scholarly journals A molecular classification of human mesenchymal stromal cells

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1845 ◽  
Author(s):  
Florian Rohart ◽  
Elizabeth A. Mason ◽  
Nicholas Matigian ◽  
Rowland Mosbergen ◽  
Othmar Korn ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Interaction Network ◽  
Transcriptome Profiling ◽  
Molecular Classification ◽  
Cell Types ◽  
Gene Expression Omnibus ◽  
Small Sample ◽  
Surface Proteins ◽  
Small Sample Sizes

Mesenchymal stromal cells (MSC) are widely used for the study of mesenchymal tissue repair, and increasingly adopted for cell therapy, despite the lack of consensus on the identity of these cells. In part this is due to the lack of specificity of MSC markers. Distinguishing MSC from other stromal cells such as fibroblasts is particularly difficult using standard analysis of surface proteins, and there is an urgent need for improved classification approaches. Transcriptome profiling is commonly used to describe and compare different cell types; however, efforts to identify specific markers of rare cellular subsets may be confounded by the small sample sizes of most studies. Consequently, it is difficult to derive reproducible, and therefore useful markers. We addressed the question of MSC classification with a large integrative analysis of many public MSC datasets. We derived a sparse classifier (The Rohart MSC test) that accurately distinguished MSC from non-MSC samples with >97% accuracy on an internal training set of 635 samples from 41 studies derived on 10 different microarray platforms. The classifier was validated on an external test set of 1,291 samples from 65 studies derived on 15 different platforms, with >95% accuracy. The genes that contribute to the MSC classifier formed a protein-interaction network that included known MSC markers. Further evidence of the relevance of this new MSC panel came from the high number of Mendelian disorders associated with mutations in more than 65% of the network. These result in mesenchymal defects, particularly impacting on skeletal growth and function. The Rohart MSC test is a simplein silicotest that accurately discriminates MSC from fibroblasts, other adult stem/progenitor cell types or differentiated stromal cells. It has been implemented in thewww.stemformatics.orgresource, to assist researchers wishing to benchmark their own MSC datasets or data from the public domain. The code is available from the CRAN repository and all data used to generate the MSC test is available to download via the Gene Expression Omnibus or the Stemformatics resource.

scholarly journals A Molecular Classification of Human Mesenchymal Stromal Cells

2015 ◽  
Author(s):  
Florian Rohart ◽  
Elizabeth Mason ◽  
Nicholas Matigian ◽  
Rowland Mosbergen ◽  
Othmar Korn ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cultured Cells ◽  
Interaction Network ◽  
Molecular Classification ◽  
Cell Types ◽  
Gene Signature ◽  
Growth Conditions ◽  
Differentiated Cells ◽  
Transcriptional Phenotype

Mesenchymal stromal cells (MSC) are widely used, isolated from a variety of tissues and increasingly adopted for cell therapy, but the identity of these cells is poorly defined and commonalities between MSC from different tissues sources is controversial. Here we undertook a comprehensive review of all public MSC expression studies to assess whether cells derived from different sources shared any common molecular attributes. In doing so, we discovered an over-arching transcriptional phenotype shared by a wide variety of MSC, freshly isolated or cultured cells, and under a variety of growth conditions. We developed a modified variable selection protocol that included cross platform normalisation, and assessment of the selected gene stability and informativeness. A 16-gene signature classified MSC with >97% accuracy, discriminating these from fibroblasts, other adult stem/progenitor cell types and differentiated cells. The genes form part of a protein-interaction network, and mutations in more than 65% of this network were associated with Mendelian disorders of skeletal growth or metabolism. The signature and accompanying datasets are provided as a community resource at www.stemformatics.org resource, and the method is available from the CRAN repository.

scholarly journals What Makes Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells Superior Immunomodulators When Compared to Bone Marrow Derived Mesenchymal Stromal Cells?

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
R. N. Bárcia ◽  
J. M. Santos ◽  
M. Filipe ◽  
M. Teixeira ◽  
J. P. Martins ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Umbilical Cord ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Immune Modulation ◽  
Cell Types ◽  
Surface Proteins ◽  
Umbilical Cord Tissue

MSCs derived from the umbilical cord tissue, termed UCX, were investigated for their immunomodulatory properties and compared to bone marrow-derived MSCs (BM-MSCs), the gold-standard in immunotherapy. Immunogenicity and immunosuppression were assessed by mixed lymphocyte reactions, suppression of lymphocyte proliferation and induction of regulatory T cells. Results showed that UCX were less immunogenic and showed higher immunosuppression activity than BM-MSCs. Further, UCX did not need prior activation or priming to exert their immunomodulatory effects. This was further corroboratedin vivoin a model of acute inflammation. To elucidate the potency differences observed between UCX and BM-MSCs, gene expression related to immune modulation was analysed in both cell types. Several gene expression profile differences were found between UCX and BM-MSCs, namely decreased expression ofHLA-DRA,HO-1,IGFBP1, 4 and 6,ILR1,IL6RandPTGESand increased expression ofCD200,CD273,CD274,IL1B,IL-8,LIFandTGFB2. The latter were confirmed at the protein expression level. Overall, these results show that UCX seem to be naturally more potent immunosuppressors and less immunogenic than BM-MSCs. We propose that these differences may be due to increased levels of immunomodulatory surface proteins such as CD200, CD273, CD274 and cytokines such as IL1β, IL-8, LIF and TGFβ2.

scholarly journals POSTNATAL EXTRA-EMBRYONIC TISSUES AS A SOURCE OF MULTIPLE CELL TYPES FOR REGENERATIVE MEDICINE APPLICATIONS

2017 ◽  
Vol 39 (3) ◽  
pp. 186-190 ◽  
Author(s):  
O S Gubar ◽  
A I Rodnichenko ◽  
R G Vasylie ◽  
A V Zlatska ◽  
D O Zubov
Keyword(s):  
Regenerative Medicine ◽  
Umbilical Cord ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Umbilical Vein ◽  
Cell Types ◽  
Population Doubling ◽  
Embryonic Tissues ◽  
Chorionic Membrane ◽  
Multiple Cell

Aim: We aimed to isolate and characterize the cell types which could be obtained from postnatal extra-embryonic tissues. Materials and Methods: Fresh tissues (no more than 12 h after delivery) were used for enzymatic or explants methods of cell isolation. Obtained cultures were further maintained at 5% oxygen. At P3 cell phenotype was assessed by fluorescence-activated cell sorting, population doubling time was calculated and the multilineage differentiation assay was performed. Results: We have isolated multiple cell types from postnatal tissues. Namely, placental mesenchymal stromal cells from placenta chorionic disc, chorionic membrane mesenchymal stromal cells (ChM-MSC) from free chorionic membrane, umbilical cord MSC (UC-MSC) from whole umbilical cord, human umbilical vein endothelial cells (HUVEC) from umbilical vein, amniotic epithelial cells (AEC) and amniotic MSC (AMSC) from amniotic membrane. All isolated cell types displayed high proliferation rate together with the typical MSC phenotype: CD73+CD90+CD105+CD146+CD166+CD34-CD45-HLA-DR-. HUVEC constitutively expressed key markers CD31 and CD309. Most MSC and AEC were capable of osteogenic and adipogenic differentiation. Conclusion: We have shown that a wide variety of cell types can be easily isolated from extra-embryonic tissues and expanded ex vivo for regenerative medicine applications. These cells possess typical MSC properties and can be considered an alternative for adult MSC obtained from bone marrow or fat, especially for allogeneic use.

scholarly journals Mesenchymal stromal cells-exosomes: a promising cell-free therapeutic tool for wound healing and cutaneous regeneration

2019 ◽  
Vol 7 ◽  
Author(s):  
Peng Hu ◽  
Qinxin Yang ◽  
Qi Wang ◽  
Chenshuo Shi ◽  
Dali Wang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Messenger Rna ◽  
Cell Types ◽  
Skin Wound ◽  
Effector Proteins ◽  
Skin Wound Healing ◽  
New Research

Abstact Cutaneous regeneration at the wound site involves several intricate and dynamic processes which require a series of coordinated interactions implicating various cell types, growth factors, extracellular matrix (ECM), nerves, and blood vessels. Mesenchymal stromal cells (MSCs) take part in all the skin wound healing stages playing active and beneficial roles in animal models and humans. Exosomes, which are among the key products MSCs release, mimic the effects of parental MSCs. They can shuttle various effector proteins, messenger RNA (mRNA) and microRNAs (miRNAs) to modulate the activity of recipient cells, playing important roles in wound healing. Moreover, using exosomes avoids many risks associated with cell transplantation. Therefore, as a novel type of cell-free therapy, MSC-exosome -mediated administration may be safer and more efficient than whole cell. In this review, we provide a comprehensive understanding of the latest studies and observations on the role of MSC-exosome therapy in wound healing and cutaneous regeneration. In addition, we address the hypothesis of MSCs microenvironment extracellular vesicles (MSCs-MEVs) or MSCs microenvironment exosomes (MSCs-MExos) that need to take stock of and solved urgently in the related research about MSC-exosomes therapeutic applications. This review can inspire investigators to explore new research directions of MSC-exosome therapy in cutaneous repair and regeneration.

scholarly journals Exogenous Delivery of Link N mRNA into Chondrocytes and MSCs—The Potential Role in Increasing Anabolic Response

2019 ◽  
Vol 20 (7) ◽  
pp. 1716 ◽  
Author(s):  
Gauri Tendulkar ◽  
Sabrina Ehnert ◽  
Vrinda Sreekumar ◽  
Tao Chen ◽  
Hans-Peter Kaps ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Intervertebral Disc ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cell Types ◽  
Bmp Signaling ◽  
Anabolic Response ◽  
Health And Social Care ◽  
Intervertebral Disc Regeneration ◽  
Exogenous Delivery

Musculoskeletal disorders, such as osteoarthritis and intervertebral disc degeneration are causes of morbidity, which concomitantly burdens the health and social care systems worldwide, with massive costs. Link N peptide has recently been described as a novel anabolic stimulator for intervertebral disc repair. In this study, we analyzed the influence on anabolic response, by delivering synthetic Link N encoding mRNA into primary human chondrocytes and mesenchymal stromal cells (SCP1 cells), Furthermore, both cell types were seeded on knitted titanium scaffolds, and the influence of Link N peptide mRNA for possible tissue engineering applications was investigated. Synthetic modified Link N mRNA was efficiently delivered into both cell types and cell transfection resulted in an enhanced expression of aggrecan, Sox 9, and type II collagen with a decreased expression of type X collagen. Interestingly, despite increased expression of BMP2 and BMP7, BMP signaling was repressed and TGFβ signaling was boosted by Link N transfection in mesenchymal stromal cells, suggesting possible regulatory mechanisms. Thus, the exogenous delivery of Link N peptide mRNA into cells augmented an anabolic response and thereby increased extracellular matrix synthesis. Considering these findings, we suppose that the cultivation of cells on knitted titanium scaffolds and the exogenous delivery of Link N peptide mRNA into cells could mechanically support the stability of tissue-engineered constructs and improve the synthesis of extracellular matrix by seeded cells. This method can provide a potent strategy for articular cartilage and intervertebral disc regeneration.

scholarly journals Amniotic Mesenchymal Stromal Cells Exhibit Preferential Osteogenic and Chondrogenic Differentiation and Enhanced Matrix Production Compared With Adipose Mesenchymal Stromal Cells

2017 ◽  
Vol 45 (11) ◽  
pp. 2637-2646 ◽  
Author(s):  
Natasha Topoluk ◽  
Richard Hawkins ◽  
John Tokish ◽  
Jeremy Mercuri
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Chondrogenic Differentiation ◽  
Cell Types ◽  
Cell Counting ◽  
Gene Transcript ◽  
Differentiation Potential ◽  
Musculoskeletal Tissue ◽  
Cell Groups ◽  
And Cartilage

Background: Therapeutic efficacy of various mesenchymal stromal cell (MSC) types for orthopaedic applications is currently being investigated. While the concept of MSC therapy is well grounded in the basic science of healing and regeneration, little is known about individual MSC populations in terms of their propensity to promote the repair and/or regeneration of specific musculoskeletal tissues. Two promising MSC sources, adipose and amnion, have each demonstrated differentiation and extracellular matrix (ECM) production in the setting of musculoskeletal tissue regeneration. However, no study to date has directly compared the differentiation potential of these 2 MSC populations. Purpose: To compare the ability of human adipose- and amnion-derived MSCs to undergo osteogenic and chondrogenic differentiation. Study Design: Controlled laboratory study. Methods: MSC populations from the human term amnion were quantified and characterized via cell counting, histologic assessment, and flow cytometry. Differentiation of these cells in comparison to commercially purchased human adipose-derived mesenchymal stromal cells (hADSCs) in the presence and absence of differentiation media was evaluated via reverse transcription polymerase chain reaction (PCR) for bone and cartilage gene transcript markers and histology/immunohistochemistry to examine ECM production. Analysis of variance and paired t tests were performed to compare results across all cell groups investigated. Results: The authors confirmed that the human term amnion contains 2 primary cell types demonstrating MSC characteristics—(1) human amniotic epithelial cells (hAECs) and (2) human amniotic mesenchymal stromal cells (hAMSCs)—and each exhibited more than 90% staining for MSC surface markers (CD90, CD105, CD73). Average viable hAEC and hAMSC yields at harvest were 2.3 × 106 ± 3.7 × 105 and 1.6 × 106 ± 4.7 × 105 per milliliter of amnion, respectively. As well, hAECs and hAMSCs demonstrated significantly greater osteocalcin ( P = .025), aggrecan ( P < .0001), and collagen type 2 ( P = .044) gene expression compared with hADSCs, respectively, after culture in differentiation medium. Moreover, both hAECs and hAMSCs produced significantly greater quantities of mineralized ( P < .0001) and cartilaginous ( P = .0004) matrix at earlier time points compared with hADSCs when cultured under identical osteogenic and chondrogenic differentiation conditions, respectively. Conclusion: Amnion-derived MSCs demonstrate a greater differentiation potential toward bone and cartilage compared with hADSCs. Clinical Relevance: Amniotic MSCs may be the source of choice in the regenerative treatment of bone or osteochondral musculoskeletal disease. They show significantly higher yields and better differentiation toward these tissues than MSCs derived from adipose.

scholarly journals Co-culture with leukemia cells decreases proliferation and increases chemoprotective capacity of normal mesenchymal stromal cells

2020 ◽  
Author(s):  
Ruixia Hou ◽  
Wanfang Yang ◽  
Yaofang Zhang ◽  
Xiuhua Chen ◽  
Fanggang Ren ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Healthy Donor ◽  
Pearson Correlation ◽  
Correlation Coefficients ◽  
Cell Types ◽  
Leukemia Cells ◽  
Cell Counts ◽  
Functional Components

Abstract Background Bone marrow mesenchymal stromal cells (BM-MSCs) are essential structural and functional components of the BM microenvironment and play an important role in acute myeloid leukemia (AML) pathogenesis. BM-MSCs isolated from AML patients (AML-MSCs) show distinct signatures from normal BM-MSCs. However, the exact abnormalities of AML-MSCs and the origin of these abnormalities are still unknown.Methods In this study, we evaluated the proliferative activity of AML-MSCs, and the influence of leukemia cells (LCs) on BM-MSCs. These two cell types were co-cultured using an in vitro co-culture system, and the biological functions of AML-MSCs, healthy donor derived MSCs (HD-MSCs), and LC-treated HD-MSCs (LCtrHD-MSCs) were compared by flow cytometry, and CCK-8 and chemotaxis assays. Student t-test (between two groups) and one-way ANOVA (more than 2 groups) were used to compare differences. Pearson correlation coefficients were used to assess correlations between two factors.Results AML-MSCs display a significant proliferative deficiency, which correlates with primary leukemic blast cell counts but not with patients’ age. Inhibition of BM-MSC proliferation could be induced by leukemia cells through direct contact. Co-cultured leukemia cells also increase expression of several inflammatory cytokines, and chemokines in BM-MSCs. Furthermore, LCtrHD-MSCs reduced apoptosis, and increased migration and chemoresistance in co-cultured AML cells, comparable with AML-MSCs.Conclusions Our results showed that leukemia cells can induce healthy donor derived BM-MSCs to exhibit AML-MSC-like characteristics and indicated that AML-MSC abnormalities may be partly induced by leukemia cells.

Extracellular Vesicles Isolated from Mesenchymal Stromal Cells Primed with Hypoxia: Novel strategy in Regenerative Medicine

2020 ◽  
Vol 15 ◽  
Author(s):  
Shalmali Pendse ◽  
Vaijayanti Kale ◽  
Anuradha Vaidya
Keyword(s):  
Extracellular Vesicles ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Cell Types ◽  
Molecular Profile ◽  
Cell Contact ◽  
Hematopoietic Stem

: Mesenchymal stromal cells (MSCs) regulate other cell types through a strong paracrine component called the secretome, comprising of several bioactive entities. The composition of the MSCs’ secretome is dependent upon the microenvironment in which they thrive, and hence, it could be altered by pre-conditioning the MSCs during in vitro culture. The primary aim of this review is to discuss various strategies that are being used for pre-conditioning of MSCs, also known as “priming of MSCs”, in the context of improving their therapeutic potential. Several studies have underscored the importance of extracellular vesicles (EVs) derived from primed MSCs in improving their efficacy in the treatment of various diseases. We have previously shown that co-culturing hematopoietic stem cells (HSCs) with hypoxiaprimed MSCs improves their engraftment potential. Now the question we pose is would priming of MSCs with hypoxiafavorably alter theirsecretome and would this altered secretome work as effectively as the cell to cell contact did? Here we review the current strategies of using the secretome, specifically the EVs (microvesicles and exosomes), collected from the primed MSCs with the intention of expanding HSCs ex vivo. We speculate that an effective priming of MSCs in vitrocould modulate the molecular profile of their secretome, which could eventually be used as a cell-free biologic in clinical settings.

scholarly journals Mesenchymal Stromal Cells Support Endometriotic Stromal CellsIn Vitro

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Fawaz Abomaray ◽  
Sebastian Gidlöf ◽  
Bartosz Bezubik ◽  
Mikael Engman ◽  
Cecilia Götherström
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Inflammatory Diseases ◽  
Umbilical Vein ◽  
Cell Types ◽  
Tube Formation ◽  
Migration And Invasion ◽  
Endometrial Cells ◽  
Umbilical Vein Endothelial Cells

Endometriosis is an inflammatory disease marked by ectopic growth of endometrial cells. Mesenchymal stromal cells (MSC) have immunosuppressive properties that have been suggested as a treatment for inflammatory diseases. Therefore, the aim herein was to examine effects of allogeneic MSC on endometriosis-derived cellsin vitroas a potential therapy for endometriosis. MSC from allogeneic adipose tissue (Ad-MSC) and stromal cells from endometrium (ESCendo) and endometriotic ovarian cysts (ESCcyst) from women with endometriosis were isolated. The effects of Ad-MSC on ESCendoand ESCcystwere investigated usingin vitroproliferation, apoptosis, adhesion, tube formation, migration, and invasion assays. Ad-MSC significantly increased proliferation of ESC compared to untreated controls. Moreover, Ad-MSC significantly decreased apoptosis and increased survival of ESC. Ad-MSC significantly increased adhesion of ESCendoand not ESCcyston fibronectin. Conditioned medium from cocultures of Ad-MSC and ESC significantly increased tube formation of human umbilical vein endothelial cells on matrigel. Ad-MSC may significantly increase migration of ESCcystand did not increase invasion of both cell types. The data suggest that allogeneic Ad-MSC should not be considered as a potential therapy for endometriosis, because they may support the pathology by maintaining and increasing growth of ectopic endometrial tissue.

scholarly journals Mechanisms of T-Cell Immunosuppression by Mesenchymal Stromal Cells: What Do We Know So Far?

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Rodrigo Haddad ◽  
Felipe Saldanha-Araujo
Keyword(s):  
T Cell ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cell Types ◽  
Biological Properties ◽  
T Cell Response ◽  
Cell Contact ◽  
Inflammatory Microenvironment ◽  
And Function ◽  
Cellular Immune

Mesenchymal stromal cells (MSCs) are multipotent cells, which can give rise to several cell types including osteoblasts, adipocytes, and chondroblasts. These cells can be found in a variety of adult and fetal tissues, such as bone marrow, adipose tissue, cord blood, and placenta. In recent years, the biological properties of MSCs have attracted the attention of researchers worldwide due to their potential application for treating a series of clinical situations. Among these properties, special attention should be given to the immunoregulatory potential of those cells. MSCs are able to act on all cells of the immune system, which includes the capacity to inhibit the proliferation and function of T-cells. This feature renders them natural candidates to treat several diseases in which cellular immune response is exacerbated. In this review, we outline the main mechanisms by which MSCs immunosuppress T-cell response, focusing on cell-cell contact, secretion of soluble factors, and regulatory T-cell generation. The influence of surface markers in the immunosuppression process and features of MSCs isolated from different sources are also discussed. Finally, the influences of toll-like receptors and cytokines on the inflammatory microenvironment are highlighted regarding the activation of MSCs to exert their immunoregulatory function.

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