Bone-forming capacity of adult human nasal chondrocytes.

Benjamin E Pippenger,Arnaud Scherberich,Ivan Martin,Sandra Feliciano,Karoliina Pelttari,X Frank Walboomers,Claude Jaquiery,Manuela Ventura,Andrea Barbero

doi:10.1111/jcmm.12526

Abstract

Nasal chondrocytes (NC) derive from the same multipotent embryological segment that gives rise to the majority of the maxillofacial bone and have been reported to differentiate into osteoblast-like cells in vitro. In this study, we assessed the capacity of adult human NC, appropriately primed towards hypertrophic or osteoblastic differentiation, to form bone tissue in vivo. Hypertrophic induction of NC-based micromass pellets formed mineralized cartilaginous tissues rich in type X collagen, but upon implantation into subcutaneous pockets of nude mice remained avascular and reverted to stable hyaline-cartilage. In the same ectopic environment, NC embedded into ceramic scaffolds and primed with osteogenic medium only sporadically formed intramembranous bone tissue. A clonal study could not demonstrate that the low bone formation efficiency was related to a possibly small proportion of cells competent to become fully functional osteoblasts. We next tested whether the cues present in an orthotopic environment could induce a more efficient direct osteoblastic transformation of NC. Using a nude rat calvarial defect model, we demonstrated that (i) NC directly participated in frank bone formation and (ii) the efficiency of survival and bone formation by NC was significantly higher than that of reference osteogenic cells, namely bone marrow-derived mesenchymal stromal cells. This study provides a proof-of-principle that NC have the plasticity to convert into bone cells and thereby represent an easily available cell source to be further investigated for craniofacial bone regeneration.

Highlights

Cells from the adult nasal septum derive from the same multipotent embryological segment that gives rise to the majority of the bone and cartilage of the head and face [1]
The resulting tissues displayed clear cartilaginous features, including positive Safranin-O staining for glycosaminoglycans (GAG) (Fig. 1A) and large cells in lacunae embedded in abundant, mineral free matrix positive for collagen type II (COLL II)
The expression of genes encoding for the above proteins matched the immunohistochemical findings and paralleled the expression profiles found in bone marrow-derived mesenchymal stromal cells (BMSC) undergoing the same culture regime, including up-regulation of bone sialoprotein (BSP) and COLL-10 (Fig. 1E)

Summary

Introduction

Cells from the adult nasal septum (nasal chondrocytes, NC) derive from the same multipotent embryological segment that gives rise to the majority of the bone and cartilage of the head and face (neural crest/neuroectoderm) [1]. Human septal cartilage has long been considered the pacemaker for the growth of the face and skull, with growth potential equivalent to that of the epiphyseal growth cartilage of long bones [2]. In vitro studies have demonstrated that NC retain a certain level of plasticity and can acquire traits of neuronal- and osteoblast-like phenotypes [4, 5]. It is unknown if NC can induce or directly from frank bone tissue in vivo.

Methods

Results

Conclusion