Bone‐forming capacity of adult human nasal chondrocytes

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.

Generation of a Bone Organ by Human Adipose-Derived Stromal Cells Through Endochondral Ossification

“…In this context, it is relevant to remark that the formation of a hypertrophic cartilaginous template by other cell sources is not always sufficient to initiate ECO in vivo. This was recently demonstrated with chondrogenically reprogrammed dermal fibroblasts by constitutive expression of Sox9, Klf4, and c‐Myc [33], as well as with nasal chondrocytes [34]. Taken together, these results indicate that ASC, although requiring distinct conditions to enter chondrogenesis, which may be related to their epigenetic signature [8], have the ability to execute an ECO program, as opposed to phenotypically stable chondrocytes.…”

Bone physiology as inspiration for tissue regenerative therapies

“…However, the application of stem cells from abundant and easily retrievable sources is potentially highly valuable. This hypothesis is reinforced by the failure of primary chondrocyte lineages - including fully mature nasal chondrocytes induced in vitro for an hyperthrophic phenotype – on being capable of leading in vivo endochondral ossification; in opposition, implanted tissues prepared from hyperthrophic nasal chondrocytes reverted their phenotype into a hyaline status [86]. In 2016, ASCs assembled as 3D cellular micrometric pellets or adhered onto collagen scaffolds were cultured in chondrogenic cell culture media supplemented with early and, optionally, with late hyperthropic supplements administered on later times of in vitro culture [87].…”

Repair of bone defects in vivo using tissue engineered hypertrophic cartilage grafts produced from nasal chondrocytes

“…In addition, chondrocytes extracted from the nasal septum have been broadly studied in tissue engineering for their capacity to produce a hyaline cartilage matrix [24,[27][28][29] and have been used clinically for repair of septal defects [17]. Only one detailed in vivo study to date has considered the use of nasal chondrocytes for tissue engineering a hypertrophic cartilage template for bone regeneration [30]. Here engineered constructs did not mineralise following M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 8 sub-cutaneous implantation, but were capable of some mineralisation following osteogenic pre-culture and implantation within ceramic scaffolds.…”