Isolation and Culture of Human Stem Cells from Apical Papilla under Low Oxygen Concentration Highlight Original Properties

Abstract

Stem cells isolated from the apical papilla of wisdom teeth (SCAPs) are an attractive model for tissue repair due to their availability, high proliferation rate and potential to differentiate in vitro towards mesodermal and neurogenic lineages. Adult stem cells, such as SCAPs, develop in stem cell niches in which the oxygen concentration [O 2 ] is low (3-8% compared with 21% of ambient air). In this work, we evaluate the impact of low [O 2 ] on the physiology of SCAPs isolated and processed in parallel at 21% or 3% O 2 without any hyperoxic shock in ambient air during the experiment performed at 3% O 2 . We demonstrate that SCAPs display a higher proliferation capacity at 3% O 2 than in ambient air with elevated expression levels of two cell surface antigens: the alpha-6 integrin subunit (CD49f) and the embryonic stem cell marker (SSEA4). We show that the mesodermal differentiation potential of SCAPs is conserved at early passage in both [O 2 ], but is partly lost at late passage and low [O 2 ], conditions in which SCAPs proliferate efficiently without any sign of apoptosis. Unexpectedly, we show that autophagic flux is active in SCAPs irrespective of [O 2 ] and that this process remains high in cells even after prolonged exposure to 3% O 2 .

Unraveling the Role of the Apical Papilla During Dental Root Maturation

“…Gene expression analysis has proven that disruption of the micro-environmental niche leads to high number of differentially expressed genes when compared between tissue and SCAP in culture ( Diao et al, 2017 ). SCAP from early passage have been shown to retain a more original phenotype as demonstrated by their intact mesodermal differentiation capacity ( Rémy et al, 2019 ). A similar observation was made when studying Wnt inhibitory factor 1 (WIF1) expression, a Wnt/β-catenin modulator which maintains stem cell commitment ( Wang and Cao, 2019 ).…”

Dental Stem Cell Banking and Applications of Dental Stem Cells for Regenerative Medicine

“…They call for future research to be conducted regarding the immunogenicity of the cells and suggest that SCAP may be an ideal candidate for stem cell banking [15]. Current research focuses on identifying the precise biomaterials that make up the environment in which SCAP best contributes to tissue regeneration such as oxygen level [43] and ideal makeup of a transplant carrier [44,45].…”

Therapeutic Functions of Stem Cells from Oral Cavity: An Update

“…In 2006, it was first reported that the apical papilla is another dental stem/progenitor cell source for so-called 'stem cells from the apical papilla (SCAPs)' [81]. SCAPs can be isolated from the apical papilla via single-cell culture after enzymatic dissociation or organotypic tissue culture method [81,82]. The established clonogenic SCAPs have typical characteristics of other dental MSCs in terms of immunophenotype, self-renewal, and differentiation capacity; however, they also exhibit various unique as well as superior properties for clinical application as described below.…”