Mesenchymal Stem Cells Of Different Origin Research Articles

Proliferation-Related Features of the Human Mesenchymal Stem Cells Derived from Palatine Tonsils, Adipose Tissues, and Bone Marrow.

Mesenchymal stem cells (MSCs) are widely used in regenerative medicine and cell-based transplantations. However, an in-depth comparison of the different MSC origins is lacking. This study aimed to compare the expression of adipose-derived (AMSCs), bone marrow-derived (BMSCs), and tonsil-derived (TMSCs) and evaluate whether TMSCs are good alternatives for AMSCs or BMSCs. We analyzed the expression levels of 47,000 transcripts in AMSCs (n = 4), BMSCs (n = 4), and TMSCs (n = 4) using GeneChip. Microarray data were analyzed using the LIMMA package to compare the TMSCs, AMSCs, and BMSCs. Hub genes were analyzed using STRING and Cytoscape. To ascertain the functional roles of AURKA and AURKB, small interfering RNA (siRNA) molecules specifically targeting AURKA and AURKB mRNA were synthesized and employed to induce knockdown of AURKA and AURKB in TMSC and AMSC. We analyzed the expression level of OCT4, SOX-2, and NANOG genes in TMSC and AMSCs by cell culture and real-time PCR. We identified commonly increased 256 and decreased 160 genes in TMSCs from the differentially expressed genes (DEGs) between the TMSCs, AMSCs, and BMSCs. In the DEG-based protein-protein interaction and gene set enrichment analysis, hub genes (AURKA, AURKB, CDC20, and BUB1) highly expressed in TMSCs were enriched for development- and progression-related oocyte meiosis, the cell cycle, and ubiquitin-mediated proteolysis. In vitro analysis demonstrated that cells with downregulated expression of AURKA and AURKB exhibited a significant reduction in proliferation compared to control cells. However, silencing of the genes did not affect the differentiation capacity in TMSCs and AMSCs. Our study compared MSCs of different origins to better understand the similarities and differences among these cell types.

Mesenchymal stem cell application for treatment of neuroinflammation-induced cognitive impairment in mice.

Background: The present research has been undertaken to study the therapeutic potential of mesenchymal stem cells (MSCs) for the treatment of neuroinflammation-induced cognitive disorders. Methods: Either umbilical cord or adipose MSCs were injected into mice treated with lipopolysaccharide. The mice were studied in behavioral tests, and their brains were examined by means of immunohistochemistry, electron microscopy and sandwich ELISA. Results: MSCs, introduced either intravenously or intraperitoneally, restored episodic memory of mice disturbed by inflammation, normalized nAChR and Aβ1-42 levels and stimulated proliferation of neural progenitor cells in the brain. The effect of MSCs was observed for months, whereas that of MSC-conditioned medium was transient and stimulated an immune reaction. SDF-1α potentiated the effects of MSCs on the brain and memory. Conclusion: MSCs of different origins provide a long-term therapeutic effect in the treatment of neuroinflammation-induced episodic memory impairment.

Flow cytometric characterization of cell surface markers to differentiate between fibroblasts and mesenchymal stem cells of different origin.

Identification and purification of mesenchymal stem cells (MSCs) expanded in culture for therapeutic use is crucial for improved yield and optimal results. Fibroblasts are the most common cell type in connective tissue and are commonly found as contaminants of MSC cultures, affecting cell yield and potentially causing tumour formation after cell transplantation. In the current study, we wished to identify cell surface markers that can differentiate MSCs of different origins from fibroblasts. Mesenchymal stem cells were isolated from bone marrow, adipose tissue, Wharton's jelly, and placental tissue, and fibroblasts were isolated from foreskin (as a negative control) in order to examine the differences in the expression of a panel of 14 different cell surface markers using multiplex flow cytometry. Our results indicate that the following markers could be useful in differentiating between fibroblasts and MSCs derived from the following: adipose tissue - CD79a, CD105, CD106, CD146, and CD271; Wharton's jelly - CD14, CD56, and CD105; bone marrow - CD105, CD106, and CD146; and placental tissue - CD14, CD105, and CD146. Furthermore, we found that, contradictory to previous studies, CD26 is not fibroblast specific. The results of our study indicate that cell surface markers may prove to be a useful tool in the discrimination between MSCs of different origins and fibroblasts, and thus may be used to authenticate the identity of the isolated cells.

Osteogenic and chondrogenic differentiation potential of mesenchymal stem cells obtained from the bone marrow and placenta

Mesenchymal stem cells (MSC) represent a perspective resource for cell biotechnology. However the question of chondrogenic and osteogenic capacity of MSC of different origin remains under study.The aim of this study was to analyze the osteo-chondrogenic differentiation potential of MSC obtained from the bone marrow and placenta. The results of our studies have indicated that bone marrow-derived and placenta-derived MSC showed a chondrogenic potential in vitro after a chondrogenic induction with specific differentiation media. But for bone marrowderived MSC, the chondrogenic program was realized by expression of collagens (Coll2, Coll10), while in placenta-derived MSC cultures we found a progressive increase in COMP and Ver expression, so bone marrow-derived MSC is more preferable for use in cartilage tissue engineering. Regarding the results on alkaline phosphatase and alizarin red staining, bone marrowderived MSC showed a more significant osteogenic potential compared to placenta-derived MSC. Bone marrow-derived MSC in the composition of fibrin gel after osteogenic induction on the 14th day exhibited the activity of alkaline phosphatase, calcium depositions inside the cells and extracellular matrix, the increase in Sp7 and DMP expression.

Mesenchymal stem cells inhibit the growth of prostate carcinoma cells in a long-term cultivation

Mesenchymal stem cells (MSCs) migrate to sites of inflammation and tumor formation in the body. In this way, MSCs become activated and release a plethora of growth factors and cytokines that are involved in the regulation and remodeling of the tumor microenvironment. The effect of MSCs on tumor cells is bipolar by nature and the data on this interaction is quite contradictory. The purpose of this work is to investigate the interaction between MSCs of different origin (bone marrow, adipose tissue) and PC-3 tumor cell line derived from prostate cancer in a long-term (9 days) cultivation. Our study assessed the proliferation, vitality and apoptosis of PC-3 tumor cells exposed to MSCs’ contact and products. As a result, we observed a significant growth inhibitory effect on PC-3 cells due to cell-to-cell contact with MSCs. Furthermore, tumor cells also showed contact-mediated increase in apoptosis levels. In addition, bone marrow-derived MSCs had a stronger effect on the PC-3 cell line compared to adipose tissue-derived MSCs.

Comparison of the Biological Characteristics of Mesenchymal Stem Cells Derived from Bone Marrow and Skin.

Mesenchymal stem cells (MSCs) exhibit high proliferation and self-renewal capabilities and are critical for tissue repair and regeneration during ontogenesis. They also play a role in immunomodulation. MSCs can be isolated from a variety of tissues and have many potential applications in the clinical setting. However, MSCs of different origins may possess different biological characteristics. In this study, we performed a comprehensive comparison of MSCs isolated from bone marrow and skin (BMMSCs and SMSCs, resp.), including analysis of the skin sampling area, separation method, culture conditions, primary and passage culture times, cell surface markers, multipotency, cytokine secretion, gene expression, and fibroblast-like features. The results showed that the MSCs from both sources had similar cell morphologies, surface markers, and differentiation capacities. However, the two cell types exhibited major differences in growth characteristics; the primary culture time of BMMSCs was significantly shorter than that of SMSCs, whereas the growth rate of BMMSCs was lower than that of SMSCs after passaging. Moreover, differences in gene expression and cytokine secretion profiles were observed. For example, secretion of proliferative cytokines was significantly higher for SMSCs than for BMMSCs. Our findings provide insights into the different biological functions of both cell types.

COMPARISON OF PROLIFERATION AND IMMUNOPHENOTYPE OF MSC, OBTAINEDFROM BONE MARROW, ADIPOSE TISSUE AND UMBILICAL CORD

Mesenchymal stem cells (MSC) can be applied for treatment of different diseases. Human MSC have been isolated from bone marrow, adipose tissue, umbilical cord blood. umbilical cord MSCs (uC- MSC) are obtained during birth with non-invasive, non-traumatic methods and thus seem a good candidate for clinical practice instead of bone-marrow MSC (BM-MSC). It is yet unknown wheth- er the immunophenotype and proliferation capacity of uC-MSC are similar to adipose-derived stem cells (AdSCs) or BM-MSC. The goal of this research was to study the immunophenotype and prolifer- atiion capacity of uC-MSC, AdSCs and BM-MSC. The results indicated that MSC of different origin had similar morphological and immunophenotypic characteristics with minor differences. uC-MSC differed from other cultures by constant level of Cd105 expression, the presence of minor Cd10 - and Cd13 - populations and higher proliferative activity. BM-MSC were characterized by reduced expres- sion levels of Cd90, compared with the uC-MSCs and AdSCs. These data confirm the similarity of uC-MSC with BM-MSCs and AdSCs and the possibility of their use in clinical practice instead of hard-to-obtain BM-MSC.

Stem cell therapy in the management of shoulder rotator cuff disorders.

Rotator cuff tears are frequent shoulder problems that are usually dealt with surgical repair. Despite improved surgical techniques, the tendon-to-bone healing rate is unsatisfactory due to difficulties in restoring the delicate transitional tissue between bone and tendon. It is essential to understand the molecular mechanisms that determine this failure. The study of the molecular environment during embryogenesis and during normal healing after injury is key in devising strategies to get a successful repair. Mesenchymal stem cells (MSC) can differentiate into different mesodermal tissues and have a strong paracrine, anti-inflammatory, immunoregulatory and angiogenic potential. Stem cell therapy is thus a potentially effective therapy to enhance rotator cuff healing. Promising results have been reported with the use of autologous MSC of different origins in animal studies: they have shown to have better healing properties, increasing the amount of fibrocartilage formation and improving the orientation of fibrocartilage fibers with less immunologic response and reduced lymphocyte infiltration. All these changes lead to an increase in biomechanical strength. However, animal research is still inconclusive and more experimental studies are needed before human application. Future directions include expanded stem cell therapy in combination with growth factors or different scaffolds as well as new stem cell types and gene therapy.

MRNAs and miRNAs profiling of mesenchymal stem cells derived from amniotic fluid and skin: the double face of the coin

Mesenchymal stem cells (MSCs) can be isolated from different adult sources and, even if the minimal criteria for defining MSCs have been reported, the scientific question about the potential distinctions among MSCs derived from different sources is still open. In particular, it is debated whether MSCs of different origin have the same grade of stemness or whether the source affects their undifferentiated status. Here, we report not only the isolation and the traditional characterization of MSCs derived from amniotic fluid (AF-MSCs) and skin (S-MSCs) but also a molecular characterization based on mRNAs and miRNAs profiling. Our results show that, even if both AF- and S-MSCs are mostly regulated by the same pathways (such as Wnt, MAPK and TGF-β), there are some important differences at the molecular level that directly affect important cellular features, such as the ability to differentiate into adipocytes. In conclusion, even if further studies are necessary to improve the knowledge about the role of each dysregulated miRNAs gene, these differences may actually strengthen the question about the importance of tissue origin.

The immunomodulatory activity of human mesenchymal stem cells is related to different tissue origin

Event Abstract Back to Event The immunomodulatory activity of human mesenchymal stem cells is related to different tissue origin Drenka Trivanović1*, Vesna Ilić1, Jelena Kocić1, Aleksandra Krstić1, Slavko Mojsilović1, Ivana Okić-Djordjević1, Juan Francisco Santibanez1, Diana Bugarski1 and Gordana Jovčić1 1 Institute for Medical Research, University of Belgrade, Serbia Mesenchymal stem cells (MSCs) exert potent immunomodulatory capacity that makes them attractive as cellular therapeutic agents. In this study we compared the capability of MSCs derived from four different adult tissues: umbilical cord Wharton’s Jelly (UC-MSCs), peripheral blood (PB-MSCs), adipose tissue (AT-MSCs) and dental pulp (DP-MSCs) to modulate the allogene and mitogen stimulated proliferation of healthy donor PBMCs. The constitutive, as well as the mRNA expression of immunomodulatory molecules and factors after cultivation with PBMCs or with IFN-γ and TNF-α was also analysed. All four MSCs types inhibited the proliferation of mitogen-stimulated PBMCs. As a third part of MLR, AT-MSCs, PB-MSCs and UC-MSCs exhibited inhibitory, while DP-MSCs had stimulatory effect on MLR. Only AT-MSC functioned as alloantigen presenting cells. Direct contact with PBMCs increased the expression of IL-6, TGF-β, Cox2, IDO-1, HLA-G5 and particularly HLA-DR in all four MSCs types. Pre-treatment with proinflammatory cytokines, with more evident effect of TNF-α, upregulated the expression of IL-6, TGF-β and Cox2 in AT-MSCs and DP-MSCs, and increased constitutive expression of IDO-1 and HLA-DR in AT-MSCs. As for UC-MSCs and PB-MSCs, the constitutive expression of HLA-DR, IL-6, TGF-β, Cox2, IDO-1, HLA-G5 was not detected, neither was induced by the proinflammatory cytokines. The results demonstrated that MSCs of different origin might exhibit different immunomodulatory capacities, accompanied with different expression of immunogenic molecules and regulatory molecules, which are differentially regulated by both interactions between MSCs with their target cells, as well as by the pro-inflammatory environment. Keywords: Mesenchymal Stem Cells, PBMCs, proinflammatory cytokines, MLR, immunomodulatory Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune-mediated disease pathogenesis Citation: Trivanović D, Ilić V, Kocić J, Krstić A, Mojsilović S, Okić-Djordjević I, Santibanez J, Bugarski D and Jovčić G (2013). The immunomodulatory activity of human mesenchymal stem cells is related to different tissue origin. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00274 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 12 Mar 2013; Published Online: 22 Aug 2013. * Correspondence: Miss. Drenka Trivanović, Institute for Medical Research, University of Belgrade, Belgrade, Serbia, drenka.trivanovic@imi.bg.ac.rs Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Drenka Trivanović Vesna Ilić Jelena Kocić Aleksandra Krstić Slavko Mojsilović Ivana Okić-Djordjević Juan Francisco Santibanez Diana Bugarski Gordana Jovčić Google Drenka Trivanović Vesna Ilić Jelena Kocić Aleksandra Krstić Slavko Mojsilović Ivana Okić-Djordjević Juan Francisco Santibanez Diana Bugarski Gordana Jovčić Google Scholar Drenka Trivanović Vesna Ilić Jelena Kocić Aleksandra Krstić Slavko Mojsilović Ivana Okić-Djordjević Juan Francisco Santibanez Diana Bugarski Gordana Jovčić PubMed Drenka Trivanović Vesna Ilić Jelena Kocić Aleksandra Krstić Slavko Mojsilović Ivana Okić-Djordjević Juan Francisco Santibanez Diana Bugarski Gordana Jovčić Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Mesenchymal stem cells administered after liver transplantation prevent acute graft-versus-host disease in rats

Acute graft-versus-host disease is a serious and life-threatening complication of liver transplantation (LT) that occurs in 1% to 2% of liver allograft recipients. It is associated with a high mortality rate, and effective therapies are lacking. In our established rat model, a relative decrease in regulatory T cells (Tregs) was previously shown to be associated with acute graft-versus-host disease after liver transplantation (LT-aGVHD). Mesenchymal stem cells (MSCs) have been used to treat graft-versus-host disease after allogeneic hematopoietic stem cell transplantation, and they have been shown to induce Tregs, which have immunomodulatory effects. In this study, when a treatment with donor- or recipient-derived MSCs was administered from day 8 to day 14 after the typical symptoms of LT-aGVHD started, the recipients were not cured, and their survival time was not prolonged. However, when MSCs of different origins were administered from day 0 to day 6 after LT, the recipients survived significantly longer than the control group, and the surviving MSC-treated rats did not show typical LT-aGVHD symptoms. In vivo tracings of carboxyfluorescein diacetate succinimidyl ester-stained MSCs did not show significant accumulations in the target organs after administration. Flow cytometry analysis showed that the Treg ratios in peripheral blood were more higher for the MSC-treated groups versus the control group. More immunohistochemically stained forkhead box P3-positive cells were also found in the intestines of the MSC-treated groups versus the control group. Further investigations of the function of MSCs showed that they could increase the Treg ratio in a mixed lymphocyte reaction (MLR) and lead to a greater reduction in MLR proliferation in vitro. In conclusion, the post-LT administration of MSCs of either donor or recipient origin could prevent the onset of LT-aGVHD in our rat model.

Positional Identity of Murine Mesenchymal Stem Cells Resident in Different Organs Is Determined in the Postsegmentation Mesoderm

Although mesenchymal stem cells (MSCs) of distinct tissue origin have a large number of similarities and differences, it has not been determined so far whether tissue-resident MSCs are the progenies of one ancestor cell lineage or the results of parallel cell developmental events. Here we compared the expression levels of 177 genes in murine MSCs derived from adult and juvenile bone marrow and adult adipose tissue, as well as juvenile spleen, thymus, and aorta wall by quantitative real-time polymerase chain reaction and the results were partially validated at protein level. All MSC lines uniformly expressed a large set of genes including well-known mesenchymal markers, such as α-smooth muscle actin, collagen type I α-chain, GATA6, Mohawk, and vimentin. In contrast, pluripotency genes and the early mesodermal marker T-gene were not expressed. On the other hand, different MSC lines consistently expressed distinct patterns of Hox genes determining the positional identity of a given cell population. Moreover, MSCs of different origin expressed a few other transcription factors also reflecting their topological identity and so the body segment or organ to which they normally contributed in vivo: (1) thymus-derived cells specifically expressed Tbx5 and Pitx2; (2) spleen-derived MSCs were characterized with Tlx1 and Nkx2.5; (3) Pitx1 designated femoral bone marrow cells and (4) En2 appeared in aorta wall-derived MSCs. Thus, MSCs exhibited topographic identity and memory even after long-term cultivation in vitro. On the basis of these results, we suggest that postnatal MSCs isolated from different anatomical sites descend from precursor cells developing in the postsegmentation mesoderm.

Induction of neural-like differentiation in human mesenchymal stem cells derived from bone marrow, fat, spleen and thymus

Mesenchymal stem cells (MSCs) from bone marrow (BM) and sub-cutaneous fat are known to differentiate into neural cells under appropriate stimuli. We describe here the neural-like differentiation of human MSCs obtained from spleen and thymus, induced either with chemical factors or with co-culture with human Schwann cells (Sc). Under the effect of neural differentiation medium, most MSCs from BM, fat, spleen and thymus acquired morphological changes suggestive of cells of astrocytic/neuronal and oligodendroglial lineages with general up-regulation of neural molecules not correlated with morphological changes. The process was transient and reversible, as MSCs recovered basal morphology and phenotype, as well as their multilineage differentiation potential. Thus, we hypothesized that chemical factors may prime MSCs for neural differentiation, by inducing initial and poorly specific changes. By contrast, co-cultures of MSCs of different origin with Sc induced long-lasting and Sc differentiation, i.e., the expression of Sc myelin proteins for up to 12 days. Our results show that a MSC reservoir is present in tissues other than BM and fat, and that MSCs of different origin have similar neural differentiation potential. This evidence provides new insights into BM-like tissue plasticity and may have important implications for future therapeutic interventions in chronic neuropathies.