Abstract
BackgroundSince cartilage-derived stem/progenitor cells (CSPCs) were first identified in articular cartilage using differential adhesion to fibronectin, their self-renewal capacity and niche-specific lineage preference for chondrogenesis have propelled their application for cartilage tissue engineering. In many adult tissues, stem/progenitor cells are recognised to be involved in tissue homeostasis. However, the role of nasoseptal CSPCs has not yet been elucidated. Our aim was to isolate and characterise nasoseptal CSPCs alongside nasoseptal chondrocyte populations and determine chondrogenic capacity.MethodsHere, we isolated nasoseptal CSPCs using differential adhesion to fibronectin and assessed their colony forming efficiency, proliferation kinetics, karyotype and trilineage potential. CSPCs were characterised alongside non-fibronectin-adherent nasoseptal chondrocytes (DNCs) and cartilage-derived cells (CDCs, a heterogenous combination of DNCs and CSPCs) by assessing differences in gene expression profiles using PCR Stem Cell Array, immunophenotype using flow cytometry and chondrogencity using RT-PCR and histology.ResultsCSPCs were clonogenic with increased gene expression of the neuroectodermal markers NCAM1 and N-Cadherin, as well as Cyclins D1 and D2, compared to DNCs. All three cell populations expressed recognised mesenchymal stem cell surface markers (CD29, CD44, CD73, CD90), yet only CSPCs and CDCs showed multilineage differentiation potential. CDC populations expressed significantly higher levels of type 2 collagen and bone morphogenetic protein 2 genes, with greater cartilage extracellular matrix secretion. When DNCs were cultured in isolation, there was reduced chondrogenicity and higher expression of type 1 collagen, stromal cell-derived factor 1 (SDF-1), CD73 and CD90, recognised markers of a fibroblast-like phenotype.ConclusionsFibronectin-adherent CSPCs demonstrate a unique gene expression profile compared to non-fibronectin-adherent DNCs. DNCs cultured in isolation, without CSPCs, express fibroblastic phenotype with reduced chondrogenicity. Mixed populations of stem/progenitor cells and chondrocytes were required for optimal chondrogenesis, suggesting that CSPCs may be required to retain phenotypic stability and chondrogenic potential of DNCs. Crosstalk between DNCs and CSPCs is proposed based on SDF-1 signalling.
Highlights
The ability to successfully tissue engineer cartilage would have a significant impact on the ability to reconstruct cartilaginous defects and thereby restore function
Fibronectin-adherent Cartilage-derived stem/progenitor cell (CSPC) demonstrate a unique gene expression profile compared to non-fibronectinadherent Differentiated nasoseptal chondrocyte (DNC)
DNCs cultured in isolation, without CSPCs, express fibroblastic phenotype with reduced chondrogenicity
Summary
The ability to successfully tissue engineer cartilage would have a significant impact on the ability to reconstruct cartilaginous defects and thereby restore function. Contemporary cartilage tissue engineered implants, often using unrelated adult stem cell sources, do not produce stable, physiologically relevant cartilage [1, 2]. The use of stem cells in cartilage tissue engineering was a major development in the field. Mesenchymal stem cells (MSCs) from unrelated sources including the bone marrow, adipose tissue and skeletal muscle demonstrate chondrogenic potential, the majority of studies have shown that these MSCs often lead to fibrotic and calcified cartilage with poor mechanical properties and low physiological relevance [10, 13,14,15,16]. Since cartilage-derived stem/progenitor cells (CSPCs) were first identified in articular cartilage using differential adhesion to fibronectin, their self-renewal capacity and niche-specific lineage preference for chondrogenesis have propelled their application for cartilage tissue engineering. Our aim was to isolate and characterise nasoseptal CSPCs alongside nasoseptal chondrocyte populations and determine chondrogenic capacity
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call