Tendon Immune Regeneration: Insights on the Synergetic Role of Stem and Immune Cells during Tendon Regeneration
Valentina Russo,
Mohammad El Khatib,
Giuseppe Prencipe,
Maria Rita Citeroni,
Melisa Faydaver,
Annunziata Mauro,
Paolo Berardinelli,
Adrián Cerveró-Varona,
Arlette A. Haidar-Montes,
Maura Turriani,
Oriana Di Giacinto,
Marcello Raspa,
Ferdinando Scavizzi,
Fabrizio Bonaventura,
Johannes Stöckl,
Barbara Barboni
Affiliations
Valentina Russo
Unit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, Italy
Mohammad El Khatib
Unit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, Italy
Giuseppe Prencipe
Unit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, Italy
Maria Rita Citeroni
Unit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, Italy
Melisa Faydaver
Unit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, Italy
Annunziata Mauro
Unit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, Italy
Paolo Berardinelli
Unit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, Italy
Adrián Cerveró-Varona
Unit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, Italy
Arlette A. Haidar-Montes
Unit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, Italy
Maura Turriani
Unit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, Italy
Oriana Di Giacinto
Unit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, Italy
Marcello Raspa
National Research Council (CNR), Campus International Development (EMMA-INFRAFRONTIER-IMPC), Institute of Biochemistry and Cellular Biology (IBBC), 00015 Monterotondo Scalo, Italy
Ferdinando Scavizzi
National Research Council (CNR), Campus International Development (EMMA-INFRAFRONTIER-IMPC), Institute of Biochemistry and Cellular Biology (IBBC), 00015 Monterotondo Scalo, Italy
Fabrizio Bonaventura
National Research Council (CNR), Campus International Development (EMMA-INFRAFRONTIER-IMPC), Institute of Biochemistry and Cellular Biology (IBBC), 00015 Monterotondo Scalo, Italy
Johannes Stöckl
Centre for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Medical University of Vienna, 1090 Vienna, Austria
Barbara Barboni
Unit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, Italy
Tendon disorders represent a very common pathology in today’s population, and tendinopathies that account 30% of tendon-related injuries, affect yearly millions of people which in turn cause huge socioeconomic and health repercussions worldwide. Inflammation plays a prominent role in the development of tendon pathologies, and advances in understanding the underlying mechanisms during the inflammatory state have provided additional insights into its potential role in tendon disorders. Different cell compartments, in combination with secreted immune modulators, have shown to control and modulate the inflammatory response during tendinopathies. Stromal compartment represented by tenocytes has shown to display an important role in orchestrating the inflammatory response during tendon injuries due to the interplay they exhibit with the immune-sensing and infiltrating compartments, which belong to resident and recruited immune cells. The use of stem cells or their derived secretomes within the regenerative medicine field might represent synergic new therapeutical approaches that can be used to tune the reaction of immune cells within the damaged tissues. To this end, promising opportunities are headed to the stimulation of macrophages polarization towards anti-inflammatory phenotype together with the recruitment of stem cells, that possess immunomodulatory properties, able to infiltrate within the damaged tissues and improve tendinopathies resolution. Indeed, the comprehension of the interactions between tenocytes or stem cells with the immune cells might considerably modulate the immune reaction solving hence the inflammatory response and preventing fibrotic tissue formation. The purpose of this review is to compare the roles of distinct cell compartments during tendon homeostasis and injury. Furthermore, the role of immune cells in this field, as well as their interactions with stem cells and tenocytes during tendon regeneration, will be discussed to gain insights into new ways for dealing with tendinopathies.
