scholarly journals Differentiation of Motor Neuron-Like Cells from Tonsil-Derived Mesenchymal Stem Cells and Their Possible Application to Neuromuscular Junction Formation

2019 ◽  
Vol 20 (11) ◽  
pp. 2702 ◽  
Author(s):  
Saeyoung Park ◽  
Ji Yeon Kim ◽  
Seoha Myung ◽  
Namhee Jung ◽  
Yeonzi Choi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Motor Neurons ◽  
Neuromuscular Junctions ◽  
Genetic Mutation ◽  
Human Tonsil ◽  
Differentiation Potential ◽  
Cell Therapies ◽  
Human Skeletal Muscle Cells ◽  
Wide Range

Human tonsil-derived mesenchymal stem cells (T-MSCs) are newly identified MSCs and present typical features of MSCs, including having the differentiation capacity into the three germ layers and excellent proliferation capacity. They are easily sourced and are useful for stem cell therapy in various disease states. We previously reported that T-MSCs could be differentiated into skeletal myocytes and Schwann-like cells; therefore, they are a promising candidate for cell therapies for neuromuscular disease. Motor neurons (MNs), which regulate spontaneous behavior, are affected by a wide range of MN diseases (MNDs) for which there are no effective remedies. We investigated the differentiation potential of MN-like cells derived from T-MSCs (T-MSC-MNCs) for application to therapy of MNDs. After the process of MN differentiation, the expression of MN-related markers, including Islet 1, HB9/HLXB9 (HB9), and choline acetyltransferase (ChAT), was increased when compared with undifferentiated T-MSCs. The secretion of acetylcholine to the conditioned medium was significantly increased after MN differentiation. We cocultured T-MSC-MNCs and human skeletal muscle cells, and confirmed the presence of the acetylcholine receptor clusters, which demonstrated the formation of neuromuscular junctions. The potential functional improvements afforded by these T-MSC-MNCs could be useful in the treatment of MNDs caused by genetic mutation, viral infection, or environmental problems.

scholarly journals Cell Adhesion and Long-Term Survival of Transplanted Mesenchymal Stem Cells: A Prerequisite for Cell Therapy

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Seahyoung Lee ◽  
Eunhyun Choi ◽  
Min-Ji Cha ◽  
Ki-Chul Hwang
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Adhesion ◽  
Therapeutic Potential ◽  
Term Survival ◽  
Differentiation Potential ◽  
Cell Therapies ◽  
Beneficial Effects ◽  
Genetic Modifications ◽  
Preclinical And Clinical Studies

The literature provides abundant evidence that mesenchymal stem cells (MSCs) are an attractive resource for therapeutics and have beneficial effects in regenerating injured tissues due to their self-renewal ability and broad differentiation potential. Although the therapeutic potential of MSCs has been proven in both preclinical and clinical studies, several questions have not yet been addressed. A major limitation to the use of MSCs in clinical applications is their poor viability at the site of injury due to the harsh microenvironment and to anoikis driven by the loss of cell adhesion. To improve the survival of the transplanted MSCs, strategies to regulate apoptotic signaling and enhance cell adhesion have been developed, such as pretreatment with cytokines, growth factors, and antiapoptotic molecules, genetic modifications, and hypoxic preconditioning. More appropriate animal models and a greater understanding of the therapeutic mechanisms of MSCs will be required for their successful clinical application. Nevertheless, the development of stem cell therapies using MSCs has the potential to treat degenerative diseases. This review discusses various approaches to improving MSC survival by inhibiting anoikis.

scholarly journals In VitroEffects of Strontium on Proliferation and Osteoinduction of Human Preadipocytes

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
V. Nardone ◽  
R. Zonefrati ◽  
C. Mavilia ◽  
C. Romagnoli ◽  
S. Ciuffi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Tissue Regeneration ◽  
Cell Therapies ◽  
Cellular Models ◽  
Alp Activity ◽  
Wide Range ◽  
Marrow Mesenchymal Stem Cells

Development of tools to be used forin vivobone tissue regeneration focuses on cellular models and differentiation processes. In searching for all the optimal sources, adipose tissue-derived mesenchymal stem cells (hADSCs or preadipocytes) are able to differentiate into osteoblasts with analogous characteristics to bone marrow mesenchymal stem cells, producing alkaline phosphatase (ALP), collagen, osteocalcin, and calcified nodules, mainly composed of hydroxyapatite (HA). The possibility to influence bone differentiation of stem cells encompasses local and systemic methods, including the use of drugs administered systemically. Among the latter, strontium ranelate (SR) represents an interesting compound, acting as an uncoupling factor that stimulates bone formation and inhibits bone resorption. The aim of our study was to evaluate thein vitroeffects of a wide range of strontium (Sr2+) concentrations on proliferation, ALP activity, and mineralization of a novel finite clonal hADSCs cell line, named PA20-h5. Sr2+promoted PA20-h5 cell proliferation while inducing the increase of ALP activity and gene expression as well as HA production duringin vitroosteoinduction. These findings indicate a role for Sr2+in supporting bone regeneration during the process of skeletal repair in general, and, more specifically, when cell therapies are applied.

scholarly journals Interaction between Mesenchymal Stem Cells and Intervertebral Disc Microenvironment: From Cell Therapy to Tissue Engineering

2019 ◽  
Vol 2019 ◽  
pp. 1-15
Author(s):  
Gianluca Vadalà ◽  
Luca Ambrosio ◽  
Fabrizio Russo ◽  
Rocco Papalia ◽  
Vincenzo Denaro
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Intervertebral Disc ◽  
Cell Activity ◽  
Trophic Factors ◽  
Anatomical Location ◽  
Cell Therapies ◽  
Wide Range

Low back pain (LBP) in one of the most disabling symptoms affecting nearly 80% of the population worldwide. Its primary cause seems to be intervertebral disc degeneration (IDD): a chronic and progressive process characterized by loss of viable cells and extracellular matrix (ECM) breakdown within the intervertebral disc (IVD) especially in its inner region, the nucleus pulposus (NP). Over the last decades, innovative biological treatments have been investigated in order to restore the original healthy IVD environment and achieve disc regeneration. Mesenchymal stem cells (MSCs) have been widely exploited in regenerative medicine for their capacity to be easily harvested and be able to differentiate along the osteogenic, chondrogenic, and adipogenic lineages and to secrete a wide range of trophic factors that promote tissue homeostasis along with immunomodulation and anti-inflammation. Several in vitro and preclinical studies have demonstrated that MSCs are able to acquire a NP cell-like phenotype and to synthesize structural components of the ECM as well as trophic and anti-inflammatory mediators that may support resident cell activity. However, due to its unique anatomical location and function, the IVD presents distinctive features: avascularity, hypoxia, low glucose concentration, low pH, hyperosmolarity, and mechanical loading. Such conditions establish a hostile microenvironment for both resident and exogenously administered cells, which limited the efficacy of intradiscal cell therapy in diverse investigations. This review is aimed at describing the characteristics of the healthy and degenerated IVD microenvironment and how such features influence both resident cells and MSC viability and biological activity. Furthermore, we focused on how recent research has tried to overcome the obstacles coming from the IVD microenvironment by developing innovative cell therapies and functionalized bioscaffolds.

scholarly journals Isolation and Localization of Mesenchymal Stem Cells in Human Palatine Tonsil by W5C5 (SUSD2)

2016 ◽  
Vol 38 (1) ◽  
pp. 83-93 ◽  
Author(s):  
Byung-Joo Lee ◽  
Dae-Woon Kang ◽  
Hee-Young Park ◽  
Ji-Sun Song ◽  
Ji-Min Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stromal Cells ◽  
Human Tonsil ◽  
Differentiation Potential ◽  
Surface Marker Expression ◽  
Single Marker ◽  
Forming Efficiency ◽  
Perivascular Area ◽  
Proliferation Potential

Background/Aims: Although tonsil-mesenchymal stem cells (T-MSCs) have been studied as a new autologous or homologous source of MSCs, research on specific markers of MSCs and localization for purified T-MSC isolation has not yet been reported. This study investigates the expression of W5C5 (SUSD2) in tonsil stromal cells and the colony-forming ability and differentiation potential of W5C5+ cells to determine the usefulness of W5C5+ MSCs as a marker that can be used for the purification of T-MSCs. In addition, the location of W5C5+ cells expressed in the tonsil tissues is examined. Methods: T-MSCs were isolated from the tonsillar tissues of 12 patients undergoing tonsillectomy. The colony-forming ability, surface markers, proliferation potential, and differentiation capacities of purified W5C5+ MSCs, W5C5- MSCs, and unselected T-MSCs were evaluated. The location of the W5C5+ cells in the tonsillar tissues was also investigated by immunohistochemistry. Results: W5C5 was expressed in 2.5±0.4% of fresh human tonsil stromal cells. W5C5+ cells formed many colonies, but W5C5- cells did not form any colonies. The colony-forming number of W5C5+ cells (74.4 ± 9.8) was significantly higher than that of unselected tonsil stromal cells (23.6 ± 3.7). However, the differences in proliferation potential, surface marker expression, and differentiation potential between W5C5+ T-MSCs and unselected T-MSCs were not significant. W5C5+ cells were identified in the perivascular area around the blood vessels. Conclusion: W5C5+ T-MSCs possessed typical MSC properties with high colony-forming efficiency, and niches of W5C5+ T-MSCs were located in the perivascular area of tonsil tissues. These findings suggest that W5C5 is a useful single marker for the isolation of purified T-MSCs.

scholarly journals TNF-α Priming Elicits Robust Immunomodulatory Potential of Human Tonsil-Derived Mesenchymal Stem Cells to Alleviate Murine Colitis

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 561
Author(s):  
Tae-Hoon Shin ◽  
Ji-Su Ahn ◽  
Su-Jeong Oh ◽  
Ye Young Shin ◽  
Ji Won Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Inflammatory Diseases ◽  
Human Tonsil ◽  
Cell Therapies ◽  
Promising Tool ◽  
Tnf Α ◽  
Pre Treatment ◽  
Specific Tissue

Mesenchymal stem cells (MSCs) have been spotlighted in the field of cell therapies as a promising tool for the treatment of intractable inflammatory diseases. However, their therapeutic potency still shows a gap between preclinical and clinical settings, and distinctive characteristics of specific tissue-derived MSCs and definitive ways to maximize their beneficial functions have not been fully elucidated yet. We previously identified the unique MSCs population from human palatine tonsil (TMSCs) and revealed their superior properties in proliferation and ROS regulation. Based on these findings, we explored further characteristics of TMSCs particularly focused on immunomodulatory function. We found the merit of TMSCs as a therapeutic agent that retains favorable MSCs properties until relatively late passages and revealed that pre-treatment of TNF-α can enhance the immunomodulatory abilities of TMSCs through the upregulation of the PTGS2/PGE2 axis. TMSCs primed with TNF-α effectively restrained the proliferation and differentiation of T lymphocytes and macrophages in vitro, and more interestingly, these TNF-α-licensed TMSCs exhibited significant prophylactic and therapeutic efficacy in a murine model of autoimmune-mediated acute colitis via clinical and histopathological assessment compared to unprimed naïve TMSCs. These findings provide novel insight into the optimization and standardization of MSCs-based anti-inflammatory therapies, especially targeting inflammatory bowel disease (IBD).

scholarly journals Isolation and Molecular Characterization of Amniotic Fluid-Derived Mesenchymal Stem Cells Obtained from Caesarean Sections

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Lucas-Sebastian Spitzhorn ◽  
Md Shaifur Rahman ◽  
Laura Schwindt ◽  
Huyen-Tran Ho ◽  
Wasco Wruck ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Amniotic Fluid ◽  
Stem Cell Marker ◽  
Human Mscs ◽  
Differentiation Potential ◽  
Cell Therapies ◽  
Kegg Pathways ◽  
Go Terms

Human amniotic fluid cells are immune-privileged with low immunogenicity and anti-inflammatory properties. They are able to self-renew, are highly proliferative, and have a broad differentiation potential, making them amenable for cell-based therapies. Amniotic fluid (AF) is routinely obtained via amniocentesis and contains heterogeneous populations of foetal-derived progenitor cells including mesenchymal stem cells (MSCs). In this study, we isolated human MSCs from AF (AF-MSCs) obtained during Caesarean sections (C-sections) and characterized them. These AF-MSCs showed typical MSC characteristics such as morphology,in vitrodifferentiation potential, surface marker expression, and secreted factors. Besides vimentin and the stem cell marker CD133, subpopulations of AF-MSCs expressed pluripotency-associated markers such as SSEA4, c-Kit, TRA-1-60, and TRA-1-81. The secretome and related gene ontology (GO) terms underline their immune modulatory properties. Furthermore, transcriptome analyses revealed similarities with native foetal bone marrow-derived MSCs. Significant KEGG pathways as well as GO terms are mostly related to immune function, embryonic skeletal system, and TGFβ-signalling. An AF-MSC-enriched gene set included putative AF-MSC markersPSG5,EMX-2, andEVR-3. In essence, C-section-derived AF-MSCs can be routinely obtained and are amenable for personalized cell therapies and disease modelling.

scholarly journals Effects of Donor Age, Long-Term Passage Culture, and Cryopreservation on Tonsil-Derived Mesenchymal Stem Cells

2015 ◽  
Vol 36 (1) ◽  
pp. 85-99 ◽  
Author(s):  
Jin-Sik Choi ◽  
Byung-Joo Lee ◽  
Hee-Young Park ◽  
Ji-Sun Song ◽  
Sung-Chan Shin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Surface Markers ◽  
Donor Age ◽  
Human Tonsil ◽  
Differentiation Potential ◽  
Morphological Differences ◽  
Proliferation Potential

Objectives: Human mesenchymal stem cells (MSCs) are efficacious in various cellular therapeutic applications and have been isolated from several tissues. Recent studies have reported that human tonsil tissue contains a new source of progenitor cells, potentially applicable for cell-based therapies. Information about the effects of donor age, long-term passage and cryopreservation are essential for clinical applications and cell-based therapies. Therefore, the authors investigated how the morphology, cell-surface markers, proliferation potential and differentiation capacity of tonsil-derived MSCs (T-MSCs) were affected by donor age, long-term passage, and cryopreservation. Materials and Methods: T-MSCs were isolated from tonsillar tissue of 20 patients undergoing tonsillectomy. Authors evaluated the effects of donor-age, long-term passage, and cryopreservation on the morphology, surface markers, proliferation potential and differentiation capacities of T-MSCs. Results: T-MSCs exhibited a fibroblast-like, spindle-shaped appearance. There were no significant morphological differences according to donor age, long-term passage or cryopreservation. T-MSCs isolated from donors of various ages were positive for markers CD90, CD44, and CD73, but negative for CD45, CD31, and HLA-DR. There were no significant differences in the expression of positive and negative surface markers as a function of donor age, long-term passage and cryopreservation. T-MSCs from different donor age groups showed similar proliferation potentials after passage 2. After long-term passage and cryopreservation, there were no significant morphological differences. Cryopreservation did not affect the proliferation potential of T-MSCs, but there was a significant decrease in the proliferation potential in long-term passage T-MSCs (passage 15). The effect of donor age, long-term passage and cryopreservation on the in vitro adipogenic, osteogenic, and chondrogenic differentiation potential of T-MSCs was not significant. Conclusion: The effect of donor age, long-term passage culture, and cryopreservation on T-MSC properties are negligible, except for the proliferation capacity of long-term cultured T-MSCs. Therefore, T-MSCs are considered to be promising MSCs that can be used as future alternative sources for autologous or allogenic MSCs.

scholarly journals Tenogenic differentiation of mesenchymal stem cells

2018 ◽  
Vol 3 (3) ◽  
pp. 2473011418S0030
Author(s):  
Seung Yeol Lee ◽  
Hyang Kim ◽  
Kyoung Min Lee
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tendon Repair ◽  
Human Tonsil ◽  
Differentiation Potential ◽  
Lineage Differentiation ◽  
Tenogenic Differentiation ◽  
Surface Marker Analysis

Category: Basic Sciences/Biologics Introduction/Purpose: Tendon repair has been a challenging issue for surgeons in treating. Although tissue engineering with mesenchymal stem cells (MSC) have been used for tendon repair in both in vivo and in vitro, the stem cells are obtained through invasive procedures, and there is usually a lack of adequate numbers for clinical use. The purpose of this study was to compare the potential of tri-lineage differentiation and to investigate the potential of tenogenic differentiation of human tonsil derived MSCs (T-MSCs), bone marrow derived MSCs (BM-MSCs), and adipose tissue derived MSCs (AD-MSCs). Methods: Each tissue was obtained from 8 patients. After isolation of MSCs, flow cytometry analysis was used to characterize the phenotypes of the MSCs. Differentiation capacity to adipo-, osteo-, and chondrocytes were induced by culturing each MSCs for 3 weeks in commercially available media. Each MSCs was treated with 5ng/ml and 10ng/ml of TGF-ß3 with vehicle control. Results: Immunophenotypic surface marker analysis of BM-MSC, AD-MSC, and TMSCs revealed that these MSCs expressed a typical MSCs. mRNA expression levels of the markers for tri-lineage differentiation were significantly lower in TMSC than other MSCs. The tenogenic transcription factor, scleraxis, showed a statistically significant increase in all MSCs differentiation groups except for the 7th day TMSC differentiation group (Figure). Gene expression of tenascin-C, an ECM glycoprotein, was specifically expressed in the T-MSC differentiation group at 14 days (Figure). Comparing the ratio of collagen 1 to collagen 3 genes, the BM-MSC showed a decrease in the ratio on days 3 and 7 unlike AD-MSCs and TMSCs. Only TMSC showed a significant increase in the ratio compared with other MSCs on the 14th day. Conclusion: The tonsil-MSC has low fat, bone and cartilage differentiation potential and has excellent tendon-specific differentiation potential, thus being highly useful as a tendon-tailored cell therapy agent.

scholarly journals Mesenchymal Stem Cells from Human Exfoliated Deciduous Teeth and the Orbicularis Oris Muscle: How Do They Behave When Exposed to a Proinflammatory Stimulus?

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Alessander Leyendecker Junior ◽  
Carla Cristina Gomes Pinheiro ◽  
Daniela Yukie Sakai Tanikawa ◽  
José Ricardo Muniz Ferreira ◽  
Mariane Tami Amano ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Deciduous Teeth ◽  
Differentiation Potential ◽  
Cell Therapies ◽  
Hla Dr ◽  
Before And After ◽  
Orbicularis Oris Muscle ◽  
Human Exfoliated Deciduous Teeth ◽  
Promising Type

Mesenchymal stem cells (MSCs) have been studied as a promising type of stem cell for use in cell therapies because of their ability to regulate the immune response. Although they are classically isolated from the bone marrow, many studies have sought to isolate MSCs from noninvasive sources. The objective of this study was to evaluate how MSCs isolated from the dental pulp of human exfoliated deciduous teeth (SHED) and fragments of the orbicularis oris muscle (OOMDSCs) behave when treated with an inflammatory IFN-γ stimulus, specifically regarding their proliferative, osteogenic, and immunomodulatory potentials. The results demonstrated that the proliferation of SHED and OOMDSCs was inhibited by the addition of IFN-γ to their culture medium and that treatment with IFN-γ at higher concentrations resulted in a greater inhibition of the proliferation of these cells than treatment with IFN-γ at lower concentrations. SHED and OOMDSCs maintained their osteogenic differentiation potential after stimulation with IFN-γ. Additionally, SHED and OOMDSCs have been shown to have low immunogenicity because they lack expression of HLA-DR and costimulatory molecules such as CD40, CD80, and CD86 before and after IFN-γ treatment. Last, SHED and OOMDSCs expressed the immunoregulatory molecule HLA-G, and the expression of this antigen increased after IFN-γ treatment. In particular, an increase in intracellular HLA-G expression was observed. The results obtained suggest that SHED and OOMDSCs lack immunogenicity and have immunomodulatory properties that are enhanced when they undergo inflammatory stimulation with IFN-γ, which opens new perspectives for the therapeutic use of these cells.

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