Search

Interstitial cells are present in the environment of stem cells in order to increase stem cell proliferation and differentiation and they are important to increase the efficiency of their transplantation. Telocytes (TCs) play an important role both in the preservation of tissue organ integrity and in the pathophysiology of many diseases, especially cancer. They make homo- or heterocellular contacts to form the structure of 3D network through their telopodes and deliver signaling molecules via a juxtacrine and/or paracrine association by budding shed vesicles into the vascular, nervous and endocrine systems. During this interaction, along with organelles, mRNA, microRNA, long non-coding RNA, and genomic DNA are transferred. This review article not only specifies the properties of TCs and their roles in the tissue organ microenvironment but also gives information about the factors that play a role in the transport of epigenetic information by TCs.

The placenta is the main organ that allows the fertilized oocyte to develop and mature. It allows the fetus to grow in the prenatal period by transferring oxygen and nutrients between the mother and the fetus. It acts as a basic endocrine organ which creates the physiological changes related to pregnancy and birth in the mother. Removal of wastes and carbon dioxide from the fetus is also achieved by the placenta. It prevents the rejection of the fetus and protects the fetus from harmful effects. Research on the human placenta focuses on understanding the placental structure and function to illuminate the complex structure of this important organ with technological advances. The structure and function of the placental barrier have been investigated with in vitro studies in 2D/3D, and various results have been published comparatively. In this review, we introduce the nature of the placenta with its 3D composition which has been called niche. Different cell types and placental structures are presented. We describe the systems and approaches used in the creation of current 3D placenta, placental transfer models as 3D placental barriers, and micro-engineered 3D placenta on-a-chip to explore complicated placental responses to nanoparticle exposure.

This study aims to evaluate the CD146+ stem cells obtained from the human umbilical cord and their extracellular matrix proteins on in vitro Pseudomonas aeruginosa and Staphylococcus aureus biofilms to understand their possible antimicrobial activity. CD146+ stem cells were determined according to cell surface markers and differentiation capacity. Characterization of the decellularized matrix was done with DAPI, Masson's Trichrome staining and proteome analysis. Cell viability/proliferation of cells in co-cultures was evaluated by WST-1 and crystal-violet staining. The effects of cells and decellularized matrix proteins on biofilms were investigated on a drip flow biofilm reactor and their effects on gene expression were determined by RT-qPCR. We observed that CD146/105+ stem cells could differentiate adipogenically and decellularized matrix showed negative DAPI and positive collagen staining with Masson' s Trichrome. Proteome analysis of the decellularized matrix revealed some matrix components and growth factors. Although the decellularized matrix significantly reduced the cell counts of P. aeruginosa, no significant difference was observed for S. aureus cells in both groups. Supporting data was obtained from the gene expression results of P. aeruginosa with the significant down-regulation of rhlR and lasR. For S. aureus, icaADBC genes were significantly up-regulated when grown on the decellularized matrix.

Stem cells are undifferentiated cells with self-renewal property and varying differentiation potential that allow the regeneration of tissue cells of an organism throughout adult life beginning from embryonic development. Through the asymmetric cell divisions, each stem cell replicates itself and produces an offspring identical with the mother cell, and a daughter cell that possesses the characteristics of a progenitor cell and commits to a specific lineage to differentiate into tissue cells to maintain homeostasis. To maintain a pool of stem cells to ensure tissue regeneration and homeostasis, it is important to regulate the metabolic functioning of stem cells, progenitor cells and adult tissue stem cells that will meet their internal and external needs. Upon fertilization, the zygote transforms metabolic reprogramming while implantation, embryonic development, organogenesis processes and after birth through adult life. Metabolism in stem cells is a concept that is relatively new to be enlightened. There are no adequate and comprehensive in vitro studies on the comparative analysis of the effects of one-carbon (1-C) metabolism on fetal and adult stem cells compared to embryonic and cancer stem cells’ studies that have been reported recently. Since 1-C metabolism is linking parental environmental/ dietary factors and fetal development, investigating the epigenetic, genetic, metabolic and developmental effects on adult period is necessary. Several mutations and abnormalities in 1-C metabolism have been noted in disease changing from diabetes, cancer, pregnancy-related outcomes such as pre-eclampsia, spontaneous abortion, placental abruption, premature delivery, and cardiovascular diseases. In this review, the effects of 1-C metabolism, mainly the methionine and folate metabolism, in stem cells that exist in different developmental stages will be discussed.

Small-diameter vascular grafts are needed for the treatment of coronary artery diseases in the case of limited accessibility of the autologous vessels. Synthetic scaffolds have many disadvantages so in recent years vascular constructs (VCs) made from cellularized natural scaffolds was seen to be very promising but number of studies comprising this area is very limited. In our study, our aim is to generate fully natural triple-layered VC that constitutes all the layers of blood vessel with vascular cells. CD146+ perivascular cells (PCs) were isolated from human umbilical cord vein (HUCV) and differentiated into smooth muscle cells (SMCs) and fibroblasts. They were then combined with collagen type I/elastin/dermatan sulfate and collagen type I/fibrin to form tunica media and tunica adventitia respectively. HUCV endothelial cells (ECs) were seeded on the construct by cell sheet engineering method after fibronectin and heparin coating. Characterization of the VC was performed by immunolabeling, histochemical staining and electron microscopy (SEM and TEM). Differentiated cells were identified by means of immunofluorescent (IF) labeling. SEM and TEM analysis of VCs revealed the presence of three histologic tunicae. Collagen and elastic fibers were observed within the ECM by histochemical staining. The vascular endothelial growth factor receptor expressing ECs in tunica intima; α-SMA expressing SMCs in tunica media and; the tenascin expressing fibroblasts in tunica adventitia were detected by IF labeling. In conclusion, by combining natural scaffolds and vascular cells differentiated from CD146+ PCs, VCs can be generated layer by layer. This study will provide a preliminary blood vessel model for generation of fully natural small-diameter vascular grafts.

Umbilical cord and cord blood are acceptable as attractive sources of mesenchymal and hematopoietic stem cells, since their collection is non-invasive, painless, and does not evoke the ethical concerns. Microorganism-stem cell interaction plays an important role in stem cell self-renewal, differentiation, secretion profile and death. In the literature, few researchers are examining the relationship between pathogenic and commensal bacteria with umbilical cord-derived Mesenchymal Stem Cells (MSCs). These relationships vary depending on the bacterial load and the presence of the immune cell in the environment. Several bacterial pathogens act in the regenerative capacity of MSCs by changing their phenotype, development and viability due to several stress factors that are created by a microorganism such as hypoxia, oxidative stress, etc. On the other hand, the anti-inflammatory and antibacterial effects of MSCs were shown and these phenomena increased when the number of bacteria was high but decreased in the presence of low amounts of bacteria. The antibacterial effects of MSCs increased in the early period of infection, while their effects were decreased in the late period with high inflammatory response and bacterial load. In this review, we discussed the microbial stresses on human umbilical cord stem cells.

Purpose: Transplantation of autologous and/or allogeneic blood vessels is the most convenient treatment for vascular diseases. With regard to extensive need for blood vessels, developments in vascu...

Skin is the main organ that covers the human body and acts as a protective barrier between the human body and the environment. Skin tissue as a stem cell source can be used for transplantation in therapeutic application in terms of its properties such as abundant, easy to access, high plasticity and high ability to regenerate. The immunological profile of these cells makes it a suitable resource for autologous and allogeneic applications. The lack of major histo-compatibility complex 1 is also advantageous in its use. Epidermal stem cells are the main stem cells in the skin and are suitable cells in tissue engineering studies for their important role in wound repair. In the last 30 years, many studies have been conducted to develop substitutions that mimic human skin. Stem cell-based skin substitutions have been developed to be used in clinical applications, to support the healing of acute and chronic wounds and as test systems for dermatological and pharmacological applications. In this chapter, tissue specific properties of epidermal stem cells, composition of their niche, regenerative approaches and repair of tissue degeneration have been examined.

Pericytes have crucial roles in blood-brain barrier function, blood vessel function/stability, angiogenesis, endothelial cell proliferation/differentiation, wound healing, and hematopoietic stem cells maintenance. They can be isolated from fetal and adult tissues and have multipotential differentiation capacity as mesenchymal stem cells (MSCs). All of these properties make pericytes as preferred cells in the field of tissue engineering. Current developments have shown that tissue-engineered three-dimensional (3D) systems including multiple cell layers (or types) and a supporting biological matrix represent the in vivo environment better than those monolayers on plastic dishes. Tissue-engineered models are also more ethical and cheaper systems than animal models. This chapter describes the role of pericytes in tissue engineering for regenerative medicine.

Perivascular cells are known to be ancestors of mesenchymal stem cells (MSCs) and can be obtained from heart, skin, bone marrow, eye, placenta and umbilical cord (UC). However detailed characterization of perivascular cells around the human UC vein and comparative analysis of them with MSCs haven't been done yet. In this study, our aim is to isolate perivascular cells from human UC vein and characterize them versus UC blood MSCs (UCB-MSCs). For this purpose, perivascular cells around the UC vein were isolated enzymatically and then purified with magnetic activated cell sorting (MACS) method using CD146 Microbead Kit respectively. MSCs were isolated from UCB by Ficoll density gradient solution. Perivascular cells and UCB-MSCs were characterized by osteogenic and adipogenic differentiation procedures, flow cytometric analysis [CD146, CD105, CD31, CD34, CD45 and alpha-smooth muscle actin (alpha-SMA)], and immunofluorescent staining (MAP1B and Tenascin C). Alizarin red and Oil red O staining results showed that perivascular cells and MSCs had osteogenic and adipogenic differentiation capacity. However, osteogenic differentiation capacity of perivascular cells were found to be less than UCB-MSCs. According to flow cytometric analysis, CD146 expression of perivascular cells were appeared to be 4.8-fold higher than UCB-MSCs. Expression of alpha-SMA, MAP1B and Tenascin-C from perivascular cells was determined by flow cytometry analysis and immunfluorescent staining. The results appear to support the fact that perivascular cells are the ancestors of MSCs in vascular area. They may be used as alternative cells to MSCs in the field of vascular tissue engineering.

Pericytes are CD146+ perivascular cells (PCs) that have multipotential differentiation capacity as mesenchymal stem cells. Beside their crucial roles in vascular development and blood flow regulation, they have ability to differentiate into vascular cell types in vivo. These properties make pericytes preferred cells in the field of vascular tissue engineering. Culture medium for in vitro differentiation of pericytes to vascular smooth muscle cells (SMCs) has not been defined yet. The aim of this study is to try different culture media for SMC differentiation of CD146+ PCs. For this purpose, CD146+ PCs were isolated from human umbilical cord vein. Then they were characterized by immunofluorescence staining and flow cytometric analysis. Three different culture media including; (1) Transforming growth factor beta 1 (TGF-beta 1)+ bone morphogenic protein 4, (2) TGF-beta 1+ l-ascorbic acid (l-AA) and (3) Horse serum, were compared for differentiation of CD146+ PCs to SMCs by IFS and real time polymerase chain reaction. As a result, in the case of SMC differentiation of CD146+ PCs, second culture medium including TGF-beta 1 and l-AA was found to be more effective than other two media. These results are important for establishing proper culture conditions for in vitro SMC differentiation of CD146+ PCs.

Mesenchymal stem cells (MSCs) are one of the most studied adult stem cells and in recent years. They have become attractive agents/cell source for cellular therapy and regenerative medicine applications. During investigations about their origin, researchers hypothesized that perivascular regions are the common anatomical regions where MSCs come from and perivascular cells like pericytes (PCs) (Rouget cells, mural cells) are in vivo counterparts of MSCs. Beside capillaries and microvessels as their most common locations, PCs are also found in large vessels (arteries and veins). They can be isolated from several tissues and organs particularly from retina and brain. There are different approaches about their isolation, characterization and culture but there has been no common protocol yet because of the lack of defined PC-specific marker. They make special contact with endothelial cells in the basement membrane and have very important functions in several tissues and organs. They participate in vascular development, stabilization, maturation, and remodeling, blood pressure control, endothelial cell proliferation and differentiation, contractility of vascular smooth muscle cells, wound healing, vasculogenesis and angiogenesis, long-term maintenance of hematopoietic stem cells in bone marrow niche. Their multipotential differentiation capacity and participation in many events in the body make PCs preferred cells in tissue engineering applications including 3D blood–brain barrier models, skeletal muscle constructs, bone tissue engineering and tissue-engineered vascular grafts.

Strategies to enhance the expansion of umbilical cord blood hematopoietic stem and progenitor cells (HSPCs) are crucial to enable their widespread application to adults and to overcome important limitations, such as delayed engraftment. Osteoblasts regulate HSPCs under steady-state and also under stress conditions, when HSPCs undergo numerous cycles of expansion. We hypothesized that osteoblasts could provide better stimulation for the expansion of multipotent HSPCs and subsequent hematopoietic recovery than mesenchymal stromal cells. Hence, we assessed the growth and engraftment modulatory activities of mesenchymal stromal cell-derived osteoblasts (M-OSTs) on hematopoietic progenitors. Mesenchymal stromal cells and M-OSTs favored the maintenance of CD34 + cells. The expansion of cord blood CD34 + cells and myeloid progenitors was highest in cultures supplemented with unfiltered M-OST-conditioned medium (M-OST CM). In addition, increased expression of cell surface receptors important for the homing of progenitors to the bone marrow, C-X-C chemokine receptor type 4 and lymphocyte function-associated antigen 1, was observed in CM-based cultures. Additionally, M-OST CM positively modulated the engraftment properties of expanded progenitors. Most notably, although human platelet levels remained steady in the first 2 weeks in mice transplanted with HSPCs expanded in standard medium, levels in mice transplanted with M-OST CM HSPCs rose continuously. Consistent with this, short-term human progenitor reconstitution was consistently greater in M-OST recipients. Finally, cytokine array-based profiling revealed increases in insulin-like growth factor binding protein 2, chemokines, and myeloid stimulating cytokines in M-OST CM. In conclusion, this study suggests that M-OSTs represent a new underappreciated source of feeder cells for the expansion of HSPCs with enhanced thrombopoietic activity.