Characterization of a migrative subpopulation of adult human nasoseptal chondrocytes with progenitor cell features and their potential for in vivo cartilage regeneration strategies

Abstract

BackgroundProgenitor cells display interesting features for tissue repair and reconstruction. In the last years, such cells have been identified in different cartilage types. In this study, we isolated a migrative subpopulation of adult human nasoseptal chondrocytes with progenitor cell features by outgrowth from human nasal septum cartilage. These putative progenitor cells were comparatively characterized with mesenchymal stem cells (MSC) and human nasal septum chondrocytes with respect to their cellular characteristics as well as surface marker profile using flow cytometric analyses. Differentiation capacity was evaluated on protein and gene expression levels.ResultsThe migrative subpopulation differentiated into osteogenic and chondrogenic lineages with distinct differences to chondrocytes and MSC. Cells of the migrative subpopulation showed an intermediate surface marker profile positioned between MSC and chondrocytes. Significant differences were found for CD9, CD29, CD44, CD90, CD105 and CD106. The cells possessed a high migratory ability in a Boyden chamber assay and responded to chemotactic stimulation. To evaluate their potential use in tissue engineering applications, a decellularized septal cartilage matrix was either seeded with cells from the migrative subpopulation or chondrocytes. Matrix production was demonstrated immunohistochemically and verified on gene expression level. Along with secretion of matrix metalloproteinases, cells of the migrative subpopulation migrated faster into the collagen matrix than chondrocytes, while synthesis of cartilage specific matrix was comparable.ConclusionsCells of the migrative subpopulation, due to their migratory characteristics, are a potential cell source for in vivo regeneration of nasal cartilage. The in vivo mobilization of nasal cartilage progenitor cells is envisioned to be the basis for in situ tissue engineering procedures, aiming at the use of unseeded biomaterials which are able to recruit local progenitor cells for cartilage regeneration.

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

“…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. More recently, a population of nasoseptal chondrocytes with progenitor features were described by Rotter and co-workers [31].…”

Toward tissue-engineering of nasal cartilages

“…It has also been suggested that the superficial zone of septal cartilage contains a promising population of nasoseptal progenitor cells (NSPs) [108]. These cells are migratory and express surface markers, such as CD29, CD105, CD106, CD90, and CCD44, suggesting a state of differentiation between mesenchymal stem cells (MSCs) and chondrocytes [109]. NSPs have been shown to differentiate to chondrogenic and osteogenic, but not adipogenic lineages [88] and show a greater proliferation potential than bone marrow-and adipose-derived MSCs [110].…”

The functional role of chondrogenic stem/progenitor cells: novel evidence for immunomodulatory properties and regenerative potential after cartilage injury

“…A migratory cartilage-resident cell population, also referred to as CSPCs, has gained attention due to its beneficial localisation and innate chondrogenic phenotype, reflected in superior chondrogenic differentiation capacities as compared to BM-MSCs (Jiang and Tuan, 2015;Xue et al, 2016). Moreover, CSPCs possess multipotent differentiation capacities and a surface marker expression profile similar to that of BM-MSCs, including the minimal criteria, commonly used to identify MSCs (Dominici et al, 2006;Joos et al, 2013). This makes CSPCs a promising target to improve intrinsic healing of cartilage defects but also in terms of tissue engineering (Elsaesser et al, 2016;Jiang and Tuan, 2015).…”

“…Moreover, CSPCs possess multipotent differentiation capacities and a surface marker expression profile similar to that of BM-MSCs, including the minimal criteria, commonly used to identify MSCs (Dominici et al, 2006;Joos et al, 2013). This makes CSPCs a promising target to improve intrinsic healing of cartilage defects but also in terms of tissue engineering (Elsaesser et al, 2016;Jiang and Tuan, 2015). CSPCs are attracted by DAMPs, such as HMGB1 (Seol et al, 2012), and signalling molecules, comprising SDF-1 (Yu et al, 2015), IGF-1 and PDGF (Joos et al, 2013).…”