Current Stem Cell Research & Therapy - Volume 11, Issue 5, 2016

According to recent literature data, a peculiar connective tissue cell, called telocyte (TC), is present in almost all organs. Furthermore, TC subtypes, often coexisting in the same organ, but having different immunohistochemical and ultrastructural characteristics, have been demonstrated. Characteristically, TC, by connecting to each other and/or with other cell types, build three-dimensional networks. In the latter case they form a mixed network. TC, therefore, may be part of an integrated system to maintain tissue/organ function. Several roles have been proposed for the TC some of which support the importance of these cells in the differentiation and regenerative processes. Indeed, TC might behave as inductors/regulators of differentiation during morphogenesis due to their ability to release molecular signals and to construct the scaffold necessary for the parenchymal organization. In the adulthood, TC may be considered mesenchymal stromal cells able to differentiate in different cell types, such as the interstitial cells of Cajal, the resident myofibroblasts and the fibroblasts. Furthermore, the TC might be essential for the survival, proliferation, differentiation, maturation and guidance of the parenchymal stem cells located in the niches of several organs and, eventually, stimulate and sustain the regenerative processes.

Telocytes (TCs) are a distinct type of stromal cells with extremely thin and long prolongations called telopodes (Tps). TCs have been ubiquitously reported in almost all tissues and organs across species including heart. TCs are distinct from fibroblasts as evidenced by ultrastructural characteristics, immunohistochemistry features, gene profiles, proteome features, and miRNA signatures. By means of heterocellular junctions and extracellular vesicles, TCs may be able to regulate cardiac stem cells, angiogenesis, and anti-fibrosis. Therapeutic effects of cardiac TCs in myocardium infarction have been demonstrated. Cardiac TCs could be a source of cardiac repair and protection.

This review outlines the role of CD34+ stromal cells/telocytes (CD34+ SC/TCs) in repair and considers the following issues. Firstly, the conceptual aspects of repair, including regeneration and repair through granulation tissue (RTGT) as two types of repair, RTGT stages (inflammatory, proliferative, and remodeling), and tissue in repair as a substrate to assess the in vivo behavior of activated CD34+ SC/TCs. Subsequently, current knowledge of CD34+ SC/TCs, such as identification, characteristics, and functions, as well as possible stages (quiescent and activated) are taken into account. We then consider the role in regeneration of quiescent CD34+ SC/TCs (in unperturbed physiological conditions) as a nurse of stem cells (e.g., in the heart, skin, respiratory tree, gastrointestinal tract, liver, eye, and choroid plexus). Special attention is paid to the characteristics of activated CD34+ SC/TCs and the overlapping steps of activation with and without loss of CD34 expression and with and without gain of SMA expression. With this contribution, we establish the role of CD34+ SC/TCs as progenitor cells and as a source of fibroblasts and myofibroblasts in repair through granulation tissue, fibrosis, and tumor stroma. Activated CD34+ SC/TCs in encapsulation and other processes (e.g., Reinke’s edema, cutaneous myxoid cyst, mixomatous mitral valve degeneration, and fibrous papula of the face) are also outlined. Finally, similarities between modifications of CD34+ SC/TCs during in vivo activation and of multipotent mesenchymal stromal/stem cells in culture are examined in order to correlate the growing literature on CD34+ SC/TCs and the exponential research in cultured mesenchymal stromal/stem cells.

Telocytes (TCs), are a specific type of stromal cells, with a characteristic appearance including a small cell body and very long and thin telopodes. TCs have been reportedly identified in almost all human organs and tissues, including heart, pulmonary veins, and intestine. Cardiac TCs are widely distributed in the endocardium, epicardium, myocardium, and even stem cell niches. In physiological conditions, TCs form a three-dimensional architecture through homocellular and heterocellular interactions and stimulate the growth and differentiation of cardiac progenitor/stem cells during organogenesis. In pathological conditions, TCs improve cardiac function by contributing to cardiomyocyte renewal, enhancing angiogenesis, and decreasing cardiac fibrosis. Our understanding suggests these cells could lead to their use a source of cellular therapy to enhance repair of damaged myocardium. This review summarizes recent progress on the potential biological function of TCs in cardiac physiology and disease. Although TCs have beneficial effects towards cardiac injury, the molecular mechanisms whereby these effects are accomplished remain unclear. Additional in vivo functional studies on TCs will help improve our understanding of the mechanism by which TCs contribute to cardiac repair.

It was 50 years ago when the details of cellular structure were first observed with an electron microscope (EM). Today, transmission electron microscopy (TEM) still provides the highest resolution detail of cellular ultrastructure. The existence of telocytes (TCs) has been described by Hinescu and Popescu in 2005 and up to now, many studies have been done in different tissues. EM has been fundamental in identification and recognition of TC and relationship between TC and stem cells (SCs) in recent years. We present a review on the importance of TEM to provide major advances in the knowledge of the biology of these cells.

Telocytes (TCs) are a newly identified interstitial cell type which are named after and characterized by specialized thin, long synaptic structures called telopodes (Tps). The existence of TCs has been reported in lots of tissues and organs. There are numerous on-going studies to explore the biological functions of TCs, including their involvement in human disease. TCs are generally considered as supporting cells that help maintain the micro-structure of tissues by forming a three-dimensional interstitial network via intercellular junctions. In addition, TCs have also been implicated in the regulation of stem cell activity and the stem cell niche microenvironment, thus contributing to tissue repair and renewal. In this review, the most recent findings concerning hepatic TCs are described.

Telocytes (TC) are a new type of stromal cells initially found and studied in digestive and extra- digestive organs. These cells have a small cell body with 2 to 5 thin and extremely long cytoplasmic prolongations named telopodes. In recent years, TC have also been described in placental chorionic villi, located in a strategical position between the smooth muscle cells from fetal vessels and the myofibroblasts in the stromal villi. Unlike other organs, the placenta is not innervated and considering the strategic location of TC is has been postulated that TC function would be related to signal transduction mechanisms involved in the regulation of the fetal vessels blood flow, as well as in the shortening/lengthening of the chorionic villi, providing the necessary rhythmicity to the process of maternal/fetal metabolic exchange. Preeclampsia (PE) is a systemic syndrome that affects 4%–6% of pregnancies worldwide. It is characterized by a placental state of ischemia-hypoxia which triggers an oxidative stress stage with the concomitant production of reactive oxygen species (ROS) leading to an increase in the degree of placental apoptosis. Placental vascular tone is regulated by the vasodilator nitric oxide (NO) and, in PE cases, NO is diverted towards the formation of peroxynitrite, a powerful oxidative agent whose activity leads to an increase of placental apoptosis degree that compromises TC and myofibroblasts, a key feature we would like to emphasize in this work.

Cancer stem cells (CSCs) are considered to be the origin of cancer and it is suggested that they are resistant to chemotherapy. Current therapies fail to eradicate CSCs and therefore selecting a resistant cell subset that is able to facilitate tumor recurrences. Betulinic acid (BetA) is a broad acting natural compound, shown to induce cell death via the inhibition of the stearoyl-CoA- desaturase (SCD- 1). This enzyme converts saturated fatty acids into unsaturated fatty acids and is over-expressed in tumor cells. Here we show that BetA induces rapid cell death in all colon CSCs tested and is able to affect the CSCs directly as shown, via the loss of clonogenic capacity. Similar results were observed with inhibition of SCD-1, suggesting that SCD-1 activity is indeed a vulnerable link in colon CSCs and can be considered an ideal target for therapy in colon cancer.

The incidence of gastric cancer is third most prevalent among all malignant tumors in China. The conventional therapies for advanced gastric cancer are futile. Targeted gene therapy has become a promising alternative approach. Mesenchymal stem cells (MSCs) can be used as potential cellular vehicles for cancer therapy in vivo. This review will summarize the published data about the application of MSC-based targeted therapy for gastric cancer, and discuss some of the challenges associated with this method.

Colorectal cancer (CRC) is one of the most common cancers in the world. In recent decades, drug therapy and surgery have not achieved satisfactory results in curing CRC. The identification of cancer stem cells (CSCs) has provided a possible mechanistic explanation of CRC growth and metastasis. Traditional chemotherapy targets rapidly dividing cells, and since the CSCs can escape these therapies and become circulating cells, CSCs may be responsible for cancer relapse and metastasis. A better understanding of the roles of CSCs in the pathogenesis of primary CRC and its metastasis, as well as how these CSCs are regulated at the molecular level, is of paramount importance. In this review, we summarize the current understanding of the role of colorectal CSCs in CRC liver metastasis, and provide some insights on the potential implication of colorectal CSCs to better design therapeutic regimens and prevent CRC metastasis.

The development of induced pluripotent stem cell (iPSC) technology has inspired a series of methods to manipulate cell fate and has provided novel insight into the profound molecular events underlying the development of diseases. Reprogramming somatic cells into iPSCs has been intensively investigated. However, few studies have investigated the reprogramming of malignant cells and its potential application. Herein, we review the recent progress of iPSCs derived from malignant cells, and highlight tumor iPSCs applications on cancer research which mainly focus on mesenchymal-epithelial transition, genetic and epigenetic change, diseases model construction, drug screening and tumor pathway study.