Growth factor mimetics for skin regeneration: In vitro profiling of primary human fibroblasts and keratinocytes. Issue 8 (8th May 2021)

• Record Type: Journal Article
• Authors: Horinouchi, Cintia D. S.; Oostendorp, Corien; Schade, Dennis; van Kuppevelt, Toin H.; Daamen, Willeke F.
• Is Part Of: Archiv der Pharmazie. Volume 354:Issue 8(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-05-08
• Subjects: ONO‐1301 -- purmorphamine -- small molecules -- SUN11602 -- wound healing; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.202100082
• Languages: English
• ISSNs: 0365-6233

Abstract

Abstract: Small molecules have gained considerable interest in regenerative medicine, as they can effectively modulate cell fates in a spatiotemporal controllable fashion. A continuous challenge in the field represents genuine mimicry or activation of growth factor signaling with small molecules. Here, we selected and profiled three compounds for their capacity to directly or indirectly activate endogenous FGF‐2, VEGF, or SHH signaling events in the context of skin regeneration. Phenotypic and functional analysis of primary skin fibroblasts and keratinocytes revealed unique, cell‐specific activity profiles for the FGF‐2 mimetic SUN11602 and the putative VEGF mimetic ONO‐1301. Whereas SUN11602 exclusively stimulated keratinocyte differentiation, ONO‐1301 mainly affected the proliferation and migration behavior of fibroblasts. In each skin cell type, both compounds selectively enhanced the expression of MMP1 and VEGFA . A combined small molecule FGF‐2/VEGF mimicry may not only improve angiogenesis‐related microcirculation but also reduce early fibrosis while facilitating wound remodeling at later stages. SUN11602 and ONO‐1301 represent valuable tools for improving the management of difficult‐to‐heal wounds, particularly for the design and development of small molecule‐functionalized, next‐generation, engineered skin substitutes. Abstract : The small molecule FGF‐2 signaling mimetic SUN11602 and the prostacyclin‐agonistic VEGF mimetic ONO‐1301 induce cell type‐specific regenerative responses in primary skin cells for potential use in functionalized engineered skin substitutes.