Telocytes in regenerative medicine

Abstract

Telocytes (TCs) are a distinct type of interstitial cells characterized by a small cell body and extremely long and thin telopodes (Tps). The presence of TCs has been documented in many tissues and organs (go to http://www.telocytes.com). Functionally, TCs form a three-dimensional (3D) interstitial network by homocellular and heterocellular communication and are involved in the maintenance of tissue homeostasis. As important interstitial cells to guide or nurse putative stem and progenitor cells in stem cell niches in a spectrum of tissues and organs, TCs contribute to tissue repair and regeneration. This review focuses on the latest progresses regarding TCs in the repair and regeneration of different tissues and organs, including heart, lung, skeletal muscle, skin, meninges and choroid plexus, eye, liver, uterus and urinary system. By targeting TCs alone or in tandem with stem cells, we might promote regeneration and prevent the evolution to irreversible tissue damage. Exploring pharmacological or non-pharmacological methods to enhance the growth of TCs would be a novel therapeutic strategy besides exogenous transplantation for many diseased disorders.

Keywords: interstitial cells; progenitor cells; regeneration; regenerative medicine; stem cells; telocytes.

Figure 1

Representative electron microscopy image of a telocyte. A telocyte (TC) with at least three prolongations with several ‘beads’ along telopodes (Tps) is digitally coloured in blue. SMC: smooth muscle cell; N: Nuclei. Original magnification ×6800. Reproduced with permission from .

Figure 2

Three sequenced electron microscopy images of a telocyte. A telocyte (TC) with typical long and thin telopode (Tp) extending from the cell body; scale bars: 2 μm. Courtesy of Dr. LM. Popescu, Department of Ultrastructural Pathology, Victor Babeş National Institute of Pathology, Bucharest, Romania.

Figure 3

Three-dimensional (3D) reconstruction of a cardiac telocyte. (A and B) automated segmentation of a stack containing a telocyte (TC) with a long (20 ml), narrow (0.2-1 ml) and flat telepode (referred to Tp2 here). The right side of A shows X-Y-Z slice projections; scale bars: 2 ml. Reproduced with permission from .

Figure 4

Telocytes secrete extracellular vesicles. Telocytes (TCs) secrete exosomes (A), ectosomes (B), and multivesicular cargo (C). Tp: telopode; mvb: multivesicular bodies; m: mitochondria; er: endoplasmic reticulum; r: ribosome; scale bars: 0.5 μm. Reproduced with permission from .

Figure 5

Cardiac telocyte processes are in close contact with cardiac stem cells (CSC). Putative CSC in mouse CSC niche are shown in A and B. Committed cell (an intermediate stage between CSC and cardiomyocyte progenitors, CMP) is shown in C. TCp: telocyte processes; nu: nucleolus; ER: endoplasmic reticulum cisternae; m: mitochondria; n: nerve fibres; G: Golgi apparatus; v: vesicles; f: filaments. Reproduced with permission from .

Figure 6

Lung telocytes in stem cell niche. (A) Lung telocyte (TC) is in stem cell (SC) niche. Pn I: type I pneumocytes; Pn II: type II pneumocytes; vSMC: vascular smooth muscle cells. (B) One telopode (Tp1) is shown in contact with a Pn I and a SC. (C) One telopode (Tp2) is shown in contact with a Pn I. (D) A contact point (arrow) is found between a telopode (Tp1) and a Pn I. Scale bars: 2 μm (A); 1 μm (B–D). Reproduced with permission from .

Figure 7

A telocyte (TC) with its telopodes (Tps) around a progenitor cell in skeletal muscle. Tps are indicated with red arrows. mf: myofilaments; Gly: glycogen deposits; G: Golgi complex; N: nucleus; nc: nucleolus. Reproduced with permission from .

Figure 8

Telocytes bordering stem cells in dermal connective tissue. Telocytes (TCs) formed point contacts (arrows in A) and planar contacts (arrows in B) with stem cells in skin. bl: basal lamina; Tp: Telopode. Reproduced with permission from .

Figure 9

Telocytes bordering stem cells in eye. Telocytes (TCs) bordering stem cells in epithelial (A) and stromal (B and C) stem cell (SC) niches in mouse eye. bl: basal lamina; Tp: Telopode; Fb: fibroblast; n: nerve endings; L: lumen of an arteriole. Scale bars: 2 μm (A); 1 μm (B); 5 μm (C). Reproduced with permission from .