Cross-Talk Between Human Tenocytes and Bone Marrow Stromal Cells Potentiates Extracellular Matrix Remodeling In Vitro

ABSTRACT Tendon and ligament (T/L) pathologies account for a significant portion of musculoskeletal injuries and disorders. Tissue engineering has emerged as a promising solution in the regeneration of both tissues. Specifically, the use of multipotent human mesenchymal stromal cells (hMSC) has show...

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Bibliographic Details
Published in:Journal of cellular biochemistry 2016-03, Vol.117 (3), p.684-693
Main Authors: Ekwueme, Emmanuel C., Shah, Jay V., Mohiuddin, Mahir, Ghebes, Corina A., Crispim, João F., Saris, Daniël B.F., Fernandes, Hugo A.M., Freeman, Joseph W.
Format: Article
Language:English
Subjects:
Cell Communication
Cell Shape
Cells, Cultured
CO-CULTURE
Coculture Techniques
Collagen - metabolism
Extracellular Matrix - metabolism
Extracellular Matrix Proteins - genetics
Extracellular Matrix Proteins - metabolism
Gene Expression
Humans
LIGAMENT
MESENCHYMAL STROMAL CELLS
Mesenchymal Stromal Cells - physiology
PARACRINE SIGNALING
Regenerative Medicine
TENDON
Tendons - cytology
Tendons - metabolism
Tissue Engineering
TRANSFORMING GROWTH FACTOR BETA
Transforming Growth Factor beta1 - metabolism
Transforming Growth Factor beta1 - secretion
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Summary:ABSTRACT Tendon and ligament (T/L) pathologies account for a significant portion of musculoskeletal injuries and disorders. Tissue engineering has emerged as a promising solution in the regeneration of both tissues. Specifically, the use of multipotent human mesenchymal stromal cells (hMSC) has shown great promise to serve as both a suitable cell source for tenogenic regeneration and a source of trophic factors to induce tenogenesis. Using four donor sets, we investigated the bidirectional paracrine tenogenic response between human hamstring tenocytes (hHT) and bone marrow‐derived hMSC. Cell metabolic assays showed that only one hHT donor experienced sustained notable increases in cell metabolic activity during co‐culture. Histological staining confirmed that co‐culture induced elevated collagen protein levels in both cell types at varying time‐points in two of four donor sets assessed. Gene expression analysis using qPCR showed the varied up‐regulation of anabolic and catabolic markers involved in extracellular matrix maintenance for hMSC and hHT. Furthermore, analysis of hMSC/hHT co‐culture secretome using a reporter cell line for TGF‐β, a potent inducer of tenogenesis, revealed a trend of higher TGF‐β bioactivity in hMSC secretome compared to hHT. Finally, hHT cytoskeletal immunostaining confirmed that both cell types released soluble factors capable of inducing favorable tenogenic morphology, comparable to control levels of soluble TGF‐β1. These results suggest a potential for TGF‐β‐mediated signaling mechanism that is involved during the paracrine interplay between the two cell types that is reminiscent of T/L matrix remodeling/turnover. These findings have significant implications in the clinical use of hMSC for common T/L pathologies. J. Cell. Biochem. 117: 684–693, 2016. © 2015 Wiley Periodicals, Inc.
ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.25353