Fibrin Scaffolds Perfused with Transforming Growth Factor-β1 as an In Vitro Model to Study Healthy and Tendinopathic Human Tendon Stem/Progenitor Cells

Author:

Ciardulli Maria Camilla1,Lovecchio Joseph23ORCID,Parolini Ornella45ORCID,Giordano Emanuele67ORCID,Maffulli Nicola8,Della Porta Giovanna19ORCID

Affiliation:

1. Translational Nanomedicine Laboratory, Department of Medicine, Surgery and Dentistry, University of Salerno, Via S. Allende 43, 84081 Baronissi, Italy

2. School of Science and Engineering, Reykjavík University, 102 Reykjavík, Iceland

3. Institute of Biomedical and Neural Engineering, Reykjavik University, 102 Reykjavík, Iceland

4. Department of Life Science and Public Health, Università Cattolica del Sacro Cuore, 00168 Rome, Italy

5. Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Università Cattolica del Sacro Cuore, 00136 Rome, Italy

6. Laboratory of Cellular and Molecular Engineering “Silvio Cavalcanti”, Department of Electrical, Electronic and Information Engineering “Guglielmo Marconi” (DEI), University of Bologna, 47522 Cesena, Italy

7. Advanced Research Center on Electronic Systems (ARCES), University of Bologna, 40126 Bologna, Italy

8. Department of Trauma and Orthopaedics, Faculty of Medicine and Psychology, Sant’ Andrea Hospital, Sapienza University, 00189 Rome, Italy

9. Interdepartment Centre BIONAM, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy

Abstract

A limited understanding of tendon cell biology in healthy and pathological conditions has impeded the development of effective treatments, necessitating in vitro biomimetic models for studying tendon events. We established a dynamic culture using fibrin scaffolds, bioengineered with tendon stem/progenitor cells (hTSPCs) from healthy or diseased human biopsies and perfused with 20 ng/mL of human transforming growth factor-β1 for 21 days. Both cell types showed long-term viability and upregulated Scleraxis (SCX-A) and Tenomodulin (TNMD) gene expressions, indicating tenogenic activity. However, diseased hTSPCs underexpressed collagen type I and III (COL1A1 and COL3A1) genes and exhibited lower SCX-A and TNMD protein levels, but increased type I collagen production, with a type I/type III collagen ratio > 1.5 by day 14, matching healthy cells. Diseased hTSPCs also showed constant high levels of pro-inflammatory cytokines, such as IL-8 and IL-6. This biomimetic environment is a valuable tool for studying tenogenic and inflammatory events in healthy and diseased tendon cells and identifying new therapeutic targets.

Publisher

MDPI AG

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