scholarly journals Human Tonsil-Derived Mesenchymal Stromal Cells Maintain Proliferating and ROS-Regulatory Properties via Stanniocalcin-1

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 636
Author(s):  
Yoojin Seo ◽  
Tae-Hoon Shin ◽  
Ji-Su Ahn ◽  
Su-Jeong Oh ◽  
Ye Young Shin ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Critical Role ◽  
Cell Types ◽  
Inhibitory Effect ◽  
Ros Generation ◽  
Human Tonsil ◽  
Differentiation Potential ◽  
Proliferation Capacity

Mesenchymal stromal cells (MSCs) from various sources exhibit different potential for stemness and therapeutic abilities. Recently, we reported a unique MSCs from human palatine tonsil (TMSCs) and their superior proliferation capacity compared to MSCs from other sources. However, unique characteristics of each MSC are not yet precisely elucidated. We investigated the role of stanniocalcin-1 (STC1), an anti-oxidative hormone, in the functions of TMSCs. We found that STC1 was highly expressed in TMSC compared with MSCs from bone marrow or adipose tissue. The proliferation, senescence and differentiation of TMSCs were assessed after the inhibition of STC1 expression. STC1 inhibition resulted in a significant decrease in the proliferation of TMSCs and did not affect the differentiation potential. To reveal the anti-oxidative ability of STC1 in TMSCs themselves or against other cell types, the generation of mitochondrial reactive oxygen species (ROS) in TMSC or ROS-mediated production of interleukin (IL)-1β from macrophage-like cells were detected. Interestingly, the basal level of ROS generation in TMSCs was significantly elevated after STC1 inhibition. Moreover, down-regulation of STC1 impaired the inhibitory effect of TMSCs on IL-1β production in macrophages. Taken together, these findings indicate that STC1 is highly expressed in TMSCs and plays a critical role in proliferating and ROS-regulatory abilities.

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 Human Mesenchymal Stromal Cells Transplantation May Enhance or Inhibit 4T1 Murine Breast Adenocarcinoma through Different Approaches

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
T. Jazedje ◽  
A. L. Ribeiro ◽  
M. Pellati ◽  
H. M. de Siqueira Bueno ◽  
G. Nagata ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cell Lineage ◽  
Inhibitory Effect ◽  
Mammary Adenocarcinoma ◽  
Breast Adenocarcinoma ◽  
Human Fallopian Tube ◽  
Initial Stage ◽  
First Time

The use of Mesenchymal Stromal Cells (MSCs) aiming to treat cancer has shown very contradictory results. In an attempt to clarify the contradictory results reported in the literature and the possible role of human fallopian tube Mesenchymal Stromal Cells (htMSCs) against breast cancer, the aim of this study was to evaluate the clinical effect of htMSCs in murine mammary adenocarcinoma using two different approaches: (1) coinjections of htMSCs and 4T1 murine tumor cell lineage and (2) injections of htMSCs in mice at the initial stage of mammary adenocarcinoma development. Coinjected animals had a more severe course of the disease and a reduced survival, while tumor-bearing animals treated with 2 intraperitoneal injections of 106htMSCs showed significantly reduced tumor growth and increased lifespan as compared with control animals. Coculture of htMSCs and 4T1 tumor cells revealed an increase in IL-8 and MCP-1 and decreased VEGF production. For the first time, we show that MSCs isolated from a single source and donor when injected in the same animal model and tumor can lead to opposite results depending on the experimental protocol. Also, our results demonstrated that htMSCs can have an inhibitory effect on the development of murine mammary adenocarcinoma.

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 Lymphoid Tissue Mesenchymal Stromal Cells in Development and Tissue Remodeling

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Luca Genovese ◽  
Andrea Brendolan
Keyword(s):  
Immune Responses ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cell Activation ◽  
Critical Role ◽  
Tissue Remodeling ◽  
Stromal Microenvironment ◽  
Inflammatory Conditions ◽  
Secondary Lymphoid Organs

Secondary lymphoid organs (SLOs) are sites that facilitate cell-cell interactions required for generating adaptive immune responses. Nonhematopoietic mesenchymal stromal cells have been shown to play a critical role in SLO function, organization, and tissue homeostasis. The stromal microenvironment undergoes profound remodeling to support immune responses. However, chronic inflammatory conditions can promote uncontrolled stromal cell activation and aberrant tissue remodeling including fibrosis, thus leading to tissue damage. Despite recent advancements, the origin and role of mesenchymal stromal cells involved in SLO development and remodeling remain unclear.

scholarly journals Senescence-associated metabolomic phenotype in primary and iPSC-derived mesenchymal stromal cells

2019 ◽  
Author(s):  
Eduardo Fernandez-Rebollo ◽  
Julia Franzen ◽  
Jonathan Hollmann ◽  
Alina Ostrowska ◽  
Matteo Oliverio ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Replicative Senescence ◽  
Cell Types ◽  
Cellular Aging ◽  
Metabolic Switch ◽  
Differentiation Potential ◽  
Long Term Culture ◽  
Functional Changes

Long-term culture of primary cells is reflected by functional and secretory changes, which ultimately result in replicative senescence. In contrast, induced pluripotent stem cells (iPSCs) do not reveal any signs of cellular aging while in the pluripotency state, whereas little is known how they senesce upon differentiation. Furthermore, it is largely unclear how the metabolome of cells changes during replicative senescence and if such changes are consistent across different cell types. In this study, we have directly compared culture expansion of primary mesenchymal stromal cells (MSCs) and iPSC-derived MSCs (iMSCs) until they reached growth arrest after a mean of 21 and 17 cumulative population doublings, respectively. Both cell types acquired similar changes in morphology, in vitro differentiation potential, up-regulation of senescence-associated beta-galactosidase, and senescence-associated DNA methylation changes. Furthermore, MSCs and iMSCs revealed overlapping gene expression changes during culture expansion, particularly in functional categories related to metabolic processes. We subsequently compared the metabolome of MSCs and iMSCs at early and senescent passages and observed various significant and overlapping senescence-associated changes in both cell types, including down-regulation of nicotinamide ribonucleotide and up-regulation of orotic acid. Replicative senescence of both cell types was consistently reflected by the metabolic switch from oxidative to glycolytic pathways. Taken together, long-term culture of iPSC-derived MSCs evokes very similar molecular and functional changes as observed in primary MSCs. Replicative senescence is associated with a highly reproducible senescence-associated metabolomics phenotype, which may be used to monitor the state of cellular aging.

scholarly journals Toll-Like Receptors and Dental Mesenchymal Stromal Cells

2021 ◽  
Vol 2 ◽  
Author(s):  
Oleh Andrukhov
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Inflammatory Diseases ◽  
Toll Like Receptors ◽  
Tlr Signaling ◽  
Differentiation Potential ◽  
Proinflammatory Mediators ◽  
Promising Tool ◽  
And Function

Dental mesenchymal stromal cells (MSCs) are a promising tool for clinical application in and beyond dentistry. These cells possess multilineage differentiation potential and immunomodulatory properties. Due to their localization in the oral cavity, these cells could sometimes be exposed to different bacteria and viruses. Dental MSCs express various Toll-like receptors (TLRs), and therefore, they can recognize different microorganisms. The engagement of TLRs in dental MSCs by various ligands might change their properties and function. The differentiation capacity of dental MSCs might be either inhibited or enhanced by TLRs ligands depending on their nature and concentrations. Activation of TLR signaling in dental MSCs induces the production of proinflammatory mediators. Additionally, TLR ligands alter the immunomodulatory ability of dental MSCs, but this aspect is still poorly explored. Understanding the role of TLR signaling in dental MSCs physiology is essential to assess their role in oral homeostasis, inflammatory diseases, and tissue regeneration.

scholarly journals Genetic engineering of mesenchymal stromal cells for cancer therapy: turning partners in crime into Trojan horses

2016 ◽  
Vol 1 (1) ◽  
pp. 19-32 ◽  
Author(s):  
Hanno Niess ◽  
Michael N. Thomas ◽  
Tobias S. Schiergens ◽  
Axel Kleespies ◽  
Karl-Walter Jauch ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Current Knowledge ◽  
Cell Types ◽  
The Body ◽  
Biological Functions ◽  
Connective Tissues ◽  
Differentiation Potential ◽  
Underlying Mechanisms ◽  
Do So

AbstractMesenchymal stromal cells (MSCs) are adult progenitor cells with a high migratory and differentiation potential, which influence a broad range of biological functions in almost every tissue of the body. Among other mechanisms, MSCs do so by the secretion of molecular cues, differentiation toward more specialized cell types, or influence on the immune system. Expanding tumors also depend on the contribution of MSCs to building a supporting stroma, but the effects of MSCs appear to go beyond the mere supply of connective tissues. MSCs show targeted “homing” toward growing tumors, which is then followed by exerting direct and indirect effects on cancer cells. Several research groups have developed novel strategies that make use of the tumor tropism of MSCs by engineering them to express a transgene that enables an attack on cancer growth. This review aims to familiarize the reader with the current knowledge about MSC biology, the existing evidence for MSC contribution to tumor growth with its underlying mechanisms, and the strategies that have been developed using MSCs to deploy an anticancer therapy.

scholarly journals Galectin-3 Knockdown Impairs Survival, Migration, and Immunomodulatory Actions of Mesenchymal Stromal Cells in a Mouse Model of Chagas Disease Cardiomyopathy

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Bruno Solano de Freitas Souza ◽  
Kátia Nunes da Silva ◽  
Daniela Nascimento Silva ◽  
Vinícius Pinto Costa Rocha ◽  
Bruno Diaz Paredes ◽  
...  
Keyword(s):  
Immune Response ◽  
Chagas Disease ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Type I Collagen ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Type I ◽  
Differentiation Potential ◽  
Galectin 3

Therapies based on transplantation of mesenchymal stromal cells (MSC) hold promise for the management of inflammatory disorders. In chronic Chagas disease cardiomyopathy (CCC), caused by chronic infection with Trypanosoma cruzi, the exacerbated immune response plays a critical pathophysiological role and can be modulated by MSC. Here, we investigated the role of galectin-3 (Gal-3), a beta-galactoside-binding lectin with several actions on immune responses and repair process, on the immunomodulatory potential of MSC. Gal-3 knockdown in MSC did not affect the immunophenotype or differentiation potential. However, Gal-3 knockdown MSC showed decreased proliferation, survival, and migration. Additionally, when injected intraperitoneally into mice with CCC, Gal-3 knockdown MSC showed impaired migration in vivo. Transplantation of control MSC into mice with CCC caused a suppression of cardiac inflammation and fibrosis, reducing expression levels of CD45, TNFα, IL-1β, IL-6, IFNγ, and type I collagen. In contrast, Gal-3 knockdown MSC were unable to suppress the immune response or collagen synthesis in the hearts of mice with CCC. Finally, infection with T. cruzi demonstrated parasite survival in wild-type but not in Gal-3 knockdown MSC. These findings demonstrate that Gal-3 plays a critical role in MSC survival, proliferation, migration, and therapeutic potential in CCC.

Phenotypic and Functional Characterization of Mesenchymal Stromal Cells Derived from CD271+- Bone Marrow Mononuclear Cells and Mesenchymal Stromal Cells Derived through Plastic Adherence.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1921-1921
Author(s):  
Selim Kuci ◽  
Kathrin Puetsch ◽  
Zyrafete Kuci ◽  
Sabine Huenecke ◽  
Hermann Kreyenberg ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Mononuclear Cells ◽  
Functional Characterization ◽  
In Vivo Studies ◽  
Bone Marrow Mononuclear Cells ◽  
Cell Surface Antigens ◽  
Differentiation Potential ◽  
Proliferation Capacity

Abstract Mesenchymal stromal cells (MSCs) are non- hematopoietic multipotent cells which can be derived from bone marrow mononuclear cells either by plastic adherence (PA-MSCs) or by a positive selection with antibodies against cell surface antigens expressed by MSC-progenitor cells (CD271, CD73, CD146, CD105, CD166, SSEA-4 and recently GD2). In this study, we compare the phenotype, proliferation potential, differentiation potential, the cytokine expression pattern and inhibitory potential of MSC- derived by plastic adherence and MSCs derived from positively selected CD271+ bone marrow mononuclear cells (BM-MNCs). According to CFU-F assay, the enriched CD271+ BM cells possess a significantly higher frequency (2952 per 1×106 BM cells) compared to PA-MSCs (21 per 1×106 BM cells). Phenotypically, both populations expressed high levels of common MSC antigens such as CD73, CD105, CD44, CD166, CD90, HLA-Class I and were negative for CD34, CD133, and CD14. Compared to PA-MSCs, CD271+ BM cells after the isolation express high levels of the hematopoietic antigen CD45 which is down- regulated within the first passage and HLA-DR, which remains constant through many passages. These cells have a 10- to 1000-fold higher proliferation capacity compared to PA- MSCs. However, both populations differentiated in vitro along adipogenic, chondrogenic and osteogenic lineage. In MLR, both populations significantly suppressed the proliferation of PHA- stimulated allogeneic T- lymphocytes at the ratio 10: 1 (MSCs:T-cells). However, CD271+ BM- derived MSCs were more efficient in secreting IFN-γ, IL-1β, IL-2, IL-4, GM-CSF and TNF-α, whereas PA- MSCs secreted significantly more IL-6 and IL-8 than CD271+ BM- derived MSCs. Ongoing in vivo studies with immunodeficient NOD/SCID mice will show the whole potential of both population in the improvement of engraftment of mobilized peripheral blood hemaatopoietic CD133+ cells. Based on their higher frequency and proliferation capacity we suggest that CD271+ BM- cells may represent a better source than PA- MSCs in order to generate bulk quantities of MSCs for clinical applications.

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