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3 pages, 199 KiB

Open AccessEditorial

Adipose-Derived Stromal/Stem Cells

by Patrick C. Baer

Cells 2020, 9(9), 1997; https://doi.org/10.3390/cells9091997 - 30 Aug 2020

Cited by 9 | Viewed by 2060

Abstract

Adipose tissue is a rich, ubiquitous, and easily accessible source for multipotent mesenchymal stromal/stem cells (MSCs), so-called adipose-derived stromal/stem cells (ASCs) [...] Full article

(This article belongs to the Special Issue Adipose-Derived Stromal/Stem Cells)

Research

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11 pages, 2049 KiB

Open AccessCommunication

Tracking of Infused Mesenchymal Stem Cells in Injured Pulmonary Tissue in Atm-Deficient Mice

by Patrick C. Baer, Julia Sann, Ruth Pia Duecker, Evelyn Ullrich, Helmut Geiger, Peter Bader, Stefan Zielen and Ralf Schubert

Cells 2020, 9(6), 1444; https://doi.org/10.3390/cells9061444 - 10 Jun 2020

Cited by 6 | Viewed by 2460

Abstract

Pulmonary failure is the main cause of morbidity and mortality in the human chromosomal instability syndrome Ataxia-telangiectasia (A-T). Major phenotypes include recurrent respiratory tract infections and bronchiectasis, aspiration, respiratory muscle abnormalities, interstitial lung disease, and pulmonary fibrosis. At present, no effective pulmonary therapy [...] Read more.

Pulmonary failure is the main cause of morbidity and mortality in the human chromosomal instability syndrome Ataxia-telangiectasia (A-T). Major phenotypes include recurrent respiratory tract infections and bronchiectasis, aspiration, respiratory muscle abnormalities, interstitial lung disease, and pulmonary fibrosis. At present, no effective pulmonary therapy for A-T exists. Cell therapy using adipose-derived mesenchymal stromal/stem cells (ASCs) might be a promising approach for tissue regeneration. The aim of the present project was to investigate whether ASCs migrate into the injured lung parenchyma of Atm-deficient mice as an indication of incipient tissue damage during A-T. Therefore, ASCs isolated from luciferase transgenic mice (mASCs) were intravenously transplanted into Atm-deficient and wild-type mice. Retention kinetics of the cells were monitored using in vivo bioluminescence imaging (BLI) and completed by subsequent verification using quantitative real-time polymerase chain reaction (qRT-PCR). The in vivo imaging and the qPCR results demonstrated migration accompanied by a significantly longer retention time of transplanted mASCs in the lung parenchyma of Atm-deficient mice compared to wild type mice. In conclusion, our study suggests incipient damage in the lung parenchyma of Atm-deficient mice. In addition, our data further demonstrate that a combination of luciferase-based PCR together with BLI is a pivotal tool for tracking mASCs after transplantation in models of inflammatory lung diseases such as A-T. Full article

(This article belongs to the Special Issue Adipose-Derived Stromal/Stem Cells)

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14 pages, 25219 KiB

Open AccessArticle

Murine Mesenchymal Stromal Cells Retain Biased Differentiation Plasticity Towards Their Tissue of Origin

by Ting Ting Ng, Kylie Hin-Man Mak, Christian Popp and Ray Kit Ng

Cells 2020, 9(3), 756; https://doi.org/10.3390/cells9030756 - 19 Mar 2020

Cited by 8 | Viewed by 7161

Abstract

Mesenchymal stromal/stem cells (MSCs) reside in many human tissues and comprise a heterogeneous population of cells with self-renewal and multi-lineage differentiation potential, making them useful in regenerative medicine. It remains inconclusive whether MSCs isolated from different tissue sources exhibit variations in biological features. [...] Read more.

Mesenchymal stromal/stem cells (MSCs) reside in many human tissues and comprise a heterogeneous population of cells with self-renewal and multi-lineage differentiation potential, making them useful in regenerative medicine. It remains inconclusive whether MSCs isolated from different tissue sources exhibit variations in biological features. In this study, we derived MSCs from adipose tissue (AT-MSC) and compact bone (CB-MSC). We found that early passage of MSCs was readily expandable ex vivo, whereas the prolonged culture of MSCs showed alteration of cell morphology to fibroblastoid and reduced proliferation. CB-MSCs and AT-MSCs at passage 3 were CD29⁺, CD44⁺, CD105⁺, CD106⁺, and Sca-1⁺; however, passage 7 MSCs showed a reduction of MSC markers, indicating loss of stem cell population after prolonged culturing. Strikingly, CB-MSC was found more efficient at undergoing osteogenic differentiation, while AT-MSC was more efficient to differentiate into adipocytes. The biased differentiation pattern of MSCs from adipogenic or osteogenic tissue source was accompanied by preferential expression of the corresponding lineage marker genes. Interestingly, CB-MSCs treated with DNA demethylation agent 5-azacytidine showed enhanced osteogenic and adipogenic differentiation, whereas the treated AT-MSCs are less competent to differentiate. Our results suggest that the epigenetic state of MSCs is associated with the biased differentiation plasticity towards its tissue of origin, proposing a mechanism related to the retention of epigenetic memory. These findings facilitate the selection of optimal tissue sources of MSCs and the ex vivo expansion period for therapeutic applications. Full article

(This article belongs to the Special Issue Adipose-Derived Stromal/Stem Cells)

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26 pages, 3052 KiB

Open AccessArticle

Valproic Acid Promotes Early Neural Differentiation in Adult Mesenchymal Stem Cells Through Protein Signalling Pathways

by Jerran Santos, Thibaut Hubert and Bruce K Milthorpe

Cells 2020, 9(3), 619; https://doi.org/10.3390/cells9030619 - 4 Mar 2020

Cited by 23 | Viewed by 4353

Abstract

Regenerative medicine is a rapidly expanding area in research and clinical applications. Therapies involving the use of small molecule chemicals aim to simplify the creation of specific drugs for clinical applications. Adult mesenchymal stem cells have recently shown the capacity to differentiate into [...] Read more.

Regenerative medicine is a rapidly expanding area in research and clinical applications. Therapies involving the use of small molecule chemicals aim to simplify the creation of specific drugs for clinical applications. Adult mesenchymal stem cells have recently shown the capacity to differentiate into several cell types applicable for regenerative medicine (specifically neural cells, using chemicals). Valproic acid was an ideal candidate due to its clinical stability. It has been implicated in the induction of neural differentiation; however, the mechanism and the downstream events were not known. In this study, we showed that using valproic acid on adult mesenchymal stem cells induced neural differentiation within 24 h by upregulating the expression of suppressor of cytokine signaling 5 (SOCS5) and Fibroblast growth factor 21 (FGF21), without increasing the potential death rate of the cells. Through this, the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway is downregulated, and the mitogen-activated protein kinase (MAPK) cascade is activated. The bioinformatics analyses revealed the expression of several neuro-specific proteins as well as a range of functional and structural proteins involved in the formation and development of the neural cells. Full article

(This article belongs to the Special Issue Adipose-Derived Stromal/Stem Cells)

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19 pages, 6504 KiB

Open AccessArticle

Permanent Pro-Tumorigenic Shift in Adipose Tissue-Derived Mesenchymal Stromal Cells Induced by Breast Malignancy

by Jana Plava, Marina Cihova, Monika Burikova, Martin Bohac, Marian Adamkov, Slavka Drahosova, Dominika Rusnakova, Daniel Pindak, Marian Karaba, Jan Simo, Michal Mego, Lubos Danisovic, Lucia Kucerova and Svetlana Miklikova

Cells 2020, 9(2), 480; https://doi.org/10.3390/cells9020480 - 19 Feb 2020

Cited by 20 | Viewed by 4274

Abstract

During cancer progression, breast tumor cells interact with adjacent adipose tissue, which has been shown to be engaged in cancer aggressiveness. However, the tumor-directed changes in adipose tissue-resident stromal cells affected by the tumor–stroma communication are still poorly understood. The acquired changes might [...] Read more.

During cancer progression, breast tumor cells interact with adjacent adipose tissue, which has been shown to be engaged in cancer aggressiveness. However, the tumor-directed changes in adipose tissue-resident stromal cells affected by the tumor–stroma communication are still poorly understood. The acquired changes might remain in the tissue even after tumor removal and may contribute to tumor relapse. We investigated functional properties (migratory capacity, expression and secretion profile) of mesenchymal stromal cells isolated from healthy (n = 9) and tumor-distant breast adipose tissue (n = 32). Cancer patient-derived mesenchymal stromal cells (MSCs) (MSC-CA) exhibited a significantly disarranged secretion profile and proliferation potential. Co-culture with MDA-MB-231, T47D and JIMT-1, representing different subtypes of breast cancer, was used to analyze the effect of MSCs on proliferation, invasion and tumorigenicity. The MSC-CA enhanced tumorigenicity and altered xenograft composition in immunodeficient mice. Histological analysis revealed collective cell invasion with a specific invasive front of EMT-positive tumor cells as well as invasion of cancer cells to the nerve-surrounding space. This study identifies that adipose tissue-derived mesenchymal stromal cells are primed and permanently altered by tumor presence in breast tissue and have the potential to increase tumor cell invasive ability through the activation of epithelial-to-mesenchymal transition in tumor cells. Full article

(This article belongs to the Special Issue Adipose-Derived Stromal/Stem Cells)

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15 pages, 1425 KiB

Open AccessArticle

The Phenotype and Secretory Activity of Adipose-Derived Mesenchymal Stem Cells (ASCs) of Patients with Rheumatic Diseases

by Ewa Kuca-Warnawin, Urszula Skalska, Iwona Janicka, Urszula Musiałowicz, Krzysztof Bonek, Piotr Głuszko, Piotr Szczęsny, Marzena Olesińska and Ewa Kontny

Cells 2019, 8(12), 1659; https://doi.org/10.3390/cells8121659 - 17 Dec 2019

Cited by 20 | Viewed by 4017

Abstract

Mesenchymal stem/stromal cells (MSCs) have immunosuppressive and regenerative properties. Adipose tissue is an alternative source of MSCs, named adipose-derived mesenchymal stem cells (ASCs). Because the biology of ASCs in rheumatic diseases (RD) is poorly understood, we performed a basic characterization of RD/ASCs. The [...] Read more.

Mesenchymal stem/stromal cells (MSCs) have immunosuppressive and regenerative properties. Adipose tissue is an alternative source of MSCs, named adipose-derived mesenchymal stem cells (ASCs). Because the biology of ASCs in rheumatic diseases (RD) is poorly understood, we performed a basic characterization of RD/ASCs. The phenotype and expression of adhesion molecules (intracellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1) on commercially available healthy donors (HD), ASC lines (n = 5) and on ASCs isolated from patients with systemic lupus erythematosus (SLE, n = 16), systemic sclerosis (SSc, n = 17) and ankylosing spondylitis (AS, n = 16) were analyzed by flow cytometry. The secretion of immunomodulatory factors by untreated and cytokine-treated ASCs was measured by ELISA. RD/ASCs have reduced basal levels of CD90 and ICAM-1 expression, correlated with interleukin (IL)-6 and transforming growth factor (TGF)-β1 release, respectively. Compared with HD/ASCs, untreated and tumour necrosis factor (TNF) + interferon (IFN)-γ (TI)-treated RD/ASCs produced similar amounts of prostaglandin E2 (PGE₂), IL-6, leukemia inhibiting factor (LIF), and TGF-β1, more IL-1Ra, soluble human leukocyte antigen G (sHLA-G) and tumor necrosis factor-inducible gene (TSG)-6, but less kynurenines and galectin-3. Basal secretion of galectin-3 was inversely correlated with the patient’s erythrocyte sedimentation rate (ESR) value. IFN-α and IL-23 slightly raised galectin-3 release from SLE/ASCs and AS/ASCs, respectively. TGF-β1 up-regulated PGE₂ secretion by SSc/ASCs. In conclusion, RD/ASCs are characterized by low basal levels of CD90 and ICAM-1 expression, upregulated secretion of IL-1Ra, TSG-6 and sHLA-G, but impaired release of kynurenines and galectin-3. These abnormalities may modify biological activities of RD/ASCs. Full article

(This article belongs to the Special Issue Adipose-Derived Stromal/Stem Cells)

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16 pages, 3508 KiB

Open AccessFeature PaperArticle

Natural Histogel-Based Bio-Scaffolds for Sustaining Angiogenesis in Beige Adipose Tissue

by Margherita Di Somma, Wandert Schaafsma, Elisabetta Grillo, Maria Vliora, Eleni Dakou, Michela Corsini, Cosetta Ravelli, Roberto Ronca, Paraskevi Sakellariou, Jef Vanparijs, Begona Castro and Stefania Mitola

Cells 2019, 8(11), 1457; https://doi.org/10.3390/cells8111457 - 18 Nov 2019

Cited by 12 | Viewed by 4227

Abstract

In the treatment of obesity and its related disorders, one of the measures adopted is weight reduction by controlling nutrition and increasing physical activity. A valid alternative to restore the physiological function of the human body could be the increase of energy consumption [...] Read more.

In the treatment of obesity and its related disorders, one of the measures adopted is weight reduction by controlling nutrition and increasing physical activity. A valid alternative to restore the physiological function of the human body could be the increase of energy consumption by inducing the browning of adipose tissue. To this purpose, we tested the ability of Histogel, a natural mixture of glycosaminoglycans isolated from animal Wharton jelly, to sustain the differentiation of adipose derived mesenchymal cells (ADSCs) into brown-like cells expressing UCP-1. Differentiated cells show a higher energy metabolism compared to undifferentiated mesenchymal cells. Furthermore, Histogel acts as a pro-angiogenic matrix, induces endothelial cell proliferation and sprouting in a three-dimensional gel in vitro, and stimulates neovascularization when applied in vivo on top of the chicken embryo chorioallantoic membrane or injected subcutaneously in mice. In addition to the pro-angiogenic activity of Histogel, also the ADSC derived beige cells contribute to activating endothelial cells. These data led us to propose Histogel as a promising scaffold for the modulation of the thermogenic behavior of adipose tissue. Indeed, Histogel simultaneously supports the acquisition of brown tissue markers and activates the vasculature process necessary for the correct function of the thermogenic tissue. Thus, Histogel represents a valid candidate for the development of bioscaffolds to increase the amount of brown adipose tissue in patients with metabolic disorders. Full article

(This article belongs to the Special Issue Adipose-Derived Stromal/Stem Cells)

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17 pages, 4131 KiB

Open AccessFeature PaperArticle

Isolation, Characterization, Differentiation and Immunomodulatory Capacity of Mesenchymal Stromal/Stem Cells from Human Perirenal Adipose Tissue

by Patrick C. Baer, Benjamin Koch, Elena Hickmann, Ralf Schubert, Jindrich Cinatl, Jr., Ingeborg A. Hauser and Helmut Geiger

Cells 2019, 8(11), 1346; https://doi.org/10.3390/cells8111346 - 29 Oct 2019

Cited by 27 | Viewed by 3718

Abstract

Mesenchymal stromal/stem cells (MSCs) are immature multipotent cells, which represent a rare population in the perivascular niche within nearly all tissues. The most abundant source to isolate MSCs is adipose tissue. Currently, perirenal adipose tissue is rarely described as the source of MSCs. [...] Read more.

Mesenchymal stromal/stem cells (MSCs) are immature multipotent cells, which represent a rare population in the perivascular niche within nearly all tissues. The most abundant source to isolate MSCs is adipose tissue. Currently, perirenal adipose tissue is rarely described as the source of MSCs. MSCs were isolated from perirenal adipose tissue (prASCs) from patients undergoing tumor nephrectomies, cultured and characterized by flow cytometry and their differentiation potential into adipocytes, chondrocytes, osteoblasts and epithelial cells. Furthermore, prASCs were stimulated with lipopolysaccharide (LPS), lipoteichoic acid (LTA) or a mixture of cytokines (cytomix). In addition, prASC susceptibility to human cytomegalovirus (HCMV) was investigated. The expression of inflammatory readouts was estimated by qPCR and immunoassay. HCMV infection was analyzed by qPCR and immunostaining. Characterization of cultured prASCs shows the cells meet the criteria of MSCs and prASCs can undergo trilineage differentiation. Cultured prASCs can be induced to differentiate into epithelial cells, shown by cytokeratin 18 expression. Stimulation of prASCs with LPS or cytomix suggests the cells are capable of initiating an inflammation-like response upon stimulation with LPS or cytokines, whereas, LTA did not induce a significant effect on the readouts (ICAM-1, IL-6, TNFα, MCP-1 mRNA and IL-6 protein). HCMV broadly infects prASCs, showing a viral load dependent cytopathological effect (CPE). Our current study summarizes the isolation and culture of prASCs, clearly characterizes the cells, and demonstrates their immunomodulatory potential and high permissiveness for HCMV. Full article

(This article belongs to the Special Issue Adipose-Derived Stromal/Stem Cells)

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23 pages, 9489 KiB

Open AccessArticle

Subcutaneous and Visceral Adipose-Derived Mesenchymal Stem Cells: Commonality and Diversity

by Andreas Ritter, Alexandra Friemel, Susanne Roth, Nina-Naomi Kreis, Samira Catharina Hoock, Babek Khan Safdar, Kyra Fischer, Charlotte Möllmann, Christine Solbach, Frank Louwen and Juping Yuan

Cells 2019, 8(10), 1288; https://doi.org/10.3390/cells8101288 - 21 Oct 2019

Cited by 41 | Viewed by 4239

Abstract

Adipose-derived mesenchymal stem cells (ASCs) are considered to be a useful tool for regenerative medicine, owing to their capabilities in differentiation, self-renewal, and immunomodulation. These cells have become a focus in the clinical setting due to their abundance and easy isolation. However, ASCs [...] Read more.

Adipose-derived mesenchymal stem cells (ASCs) are considered to be a useful tool for regenerative medicine, owing to their capabilities in differentiation, self-renewal, and immunomodulation. These cells have become a focus in the clinical setting due to their abundance and easy isolation. However, ASCs from different depots are not well characterized. Here, we analyzed the functional similarities and differences of subcutaneous and visceral ASCs. Subcutaneous ASCs have an extraordinarily directed mode of motility and a highly dynamic focal adhesion turnover, even though they share similar surface markers, whereas visceral ASCs move in an undirected random pattern with more stable focal adhesions. Visceral ASCs have a higher potential to differentiate into adipogenic and osteogenic cells when compared to subcutaneous ASCs. In line with these observations, visceral ASCs demonstrate a more active sonic hedgehog pathway that is linked to a high expression of cilia/differentiation related genes. Moreover, visceral ASCs secrete higher levels of inflammatory cytokines interleukin-6, interleukin-8, and tumor necrosis factor α relative to subcutaneous ASCs. These findings highlight, that both ASC subpopulations share multiple cellular features, but significantly differ in their functions. The functional diversity of ASCs depends on their origin, cellular context and surrounding microenvironment within adipose tissues. The data provide important insight into the biology of ASCs, which might be useful in choosing the adequate ASC subpopulation for regenerative therapies. Full article

(This article belongs to the Special Issue Adipose-Derived Stromal/Stem Cells)

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12 pages, 1549 KiB

Open AccessArticle

Differences between the Proliferative Effects of Human Platelet Lysate and Fetal Bovine Serum on Human Adipose-Derived Stem Cells

by Natsuko Kakudo, Naoki Morimoto, Yuanyuan Ma and Kenji Kusumoto

Cells 2019, 8(10), 1218; https://doi.org/10.3390/cells8101218 - 8 Oct 2019

Cited by 22 | Viewed by 4231

Abstract

Background: Recently, human adipose-derived stem cells (hASCs) were discovered in the human subcutaneous adipose tissue. PLTMax Human Platelet Lysate (PLTMax), a supplement refined from human platelets, has been reported to have proliferative effects on bone marrow mesenchymal stem cells. The proliferative effects of [...] Read more.

Background: Recently, human adipose-derived stem cells (hASCs) were discovered in the human subcutaneous adipose tissue. PLTMax Human Platelet Lysate (PLTMax), a supplement refined from human platelets, has been reported to have proliferative effects on bone marrow mesenchymal stem cells. The proliferative effects of PLTMax on ASCs were investigated in this study. Methods: The ASCs in DMEM (serum-free), DMEM+PLTMax (1%, 2%, 5%, and 10%), and DMEM+FBS (10%) were cultivated for two, five, and seven days. The cell growth rate was examined, BrdU incorporation, and the cell cycle and Ki-67 immunostaining were performed. The cell growth rate was investigated when each inhibitor (PD98059, SP600125, SB203580, and LY294002) was added and phosphorylation of ERK1/2, JNK, p38, and Akt were examined by western blotting. The cell surface marker of hASCs was also analyzed. Results: The cells in the PLTMax (5%) group showed significantly more proliferation compared to the cells in control (serum-free) and FBS (10%) groups, and a significant increase in the number of cells in the S phase and G2/M phase. The number of Ki-67 positive cells increased significantly in the DMEM+ PLTMax (5%) and the FBS (10%) groups. The addition of inhibitors PD98059, SP600125, SB203580, and LY294002 decreased the proliferative effects of PLTMax on ASCs. Phosphorylation of ERK1/2, JNK, p38, and Akt was observed in both the PLTMax (5%) and the FBS (10%) groups. Conclusions: For human adipose stem cells, 5% PLTMax was the optimum concentration, which showed a significantly higher proliferative effect than 10% FBS. PLTMax is a useful medium additive, which can substitute FBS. The proliferative effects of PLTMax are suggested to function via multiple signaling pathways, similar to FBS. Full article

(This article belongs to the Special Issue Adipose-Derived Stromal/Stem Cells)

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14 pages, 1178 KiB

Open AccessArticle

Differences in the Emission of Volatile Organic Compounds (VOCs) between Non-Differentiating and Adipogenically Differentiating Mesenchymal Stromal/Stem Cells from Human Adipose Tissue

by Ann-Christin Klemenz, Juliane Meyer, Katharina Ekat, Julia Bartels, Selina Traxler, Jochen K. Schubert, Günter Kamp, Wolfram Miekisch and Kirsten Peters

Cells 2019, 8(7), 697; https://doi.org/10.3390/cells8070697 - 10 Jul 2019

Cited by 20 | Viewed by 5927

Abstract

Metabolic characterization of human adipose tissue-derived mesenchymal stromal/stem cells (ASCs) is of importance in stem cell research. The monitoring of the cell status often requires cell destruction. An analysis of volatile organic compounds (VOCs) in the headspace above cell cultures might be a [...] Read more.

Metabolic characterization of human adipose tissue-derived mesenchymal stromal/stem cells (ASCs) is of importance in stem cell research. The monitoring of the cell status often requires cell destruction. An analysis of volatile organic compounds (VOCs) in the headspace above cell cultures might be a noninvasive and nondestructive alternative to in vitro analysis. Furthermore, VOC analyses permit new insight into cellular metabolism due to their view on volatile compounds. Therefore, the aim of our study was to compare VOC profiles in the headspace above nondifferentiating and adipogenically differentiating ASCs. To this end, ASCs were cultivated under nondifferentiating and adipogenically differentiating conditions for up to 21 days. At different time points the headspace samples were preconcentrated by needle trap micro extraction and analyzed by gas chromatography/mass spectrometry. Adipogenic differentiation was assessed at equivalent time points. Altogether the emissions of 11 VOCs showed relevant changes and were analyzed in more detail. A few of these VOCs, among them acetaldehyde, were significantly different in the headspace of adipogenically differentiating ASCs and appeared to be linked to metabolic processes. Furthermore, our data indicate that VOC headspace analysis might be a suitable, noninvasive tool for the metabolic monitoring of (mesenchymal stem) cells in vitro. Full article

(This article belongs to the Special Issue Adipose-Derived Stromal/Stem Cells)

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13 pages, 4415 KiB

Open AccessArticle

Collagen I Promotes Adipocytogenesis in Adipose-Derived Stem Cells In Vitro

by Nadja Zöller, Sarah Schreiner, Laura Petry, Stephanie Hoffmann, Katja Steinhorst, Johannes Kleemann, Manuel Jäger, Roland Kaufmann, Markus Meissner and Stefan Kippenberger

Cells 2019, 8(4), 302; https://doi.org/10.3390/cells8040302 - 1 Apr 2019

Cited by 18 | Viewed by 4728

Abstract

A hallmark of ageing is the redistribution of body fat. Particularly, subcutaneous fat decreases paralleled by a decrease of skin collagen I are typical for age-related skin atrophy. In this paper, we hypothesize that collagen I may be a relevant molecule stimulating the [...] Read more.

A hallmark of ageing is the redistribution of body fat. Particularly, subcutaneous fat decreases paralleled by a decrease of skin collagen I are typical for age-related skin atrophy. In this paper, we hypothesize that collagen I may be a relevant molecule stimulating the differentiation of adipose-derived stem cells (ASCs) into adipocytes augmenting subcutaneous fat. In this context lipogenesis, adiponectin, and collagen I receptor expression were determined. Freshly isolated ASCs were characterized by stemness-associated surface markers by FACS analysis and then transdifferentiated into adipocytes by specific medium supplements. Lipogenesis was evaluated using Nile Red staining and documented by fluorescence microscopy or quantitatively measured by using a multiwell spectrofluorometer. Expression of adiponectin was measured by real-time RT-PCR and in cell-free supernatants by ELISA, and expression of collagen I receptors was observed by western blot analysis. It was found that supports coated with collagen I promote cell adhesion and lipogenesis of ASCs. Interestingly, a reverse correlation to adiponectin expression was observed. Moreover, we found upregulation of the collagen receptor, discoidin domain-containing receptor 2; receptors of the integrin family were absent or downregulated. These findings indicate that collagen I is able to modulate lipogenesis and adiponectin expression and therefore may contribute to metabolic dysfunctions associated with ageing. Full article

(This article belongs to the Special Issue Adipose-Derived Stromal/Stem Cells)

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20 pages, 3900 KiB

Open AccessArticle

Metformin Increases Proliferative Activity and Viability of Multipotent Stromal Stem Cells Isolated from Adipose Tissue Derived from Horses with Equine Metabolic Syndrome

by Agnieszka Smieszek, Katarzyna Kornicka, Jolanta Szłapka-Kosarzewska, Peter Androvic, Lukas Valihrach, Lucie Langerova, Eva Rohlova, Mikael Kubista and Krzysztof Marycz

Cells 2019, 8(2), 80; https://doi.org/10.3390/cells8020080 - 22 Jan 2019

Cited by 23 | Viewed by 5406

Abstract

In this study, we investigated the influence of metformin (MF) on proliferation and viability of adipose-derived stromal cells isolated from horses (EqASCs). We determined the effect of metformin on cell metabolism in terms of mitochondrial metabolism and oxidative status. Our purpose was to [...] Read more.

In this study, we investigated the influence of metformin (MF) on proliferation and viability of adipose-derived stromal cells isolated from horses (EqASCs). We determined the effect of metformin on cell metabolism in terms of mitochondrial metabolism and oxidative status. Our purpose was to evaluate the metformin effect on cells derived from healthy horses (EqASC_HE) and individuals affected by equine metabolic syndrome (EqASC_EMS). The cells were treated with 0.5 μM MF for 72 h. The proliferative activity was evaluated based on the measurement of BrdU incorporation during DNA synthesis, as well as population doubling time rate (PDT) and distribution of EqASCs in the cell cycle. The influence of metformin on EqASC viability was determined in relation to apoptosis profile, mitochondrial membrane potential, oxidative stress markers and BAX/BCL-2 mRNA ratio. Further, we were interested in possibility of metformin affecting the Wnt3a signalling pathway and, thus, we determined mRNA and protein level of WNT3A and β-catenin. Finally, using a two-tailed RT-qPCR method, we investigated the expression of miR-16-5p, miR-21-5p, miR-29a-3p, miR-140-3p and miR-145-5p. Obtained results indicate pro-proliferative and anti-apoptotic effects of metformin on EqASCs. In this study, MF significantly improved proliferation of EqASCs, which manifested in increased synthesis of DNA and lowered PDT value. Additionally, metformin improved metabolism and viability of cells, which correlated with higher mitochondrial membrane potential, reduced apoptosis and increased WNT3A/β-catenin expression. Metformin modulates the miRNA expression differently in EqASC_HE and EqASC_EMS. Metformin may be used as a preconditioning agent which stimulates proliferative activity and viability of EqASCs. Full article

(This article belongs to the Special Issue Adipose-Derived Stromal/Stem Cells)

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15 pages, 3587 KiB

Open AccessArticle

Assessment of the Immunosuppressive Potential of INF-γ Licensed Adipose Mesenchymal Stem Cells, Their Secretome and Extracellular Vesicles

by Teresa Raquel Tavares Serejo, Amandda Évelin Silva-Carvalho, Luma Dayane de Carvalho Filiú Braga, Francisco de Assis Rocha Neves, Rinaldo Wellerson Pereira, Juliana Lott de Carvalho and Felipe Saldanha-Araujo

Cells 2019, 8(1), 22; https://doi.org/10.3390/cells8010022 - 5 Jan 2019

Cited by 55 | Viewed by 5483

Abstract

There is an active search for the ideal strategy to potentialize the effects of Mesenchymal Stem-Cells (MSCs) over the immune system. Also, part of the scientific community is seeking to elucidate the therapeutic potential of MSCs secretome and its extracellular vesicles (EVs), in [...] Read more.

There is an active search for the ideal strategy to potentialize the effects of Mesenchymal Stem-Cells (MSCs) over the immune system. Also, part of the scientific community is seeking to elucidate the therapeutic potential of MSCs secretome and its extracellular vesicles (EVs), in order to avoid the complexity of a cellular therapy. Here, we investigate the effects of human adipose MSCs (AMSCs) licensing with INF-γ and TLR3 agonist over AMSCs proliferation, migration, as well as the immunomodulatory function. Furthermore, we evaluated how the licensing of AMSCs affected the immunomodulatory function of AMSC derived-secretome, including their EVs. INF-γ licensed-AMSCs presented an elevated expression of indoleamine 2,3-dioxygenase (IDO), accompanied by increased ICAM-1, as well as a higher immunosuppressive potential, compared to unlicensed AMSCs. Interestingly, the conditioned medium obtained from INF-γ licensed-AMSCs also revealed a slightly superior immunosuppressive potential, compared to other licensing strategies. Therefore, unlicensed and INF-γ licensed-AMSCs groups were used to isolate EVs. Interestingly, EVs isolated from both groups displayed similar capacity to inhibit T-cell proliferation. EVs isolated from both groups shared similar TGF-β and Galectin-1 mRNA content but only EVs derived from INF-γ licensed-AMSCs expressed IDO mRNA. In summary, we demonstrated that INF-γ licensing of AMSCs provides an immunosuppressive advantage both from a cell-cell contact-dependent perspective, as well as in a cell-free context. Interestingly, EVs derived from unlicensed and INF-γ licensed-AMSCs have similar ability to control activated T-cell proliferation. These results contribute towards the development of new strategies to control the immune response based on AMSCs or their derived products. Full article

(This article belongs to the Special Issue Adipose-Derived Stromal/Stem Cells)

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22 pages, 17012 KiB

Open AccessArticle

Stem Cells Derived from Lipoma and Adipose Tissue—Similar Mesenchymal Phenotype but Different Differentiation Capacity Governed by Distinct Molecular Signature

by Sanja Stojanović, Stevo Najman and Aleksandra Korać

Cells 2018, 7(12), 260; https://doi.org/10.3390/cells7120260 - 8 Dec 2018

Cited by 16 | Viewed by 6473

Abstract

Lipomas are benign adipose tissue tumors of unknown etiology, which can vary in size, number, body localization and cell populations within the tissue. Lipoma-derived stem cells (LDSCs) are proposed as a potential tool in regenerative medicine and tissue engineering due to their similar [...] Read more.

Lipomas are benign adipose tissue tumors of unknown etiology, which can vary in size, number, body localization and cell populations within the tissue. Lipoma-derived stem cells (LDSCs) are proposed as a potential tool in regenerative medicine and tissue engineering due to their similar characteristics with adipose-derived stem cells (ADSCs) reported so far. Our study is among the first giving detailed insights into the molecular signature and differences in the differentiation capacity of LDSCs in vitro compared to ADSCs. Mesenchymal stem cell phenotype was analyzed by gene expression and flow cytometric analysis of stem cell markers. Adipogenesis and osteogenesis were analyzed by microscopic analysis, cytochemical and immunocytochemical staining, gene and protein expression analyses. We showed that both LDSCs and ADSCs were mesenchymal stem cells with similar phenotype and stemness state but different molecular basis for potential differentiation. Adipogenesis-related genes expression pattern and presence of more mature adipocytes in ADSCs than in LDSCs after 21 days of adipogenic differentiation, indicated that differentiation capacity of LDSCs was significantly lower compared to ADSCs. Analysis of osteogenesis-related markers after 16 days of osteogenic differentiation revealed that both types of cells had characteristic osteoblast-like phenotype, but were at different stages of osteogenesis. Differences observed between LDSCs and ADSCs are probably due to the distinct molecular signature and their commitment in the tissue that governs their different capacity and fate during adipogenic and osteogenic induction in vitro despite their similar mesenchymal phenotype. Full article

(This article belongs to the Special Issue Adipose-Derived Stromal/Stem Cells)

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Review

Jump to: Editorial, Research, Other

13 pages, 755 KiB

Open AccessReview

Spheroid Culture System Methods and Applications for Mesenchymal Stem Cells

by Na-Eun Ryu, Soo-Hong Lee and Hansoo Park

Cells 2019, 8(12), 1620; https://doi.org/10.3390/cells8121620 - 12 Dec 2019

Cited by 322 | Viewed by 22878

Abstract

Owing to the importance of stem cell culture systems in clinical applications, researchers have extensively studied them to optimize the culture conditions and increase efficiency of cell culture. A spheroid culture system provides a similar physicochemical environment in vivo by facilitating cell–cell and [...] Read more.

Owing to the importance of stem cell culture systems in clinical applications, researchers have extensively studied them to optimize the culture conditions and increase efficiency of cell culture. A spheroid culture system provides a similar physicochemical environment in vivo by facilitating cell–cell and cell–matrix interaction to overcome the limitations of traditional monolayer cell culture. In suspension culture, aggregates of adjacent cells form a spheroid shape having wide utility in tumor and cancer research, therapeutic transplantation, drug screening, and clinical study, as well as organic culture. There are various spheroid culture methods such as hanging drop, gel embedding, magnetic levitation, and spinner culture. Lately, efforts are being made to apply the spheroid culture system to the study of drug delivery platforms and co-cultures, and to regulate differentiation and pluripotency. To study spheroid cell culture, various kinds of biomaterials are used as building forms of hydrogel, film, particle, and bead, depending upon the requirement. However, spheroid cell culture system has limitations such as hypoxia and necrosis in the spheroid core. In addition, studies should focus on methods to dissociate cells from spheroid into single cells. Full article

(This article belongs to the Special Issue Adipose-Derived Stromal/Stem Cells)

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Human Platelet Lysate as a Functional Substitute for Fetal Bovine Serum in the Culture of Human Adipose Derived Stromal/Stem Cells

by Mathew Cowper, Trivia Frazier, Xiying Wu, J. Lowry Curley, Michelle H. Ma, Omair A. Mohiuddin, Marilyn Dietrich, Michelle McCarthy, Joanna Bukowska and Jeffrey M. Gimble

Cells 2019, 8(7), 724; https://doi.org/10.3390/cells8070724 - 15 Jul 2019

Cited by 35 | Viewed by 4992

Abstract

Introduction: Adipose derived stromal/stem cells (ASCs) hold potential as cell therapeutics for a wide range of disease states; however, many expansion protocols rely on the use of fetal bovine serum (FBS) as a cell culture nutrient supplement. The current study explores the substitution [...] Read more.

Introduction: Adipose derived stromal/stem cells (ASCs) hold potential as cell therapeutics for a wide range of disease states; however, many expansion protocols rely on the use of fetal bovine serum (FBS) as a cell culture nutrient supplement. The current study explores the substitution of lysates from expired human platelets (HPLs) as an FBS substitute. Methods: Expired human platelets from an authorized blood center were lysed by freeze/thawing and used to examine human ASCs with respect to proliferation using hematocytometer cell counts, colony forming unit-fibroblast (CFU-F) frequency, surface immunophenotype by flow cytometry, and tri-lineage (adipocyte, chondrocyte, osteoblast) differentiation potential by histochemical staining. Results: The proliferation assays demonstrated that HPLs supported ASC proliferation in a concentration dependent manner, reaching levels that exceeded that observed in the presence of 10% FBS. The concentration of 0.75% HPLs was equivalent to 10% FBS when utilized in cell culture media with respect to proliferation, immunophenotype, and CFU-F frequency. When added to osteogenic, adipogenic, and chondrogenic differentiation media, both supplements showed appropriate differentiation by staining. Conclusion: HPLs is an effective substitute for FBS in the culture, expansion and differentiation of human ASCs suitable for pre-clinical studies; however, additional assays and analyses will be necessary to validate HPLs for clinical applications and regulatory approval. Full article

(This article belongs to the Special Issue Adipose-Derived Stromal/Stem Cells)

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