Biomarkers for tissue engineering of the tendon-bone interface

Abstract

The tendon-bone interface (enthesis) is a highly sophisticated biomaterial junction that allows stress transfer between mechanically dissimilar materials. The enthesis encounters very high mechanical demands and the regenerative capacity is very low resulting in high rupture recurrence rates after surgery. Tissue engineering offers the potential to recover the functional integrity of entheses. However, recent enthesis tissue engineering approaches have been limited by the lack of knowledge about the cells present at this interface. Here we investigated the cellular differentiation of enthesis cells and compared the cellular pattern of enthesis cells to tendon and cartilage cells in a next generation sequencing transcriptome study. We integrated the transcriptome data with proteome data of a previous study to identify biomarkers of enthesis cell differentiation. Transcriptomics detected 34468 transcripts in total in enthesis, tendon, and cartilage. Transcriptome comparisons revealed 3980 differentially regulated candidates for enthesis and tendon, 395 for enthesis and cartilage, and 946 for cartilage and tendon. An asymmetric distribution of enriched genes was observed in enthesis and cartilage transcriptome comparison suggesting that enthesis cells are more chondrocyte-like than tenocyte-like. Integrative analysis of transcriptome and proteome data identified ten enthesis biomarkers and six tendon biomarkers. The observed gene expression characteristics and differentiation markers shed light into the nature of the cells present at the enthesis. The presented markers will foster enthesis tissue engineering approaches by setting a bench-mark for differentiation of seeded cells towards a physiologically relevant phenotype.

Enthesis Tissue Engineering: Biological Requirements Meet at the Interface

“…Together, these results support the hypothesis that the direct crosstalk between differentiated and stem cells within the system can potentiate fibrochondrogenic commitment characteristic of the chondrocyte-like phenotype observed for native enthesis cells [15]. Furthermore, conditioned media from parallel cultures of fibroblastsonly, osteoblasts-only, and fibroblast-osteoblast co-culture were collected and added to monocultures of BMSCs to evaluate the effect of paracrine communication [66].…”

“…A direct co-culture model with hTDCs and pre-OBs (1:1 cell ratio) was then established. [15,16] and the use of an optimal culture condition that can maintain different phenotypes at the same time is a major advantage supporting the combination of stem cells with differentiated cells.…”

Tissue Engineering for the Insertions of Tendons and Ligaments: An Overview of Electrospun Biomaterials and Structures

“…Cells are depicted cyan (scale bar = 150 μm). Image adapted from Kuntz et al (2018) (reproduced with permission under the terms of the CC BY 4.0 license. Copyright 2018, PLOS Publishing).…”

Biomimetic strategies for tendon/ligament-to-bone interface regeneration

“…2 C) [ 18 , 25 ]. Recently, Kuntz et al presented a transcriptomic study at the tendon-to-bone interface and identified several interface biomarkers by combining transcriptomics with proteomics, which provides a bench-mark to study whether the differentiation of seeded MSCs towards a physiological phenotype [ 29 ]. However, the precise identification of the cell subpopulations at the interface remains unknown.…”