / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D012008:Recurrence; D020123:Sirolimus / Q000008:administration & dosage*; D012867:Skin / Q000098:blood supply / Q000166:cytology / Q000528:radiation effects; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D015854:Up-Regulation / Q000187:drug effects / Q000528:radiation effects; D020410:Activated-Leukocyte Cell Adhesion Molecule
D000071916:AC133 Antigen; D000903:Antibiotics, Antineoplastic; D015703:Antigens, CD; D015816:Cell Adhesion Molecules, Neuronal; D005326:Fetal Proteins; D006023:Glycoproteins; D007381:Intermediate Filament Proteins; D019394:Ki-67 Antigen; D009419:Nerve Tissue Proteins; D064231:Nestin; D010455:Peptides; D020123:Sirolimus; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule; C577484:NES protein, human; C000606023:PROM1 protein, human