Human Neonatal Thymus–Derived Mesenchymal Stromal Cells: Characterization, Differentiation, and Immunomodulatory Properties (original) (raw)
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Frontiers in Immunology, 2015
Mesenchymal stromal cells (MSC) have gained immense attraction in regenerative medicine, tissue engineering, and immunotherapy. This is based on their differentiation potential and the supply of pro-regenerative and immunomodulatory signals. MSC can be isolated from a multitude of tissue sources, but mainly bone marrow, adipose tissue, and birth-associated tissues (e.g., umbilical cord, cord blood, placenta) appear to be relevant for clinical translation in immune-mediated disorders. However, only a few studies directly compared the immunomodulatory potency of MSC from different tissue sources. This review compiles the current literature regarding the similarities and differences between these three sources for MSCs with a special focus on their immunomodulatory effects on T-lymphocyte subsets and monocytes, macrophages, and dendritic cells.
Human Thymus Mesenchymal Stromal Cells Augment Force Production in Self-Organized Cardiac Tissue
The Annals of Thoracic Surgery, 2010
Background-Mesenchymal stromal cells have been recently isolated from thymus gland tissue discarded after surgical procedures. The role of this novel cell type in heart regeneration has yet to be defined. The purpose of this study was to evaluate the therapeutic potential of human thymusderived mesenchymal stromal cells using self-organized cardiac tissue as an in vitro platform for quantitative assessment.
Mesenchymal stromal cells in the thymus
Inflammation and Regeneration
The microenvironment of the thymus is composed of a group of stromal cells that include endoderm-derived thymic epithelial cells (TECs) and mesenchymal stromal cells such as fibroblasts and serves as a site for the development of T cells. TECs are known to play an essential role in T cell differentiation and selection. Mesenchymal stromal cells have been less studied in terms of their immunological significance compared to TECs. Recently, new technologies have made it possible to identify and characterize mesenchymal stromal cells in the thymus, revealing their unique functions in thymic organogenesis and T cell development. This review outlines the current views on mesenchymal stromal cells in the thymus, particularly highlighting the newly discovered function of thymic fibroblasts in T cell repertoire selection.
Differentiation, 2010
Bone marrow mesenchymal stromal cells (BM-MSCs) with regenerative potential have been identified in heart. Whether these cells become new cardiac lineage cells by phenomena of transdifferentiation or fusion is also being investigated. Although, these mechanisms give cardiomyocytes, it has to be considered that MSCs transplantation could carry out ossification and calcification processes. An alternative might be the use of myocytes; however, the problem is the arrythmia. For those reasons, is that we investigated how to obtain cardiomyocyte-like cells from human MSCs (hMSCs). The aim of the present work was to evaluate a nuclear reprogramming of the hMSCs by a neonatal rat cardiomyocytes extract (EX) using Streptolysin O (SLO) treatment. hMSCs treated with 57.5 ng/ml SLO presented balllike, stick-like and myotube-like morphology. In the absence of cardiomyogenic stimuli, hMSCs expressed markers of cardiac phenotype-like sarcomeric a-actinin, connexin-43 and GATA-4. However, when hMSCs were treated with SLO +EX or 10 mM of 5-azacytidine (5-AZA), the expression of these markers were significantly increased and furthermore, expressed SERCA-2, cardiac Troponin I, b-MyHC, desmin, MLC-2a and MLC-2v thus showing the phenotype of mature cardiomyocytes. PCR analysis showed that cardiomyocyte-related genes, such as b1-adrenergic receptor (b1-AR), MLC-2a and cardiac Troponin T, were expressed after SLO + EX treatment like with 5-AZA. We concluded that the extract of neonatal rat cardiomyocytes could promote a nuclear modification of hMSCs to cardiomyogenic-like cells differentiation. Since the 5-AZA treatment appears to be genotoxic and taking into account the obtained results, the nuclear reprogramming by cell extract may be an approach leading to the identification of soluble factors that drives the reprogramming.
Potential therapeutic applications of mesenchymal stromal cells
Pathology, 2011
Mesenchymal stromal cells (MSCs) are a non-homogeneous population of plastic-adherent cells which were initially isolated from post-natal bone marrow. They have the capacity to differentiate to multiple mesodermal lineages including bone, cartilage and adipose tissue. In stringent culture conditions, MSCs can also be induced to differentiate into different cell types of endoderm and neuroectoderm lineages. To date, no specific marker identifies MSCs, although a number of cell surface antigens have been described which enrich for MSCs. Mesenchymal stromal cells possess a number of properties which have generated considerable interest in diverse cellular therapeutic applications. The capacity of MSCs to differentiate into multiple different cell lineages has seen them actively explored for tissue repair, particularly in cardiac, orthopaedic and neurological applications. A large body of data indicates that MSCs possess immunomodulatory properties. Mesenchymal stromal cells are immunosuppressive, interacting with T lymphocytes, antigen presenting cells, B lymphocytes, and natural killer cells. In addition, they are immunoprivileged, allowing transplantation across allogeneic barriers. These immunomodulatory properties have seen infusion of MSCs for the treatment of steroid refractory graft versus host disease, a life threatening complication of haemopoietic cell transplantation, with promising results. Furthermore, these immune functions may lead to roles in the facilitation of engraftment, induction of tolerance and as therapy in autoimmune disease.
Tissue-specific Differentiation Potency of Mesenchymal Stromal Cells from Perinatal Tissues
Scientific reports, 2016
Human perinatal tissue is an abundant source of mesenchymal stromal cells(MSCs) and lacks the ethical concerns. Perinatal MSCs can be obtained from various tissues as like amnion, chorion, and umbilical cord. Still, little is known of the distinct nature of each MSC type. In this study, we successfully isolated and cultured MSCs from amnion(AMSCs), chorion(CMSCs), and umbilical cord(UC-MSCs). Proliferation potential was different among them, that AMSCs revealed the lowest proliferation rate due to increased Annexin V and senescence-associated β-galactosidase positive cells. We demonstrated distinct characteristic gene expression according to the source of the original tissue using microarray. In particular, genes associated with apoptosis and senescence including CDKN2A were up-regulated in AMSCs. In CMSCs, genes associated with heart morphogenesis and blood circulation including HTR2B were up-regulated. Genes associated with neurological system processes including NPY were up-regul...
International Immunology, 2010
Mesenchymal stem or multipotent stromal cells (MSCs) have been implicated in tissue maintenance and repair and regulating immune effector cells through different mechanisms. These functions in mouse were primarily described for bone marrow (BM)-derived MSCs. To learn more about MSCs of different tissue origin, we compared the immunophenotype, differentiation ability to adipocyte and bone and immunomodulatory activity of MSCs isolated from BM, spleen, thymus and aorta wall of 14-day-old C57Bl/6 mice. The established cell lines fulfilled the requirements described for MSCs in terms of morphology, surface marker expression and differentiation potential although they were distinguishable regarding the expression pattern of the MSC markers and ability generating other cell types. Most importantly, a remarkable diversity was shown in the capacity of inhibition of mitogenand alloantigen-induced T-cell proliferation, since BM-and spleen-derived MSCs were the most powerful aorta-derived MSCs were less effective, whereas thymus-derived mesenchymal cells were unable to block T-cell growth in vitro. Accordingly, BM, spleen and aorta, but not thymus-derived MSCs, in combination with BM hematopoietic cells were equally efficient to prevent streptozotocininduced diabetes in vivo. These findings suggested that MSCs residing in different organs might stem from common ancestor; however, once populating into a given tissue microenvironment, they acquire specific properties mainly in the term of the immunoregulatory function.
Efficient expansion of mesenchymal stromal cells from umbilical cord under low serum conditions
Cytotherapy, 2009
Background aims Mesenchymal stromal cells (MSC) are of clinical interest for their potential use in regenerative medicine and immunotherapy. Originally derived from bone marrow (BM), MSC have now been isolated from most tissues, including umbilical cord (UC) and UC blood (UCB). If MSC from UC are biologically equivalent to those from BM, they would be attractive as a readily available and non-invasive source for cellular therapies. Methods Sections of UC were separated into vascular and Wharton's jelly (WJ) fractions, which were then digested individually to release MSC that were isolated by plastic adherence in a 10% fetal calf serum (FCS) medium, or a low serum medium designed for multipotent adult progenitor cells (MAPC). The resulting perivascular (PV) and WJ MSC lines were assayed for expression of characteristic markers and differentiation and immunosuppressive properties. Results MSC lines were readily derived from most UC tested. Cells grown in MAPC medium (MM) tended to be smaller and more elongated and expressed more nestin, but did not differ substantially in their growth rate, expression of other markers and differentiation capacity. All UC lines tested were adipogenic but poorly osteogenic, and were equivalent in their ability to suppress T-cell proliferation induced by phytohemagglutinin (PHA), activation beads and allostimulation. Conclusions UC is a convenient, effi cient source of MSC that can be expanded under low serum conditions for application on future studies of tissue regeneration and immunosuppression.
Comparative analysis of mesenchymal stromal cells from murine bone marrow and amniotic fluid
Cytotherapy, 2007
The main goal of this study was a comparison of biological properties of mesenchymal stromal cells (MSCs) obtained from bone marrow, adipose tissue and umbilical cord with respect to articular cartilage regeneration. MSCs were isolated and expanded in vitro up to the third passage. The kinetics of proliferation was analyzed by cell analyzer CEDEX XS and expression of selected markers was assessed by flow cytometry. The morphology was analyzed by inverted microscope and TEM. Pellet culture system and chondrogenic medium containing TGF-β1 was used to induce chondrogenic differentiation. Chondrogenesis was analyzed by real-time PCR; the expression of collagen type I and type II was compared. MSCs from all sources showed similar kinetics of proliferation and shared expression of CD73, CD90 and CD105; and were negative for CD14, CD20, CD34 and CD45. Observation under inverted microscope and TEM showed similar morphology of all analyzed MSCs. Cells from all sources underwent chondrogenic differentiation-they expressed collagen type II and acid mucopolysaccharides typical for hyaline cartilage. On the basis of obtained results it should be emphasized that MSCs from bone marrow, adipose tissue and umbilical cord share biological properties. They possess the chondrogenic potential and may be utilized in cartilage tissue engineering.
Cardiomyocyte differentiation of perinatally‑derived mesenchymal stem cells
Molecular medicine reports, 2013
Coronary heart disease is major cause of mortality worldwide and several risk factors have been shown to play a role in its pathogenesis, including smoking, obesity, hypertension and hypercholesterolemia. A number of therapeutic methods have been developed to improve the quality of patients' lives, including stem cell therapy using mesenchymal stem cells (MSCs). Perinatal sources, including the placenta (PL) and umbilical cord (UC), are rich sources of MSCs and have been identified as a potential source of cells for therapeutic use. Their role in cardiogenic differentiation is also of contemporary medical interest. The present study demonstrated the induced differentiation of MSCs obtained from the UC, PL and Wharton's jelly (WJ) into cardiomyocytes, using 10 µM 5‑azacytidine. The characteristics of the MSCs from each source were studied and their morphology was compared. An immunofluorescence analysis for the cardiac‑specific markers, GATA4 and Troponin T (TnT), was perform...