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 Alexa647-HA-PE penetrated into the epidermis and dermis, where it associated with both keratinocytes and fibroblasts. In contrast, Alexa647-HA was largely retained in the outer cornified layer of the epidermis and quantification of fluorescence confirmed that significantly more Alexa647-HA-PE penetrated into and was retained within the epidermis than Alexa647-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.

Hyaluronan Hybrid Cooperative Complexes as a Novel Frontier for Cellular Bioprocesses Re-Activation

“…As for skin homeostasis, the reduction of HA may lead to physiological alterations of keratinocytes and fibroblasts [ 15 , 16 ]. The use of HA moderately improved epidermal homeostasis barrier and tissue thickness in murine models [ 17 ]. Since the early 1980s, all these data has led to the extensive use of HA injections for correction of wrinkles and rejuvenation procedures [ 12 ].…”

Carcinoma Cell Hyaluronan as a “Portable” Cancerized Prometastatic Microenvironment

“…Extruded high molecular weight HA polymers are initially captured by cellular HA receptors and are assembled and stabilized into pericellular coats by a family of extracellular HA binding proteins including tenascin, inter-alpha-trypsin inhibitor, versican, and TSG-6 [6–8]. These HA rich pericellular matrices are easily visualized in culture as pericellular coats [9] and are also clearly present in vivo [10, 11]. In primary tumors, the cancerized stroma is a rich source of growth factors and cytokines that both stimulate HA synthesis and enhance carcinoma survival and progression.…”

Lattice percolation approach to numerical modelling of tissue aging

“…Cells, such as skin cells, are obviously not fully regular, and their shapes are also not symmetrical with respect to their arrangement in the tissue [63]. Assessing the histological preparation of epidermis [71], however, one can argue that lattice-type ordering makes a good approximation for evaluating average quantities, especially considering that we are not interested in long-range fluctuations and correlations. Before discussing this matter further, let us mention a potential experimental setup for verifying percolation model approach and predictions, illustrated in Fig.…”