Review
The potential role of telocytes in Tissue Engineering and Regenerative Medicine

https://doi.org/10.1016/j.semcdb.2016.01.021Get rights and content

Abstract

Research and ideas for potential applications in the field of Tissue Engineering (TE) and Regenerative Medicine (RM) have been constantly increasing over recent years, basically driven by the fundamental human dream of repairing and regenerating lost tissue and organ functions. The basic idea of TE is to combine cells with putative stem cell properties with extracellular matrix components, growth factors and supporting matrices to achieve independently growing tissue. As a side effect, in the past years, more insights have been gained into cell–cell interaction and how to manipulate cell behavior. However, to date the ideal cell source has still to be found. Apart from commonly known various stem cell sources, telocytes (TC) have recently attracted increasing attention because they might play a potential role for TE and RM. It becomes increasingly evident that TC provide a regenerative potential and act in cellular communication through their network-forming telopodes. While TE in vitro experiments can be the first step, the key for elucidating their regenerative role will be the investigation of the interaction of TC with the surrounding tissue. For later clinical applications further steps have to include an upscaling process of vascularization of engineered tissue. Arteriovenous loop models to vascularize such constructs provide an ideal platform for preclinical testing of future therapeutic concepts in RM. The following review article should give an overview of what is known so far about the potential role of TC in TE and RM.

Section snippets

Tissue Engineering and Regenerative Medicine

Regenerative Medicine (RM) is an interdisciplinary field of research and clinical application focused on the repair, replacement or regeneration of cells, tissues or organs to restore impaired function resulting from any cause, including congenital defects, disease, trauma and aging [1]. It uses a combination of several technological approaches that transforms it beyond traditional transplantation and replacement therapies. These approaches may include the use of soluble molecules, stem and

Basic Tissue Engineering concepts and techniques

Tissue Engineering may well be regarded as a truly interdisciplinary field that aims to overcome disadvantages of existing therapeutic concepts, by developing strategies for tissue replacement based on the combination of scaffolds, cells and growth factors. It therefore definitely represents an important research field due to the great demand for optimization of treatment strategies of tissue defects and the limited current treatment options for many diseases [8], [9] (Fig. 1).

Basically TE

New cell types for TE and RM: from Cajal-like cells to telocytes

Finally being described in 2010, telocytes (TC) were previously mentioned using the acronym ICLC (interstitial Cajal-like cells) [26]. However, TCs are not Cajal-like cells. They are different from the well-known Cajal cells of the intestine and considered as completely distinct in ultrastructure, immunophenotype, electrophysiology, gene profile and proteomics [26].

S. Ramon y Cajal discovered these cells more than 100 years ago in the muscle layer of the gut and called them “interstitial

Telocytes in various organs in TE and RM for clinical applications?

TC have to date been described in a broad range of tissues and organs. In the following section, we would like to point out some important findings and refer to the growing number of publications and reviews on TC to identify possible targets for RM. Often TC are described as assisting in the repair and restoration of tissue and organ function.

Telocytes and stem cells

Because regenerative potential is limited in humans, stem cell-based therapy remains a future hope for regeneration. To date, a broad range of methods and cells (embryonic stem cells; induced pluripotent stem cells; hematopoietic stem cells; multipotent mesenchymal stromal cells derived from blood, bone marrow, umbilical cord, and adipose tissue, etc.) (Fig. 6) have been investigated, but we are still waiting for the breakthrough in RM. There are recent publications indicating that TC and stem

Potential role of telocytes in Regenerative Medicine

Besides the use of an optimal tissue replacement matrix, cells are an integral part of Tissue Engineering approaches. Over the past few years, many cell populations have proved particularly promising for Tissue Engineering: MSC are multipotent undifferentiated cells that are located in various tissues of the body and maintain their differentiation potential during their entire lifespan. MSC are more frequently used in Tissue Engineering than tissue-specific cells due to the simple harvest and

Conclusions

According to the current literature and the huge number of hints of the regenerative potential of TC, at present there are great expectations for these cells by the Tissue Engineering and Regenerative Medicine community. Under the light of recent achievements of research in Regenerative Medicine, one might return to the myth of Prometheus and philosophize that not only the liver may carry the ability to renew, but also other vital organs like the heart. It is possible that further molecular and

Conflict of interest

All the authors confirm that there are no conflicts of interests with regard to this paper.

Acknowledgements

Our experimental studies are funded by the Staedtler Foundation, University of Erlangen-Nürnberg; the Office for Gender and Diversity, University of Erlangen-Nürnberg; the Forschungsstiftung Medizin Erlangen, University of Erlangen-Nürnberg, Erlangen, Germany; the Novartis Foundation; the Else Kröner-Fresenius Stiftung; the Baxter Innovations GmbH, Vienna, Austria, Dr. Fritz-Erler Fonds and the Xue Hong and Hans Georg Geis Foundation.

We would like to thank Prof. Sanda Cretoiu and Prof.

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      These synapses occurred not only in the human breast [28] but also in the interstitial tissue of various organs [48]. Although, TCs are cells that capable of acting as integrators of many intercellular functions there is a long way ahead to elucidate their functional capabilities [38,39,43]. In conclusion, our study provides evidence for the presence of TCs in all stages of the gland; not only in the resting stage as proved by other studies, but with immune-labeling differences suggesting different structural and physiological roles of TCs according to the stage requirements.

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      Several functions have been proposed for TCs, including tissue structural support, homeostasis maintenance, intercellular signaling, cell differentiation, immune surveillance, stem/progenitor cell guiding and nursing (Bei et al., 2015; Díaz-Flores et al., 2016; El Maadawi, 2016; Marini et al., 2017a). In addition, TCs seem to be involved in a variety of pathologies and participate in tissue regeneration, making these cells particularly attractive in the field of regenerative medicine (Popescu et al., 2011; Bei et al., 2015; Boos et al., 2016; Díaz-Flores et al., 2016; El Maadawi, 2016; Ibba-Manneschi et al., 2016; Mirancea, 2016; Marini et al., 2017a). It has also been suggested an involvement of TCs in contractility mechanisms and intercellular electrical communication of excitable tissues (Edelstein and Smythies, 2014; Bei et al., 2015; Díaz-Flores et al., 2016).

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