Dermal Papilla Cells improve the wound healing process and generate hair bud-like structures in grafted skin substitutes using Hair Follicle Stem Cells

Authors
Leiros, Gustavo Jose; Kusinsky, Ana Gabriela; Drago, Hugo; Bossi, Silvia; Sturla, Flavio; Castellanos, Maria Lia; Stella, Inés Yolanda; Balaña, Maria Eugenia
Publication Year
2014
Language
English
Format
article
Status
Published version
Description
Tissue-engineered skin represents a useful strategy for the treatment of deep skin injuries and may contribute to the understanding of skin regeneration. The growth of hair follicles in vitro or after grafting remains a major challenge. The dermal-epidermal composites are skin substitutes comprised of dermal fibroblasts (DF) embedded in a matrix overlaid with keratinocytes. Hair Follicle Stem Cells (HFSC) contribute to hair follicle regeneration and wound repair. Dermal papilla cells (DPC) signaling orchestrates hair follicle morphogenesis and regeneration. The use of DPC as dermal component in a permanent composite skin with human HFSC was evaluated by studying tissue-engineered skin architecture, stem cell persistence and hair regeneration as well as the graft-take in nude mice. A porcine acellular dermal matrix (ADM) was seeded with HFSC alone and with human DPC or DF. Histological and immunohistochemical analyses of in vitro constructs were performed. The presence of DPC induced a more regular and multi-layered stratified epidermis with more basal p63-positive cells and invaginations. Graft-take and tissue remodeling in nude mice were favored in DPC-containing composite skin supported by the fact of graft-epidermis survival and early neovascularization. Interestingly, only in grafted constructs containing DPC, embryonic hair bud-like structures were observed from 14 days after grafting. These structures showed cells of human origin, presence of precursor epithelial cells and expression of a hair differentiation marker. These observations suggest an incipient hair follicle neogenesis inside the remodeling ADM. Taken together our results show DPC and HFSC as promising cellular components for a permanent skin substitute.
Fil: Leiros, Gustavo Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencias y Tecnología "Dr. Cesar Milstein"; Argentina
Fil: Kusinsky, Ana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencias y Tecnología "Dr. Cesar Milstein"; Argentina
Fil: Drago, Hugo. Hospital de Quemados de la Ciudad de Buenos Aires. Banco de Tejidos; Argentina
Fil: Bossi, Silvia. Hospital de Quemados de la Ciudad de Buenos Aires. Banco de Tejidos; Argentina
Fil: Sturla, Flavio. Hospital de Quemados de la Ciudad de Buenos Aires. Banco de Tejidos; Argentina
Fil: Castellanos, Maria Lia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencias y Tecnología "Dr. Cesar Milstein"; Argentina
Fil: Stella, Inés Yolanda. Universidad Maimónides. Centro de Estudios Biomédicos, Ambientales y Diagnóstico; Argentina
Fil: Balaña, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencias y Tecnología "Dr. Cesar Milstein"; Argentina
Subject
Skin substitutes
Dermal papilla cells
Hair follicle neogenesis
Hair follicles stem cells
Otras Biotecnologías de la Salud
Biotecnología de la Salud
CIENCIAS MÉDICAS Y DE LA SALUD
Access level
Restricted access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/4110