title: Hyaluronan-phosphatidylethanolamine polymers form pericellular coats on keratinocytes and promote basal keratinocyte proliferation.
abstract: Aged keratinocytes have diminished proliferative capacity and hyaluronan (HA) cell coats, which are losses that contribute to atrophic skin characterized by reduced barrier and repair functions. We formulated HA-phospholipid (phosphatidylethanolamine, HA-PE) polymers that form pericellular coats around cultured dermal fibroblasts independently of CD44 or RHAMM display. We investigated the ability of these HA-PE polymers to penetrate into aged mouse skin and restore epidermal function in vivo. Topically applied Alexa(647)-HA-PE penetrated into the epidermis and dermis, where it associated with both keratinocytes and fibroblasts. In contrast, Alexa(647)-HA was largely retained in the outer cornified layer of the epidermis and quantification of fluorescence confirmed that significantly more Alexa(647)-HA-PE penetrated into and was retained within the epidermis than Alexa(647)-HA. Multiple topical applications of HA-PE to shaved mouse skin significantly stimulated basal keratinocyte proliferation and epidermal thickness compared to HA or vehicle cream alone. HA-PE had no detectable effect on keratinocyte differentiation and did not promote local or systemic inflammation. These effects of HA-PE polymers are similar to those reported for endogenous epidermal HA in youthful skin and show that topical application of HA-PE polymers can restore some of the impaired functions of aged epidermis.
authors.affiliation: Division of Plastic and Reconstructive Surgery, University of Western Ontario, 1151 Richmond Street, London, ON, Canada N6A 3K7.
authors.forename: Caitlin J
authors.initials: CJ
authors.lastname: Symonette
authors.affiliation: London Regional Cancer Program, London Health Sciences Centre, Room A4-931A, 790 Commissioners Road East, London, ON, Canada N6A 4L6.
authors.forename: Aman
authors.identifier: 0000-0001-5958-7051
authors.initials: A
authors.lastname: Kaur Mann
authors.affiliation: London Regional Cancer Program, London Health Sciences Centre, Room A4-931A, 790 Commissioners Road East, London, ON, Canada N6A 4L6.
authors.forename: Xiao Cherie
authors.initials: XC
authors.lastname: Tan
authors.affiliation: London Regional Cancer Program, London Health Sciences Centre, Room A4-931A, 790 Commissioners Road East, London, ON, Canada N6A 4L6.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Tolg
authors.affiliation: London Regional Cancer Program, London Health Sciences Centre, Room A4-931A, 790 Commissioners Road East, London, ON, Canada N6A 4L6.
authors.forename: Jenny
authors.initials: J
authors.lastname: Ma
authors.affiliation: London Regional Cancer Program, London Health Sciences Centre, Room A4-931A, 790 Commissioners Road East, London, ON, Canada N6A 4L6.
authors.forename: Francisco
authors.initials: F
authors.lastname: Perera
authors.affiliation: Division of Plastic and Reconstructive Surgery, University of Western Ontario, 1151 Richmond Street, London, ON, Canada N6A 3K7 ; London Health Science Center, Victoria Hospital, Room E2-647, 800 Commissioners Road East, London, ON, Canada N6A 4G5.
authors.forename: Arjang
authors.identifier: 0000-0001-9865-283X
authors.initials: A
authors.lastname: Yazdani
authors.affiliation: Division of Plastic and Reconstructive Surgery, University of Western Ontario, 1151 Richmond Street, London, ON, Canada N6A 3K7 ; London Regional Cancer Program, London Health Sciences Centre, Room A4-931A, 790 Commissioners Road East, London, ON, Canada N6A 4L6.
authors.forename: Eva A
authors.initials: EA
authors.lastname: Turley
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000172:deficiency / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000494:pharmacology*; D007249:Inflammation / Q000473:pathology; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D010714:Phosphatidylethanolamines / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology*
chemical_list: D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; D010714:Phosphatidylethanolamines; D011108:Polymers; C098946:hyaluronan-mediated motility receptor; C483858:phosphatidylethanolamine; D006820:Hyaluronic Acid