Schwann Cell Phenotype Changes in Aging Human Dental Pulp

Abstract

Schwann cells are glial cells that support axonal development, maintenance, defense, and regeneration in the peripheral nervous system. There is limited knowledge regarding the organization, plasticity, and aging of Schwann cells within the dental pulp in adult permanent teeth. The present study sought to relate changes in the pattern of Schwann cell phenotypes between young and old adult teeth with neuronal, immune, and vascular components of the dental pulp. Schwann cells are shown to form a prominent glial network at the dentin-pulp interface, consisting of nonmyelinating and myelinating phenotypes, forming a multicellular neuroimmune interface in association with nerve fibers and dendritic cells. Schwann cell phenotypes are recognized by the expression of S100, glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), Sox10, GAP43, and p75NTR markers. In young adult teeth, a dense population of nonmyelinating Schwann cells projects processes in close association with sensory nerve terminals through the odontoblast layer, reaching the adjacent predentin/dentin domain. While GAP43 and p75NTR are highly expressed in nonmyelinating Schwann cells from young adult teeth, the presence of these markers declines significantly in old adult teeth. Myelinated axons, identified by MBP expression, are mainly present at the Raschkow plexus and within nerve bundles in the dental pulp, but their density is significantly reduced in old adult versus young adult teeth. These data reveal age-related changes within the glial network of the dental pulp, in association with a reduction of coronal dental pulp innervation in old adult versus young adult teeth. The prominence of Schwann cells as a cellular component at the dentin-pulp interface supports the notion that their association with sensory nerve terminals and immune system components forms part of an integrated multicellular barrier for defense against pathogens and dentin repair.

Neuronal substrates alter the migratory responses of nonmyelinating Schwann cells to controlled brain‐derived neurotrophic factor gradients

“…Regenerative strategies rely strongly upon the local migration of replacement and/or supplemental cells (Mishra, Pena, Redenti, & Vazquez, ; Thakur et al, ), which requires detailed knowledge of cell migratory capacity and response(s). Although cell replacement therapies using terminal SCs remain elusive (Couve, Lovera, Suzuki, & Schmachtenberg, ), SC migration has been reported to aid axonal regeneration and synaptic SC–MN connections during transplantation of SCs, individually and in combination with different stem‐like cells and biomaterials (Ban et al, ; Hyung et al, ; Jones et al, ; Xia et al, ; Xie et al, ; Yang et al, ; Zeng et al, ; Zhang et al, ). As a result, our study examined the concurrent use of neurotrophin gradients and neuronal substrates to stimulate migratory behaviors of nmSCs via both chemical stimulus and haptotactic pathways (Figure ).…”

Schwann Cell Responses and Plasticity in Different Dental Pulp Scenarios

“…While the early emergence and evolution of dentin in primitive vertebrates has been related to a nascent sensory function of the DP (Smith and Sansom, 2000 ; Farahani et al, 2011 ), it is attractive to hypothesize that in mammalian teeth, the limited replacement and increased longevity of dentition required an enlargement and an increased complexity of the DP, in which odontoblasts, sensory nerve endings and Schwann cells (SCs), in association with immune and vascular components, create a multicellular interface, which fulfills critical functions in sensory protection, defense and repair of the tooth (Figures 1A,B ). Thus, nerves, glial and immune components interact to sense and respond to external stimuli and changes at the dentin-pulp interface (Couve et al, 2014 , 2018 ).…”

“…The expression of NGF receptors (NGFR), like the p75 neurotrophin receptor (p75NTR) is up-regulated by SCs in injured nerves. Non-mSCs classically referred to as Remak SCs play important roles in trophic support and plasticity of terminal axons through the expression of neurotrophin receptors, like p75NTR (Couve et al, 2018 ).…”

“…At the dentin-pulp interface of human teeth, SCs are integrated within a complex multicellular organization together with sensory nerve endings and immunocompetent cells (dendritic cells), suggesting a concerted function in the defense against pathogens, dentin repair and regeneration (Couve et al, 2018 ). At the main barrier surfaces of the body (i.e., skin, gut, airways), nerve fibers and immune cells form sensory interfaces able to detect pathogens and mediate responses to tissue-specific environmental changes (Veiga-Fernandes and Mucida, 2016 ).…”

“…Scale bars: (A–D) , 50 μm; (E,F) , 10 μm. (C) , modified from Suzuki et al ( 2015 ); (D) modified from Couve et al ( 2014 ); (E,F) modified from Couve et al ( 2018 ).…”