scholarly journals IL-17A and TNF Modulate Normal Human Spinal Entheseal Bone and Soft Tissue Mesenchymal Stem Cell Osteogenesis, Adipogenesis, and Stromal Function

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 341
Author(s):  
Tobias Russell ◽  
Abdulla Watad ◽  
Charlie Bridgewood ◽  
Hannah Rowe ◽  
Almas Khan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Soft Tissue ◽  
Mesenchymal Stem Cell ◽  
Immune Cell ◽  
Adipogenic Differentiation ◽  
Fine Tuning ◽  
Peroxisome Proliferator ◽  
Fatty Acid Binding ◽  
Recruitment Methods

Objective: The spondylarthritides (SpA) are intimately linked to new bone formation and IL-17A and TNF pathways. We investigated spinal soft tissue and bone mesenchymal stem cell (MSC) responses to IL-17A and TNF, including their osteogenesis, adipogenesis, and stromal supportive function and ability to support lymphocyte recruitment. Methods: Normal spinal peri-entheseal bone (PEB) and entheseal soft tissue (EST) were characterized for MSCs by immunophenotypic, osteogenic, chondrogenic, and adipogenic differentiation criteria. Functional and gene transcriptomic analysis was carried out on undifferentiated, adipo- differentiated, and osteo-differentiated MSCs. The enthesis C-C Motif Chemokine Ligand 20-C-C Motif Chemokine Receptor 6 (CCL20-CCR6) axis was investigated at transcript and protein levels to ascertain whether entheseal MSCs influence local immune cell populations. Results: Cultured MSCs from both PEB and EST displayed a tri-lineage differentiation ability. EST MSCs exhibited 4.9-fold greater adipogenesis (p < 0.001) and a 3-fold lower osteogenic capacity (p < 0.05). IL-17A induced greater osteogenesis in PEB MSCs compared to EST MSCs. IL-17A suppressed adipogenic differentiation, with a significant decrease in fatty acid-binding protein 4 (FABP4), peroxisome proliferator-activated receptor gamma (PPARγ), Cell Death Inducing DFFA Like Effector C (CIDEC), and Perilipin-1 (PLIN1). IL-17A significantly increased the CCL20 transcript (p < 0.01) and protein expression (p < 0.001) in MSCs supporting a role in type 17 lymphocyte recruitment. Conclusions: Normal spinal enthesis harbors resident MSCs with different in vitro functionalities in bone and soft tissue, especially in response to IL-17A, which enhanced osteogenesis and CCL20 production and reduced adipogenesis compared to unstimulated MSCs. This MSC-stromal-enthesis immune system may be a hitherto unappreciated mechanism of “fine tuning” tissue repair responses at the enthesis in health and could be relevant for SpA understanding.

mRNA expression of genes related to fat deposition during in vitro ovine adipogenesis

2019 ◽  
Vol 99 (4) ◽  
pp. 764-771 ◽  
Author(s):  
Baojun Li ◽  
Liying Qiao ◽  
Xiaoru Yan ◽  
Tao Shi ◽  
Duanyang Ren ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Binding Protein ◽  
Adipogenic Differentiation ◽  
Fat Deposition ◽  
Peroxisome Proliferator ◽  
Induced Differentiation ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
Ppar Γ

Fat deposition in animals involves adipogenic differentiation guided by transcriptional factors and other key factors. To understand the molecular mechanism underlying ovine adipogenic differentiation, the dynamic mRNA expression of key genes related to fat deposition, including peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid-binding protein 4 (FABP4), FABP5, and cellular retinoic acid-binding protein 2 (CRABP2), were analyzed during in vitro differentiation of ovine preadipocytes. The stromal vascular cells from underneath the tail fat tissue of 1-wk-old sheep were isolated and cultured, and the preadipocytes were induced using a cocktail of 3-isobutyl-1-methylxanthine, insulin, dexamethasone, and troglitazone. The cultivated cells were collected at different time points after induced differentiation. The expression levels of PPAR-γ, FABP4, FABP5, and CRABP2 were studied by quantitative real-time polymerase chain reaction. The expressions of these genes in sheep were compared with those in human and mouse retrieved from the Gene Expression Omnibus DataSets. We observed that the expression of PPAR-γ, FABP4, and FABP5 was increased upon differentiation of ovine preadipocytes, as in humans and mice. The expression of CRABP2 was sharply increased from days 0 to 2 after induced differentiation and was subsequently decreased. This expression pattern of CRABP2 was different from that observed in humans and mice. Our results provide new insights into the function of these genes in fat deposition.

scholarly journals Methacrylated gelatin/hyaluronan-based hydrogels for soft tissue engineering

2017 ◽  
Vol 8 ◽  
pp. 204173141774415 ◽  
Author(s):  
Lukas Kessler ◽  
Sandra Gehrke ◽  
Marc Winnefeld ◽  
Birgit Huber ◽  
Eva Hoch ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Soft Tissue ◽  
Adipogenic Differentiation ◽  
Building Blocks ◽  
Fatty Acid Binding ◽  
Angiogenic Potential ◽  
Adipose Tissue Engineering ◽  
Angiogenesis Assay ◽  
Soft Tissue Engineering

In vitro–generated soft tissue could provide alternate therapies for soft tissue defects. The aim of this study was to evaluate methacrylated gelatin/hyaluronan as scaffolds for soft tissue engineering and their interaction with human adipose–derived stem cells (hASCs). ASCs were incorporated into methacrylated gelatin/hyaluronan hydrogels. The gels were photocrosslinked with a lithium phenyl-2,4,6-trimethylbenzoylphosphinate photoinitiator and analyzed for cell viability and adipogenic differentiation of ASCs over a period of 30 days. Additionally, an angiogenesis assay was performed to assess their angiogenic potential. After 24 h, ASCs showed increased viability on composite hydrogels. These results were consistent over 21 days of culture. By induction of adipogenic differentiation, the mature adipocytes were observed after 7 days of culture, their number significantly increased until day 28 as well as expression of fatty acid binding protein 4 and adiponectin. Our scaffolds are promising as building blocks for adipose tissue engineering and allowed long viability, proliferation, and differentiation of ASCs.

scholarly journals Emilin-2 is a component of bone marrow extracellular matrix regulating mesenchymal stem cell differentiation and hematopoietic progenitors

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Francesco Da Ros ◽  
Luca Persano ◽  
Dario Bizzotto ◽  
Mariagrazia Michieli ◽  
Paola Braghetta ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Extracellular Matrix ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Adipogenic Differentiation ◽  
Stem Cell Differentiation ◽  
Dependent Manner ◽  
Hematopoietic Stem

Abstract Background Dissection of mechanisms involved in the regulation of bone marrow microenvironment through cell–cell and cell–matrix contacts is essential for the detailed understanding of processes underlying bone marrow activities both under physiological conditions and in hematologic malignancies. Here we describe Emilin-2 as an abundant extracellular matrix component of bone marrow stroma. Methods Immunodetection of Emilin-2 was performed in bone marrow sections of mice from 30 days to 6 months of age. Emilin-2 expression was monitored in vitro in primary and mesenchymal stem cell lines under undifferentiated and adipogenic conditions. Hematopoietic stem cells and progenitors in bone marrow of 3- to 10-month-old wild-type and Emilin-2 null mice were analyzed by flow cytometry. Results Emilin-2 is deposited in bone marrow extracellular matrix in an age-dependent manner, forming a meshwork that extends from compact bone boundaries to the central trabecular regions. Emilin-2 is expressed and secreted by both primary and immortalized bone marrow mesenchymal stem cells, exerting an inhibitory action in adipogenic differentiation. In vivo Emilin-2 deficiency impairs the frequency of hematopoietic stem/progenitor cells in bone marrow during aging. Conclusion Our data provide new insights in the contribution of bone marrow extracellular matrix microenvironment in the regulation of stem cell niches and hematopoietic progenitor differentiation.

scholarly journals Uptake and Distribution of Administered Bone Marrow Mesenchymal Stem Cell Extracellular Vesicles in Retina

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 730
Author(s):  
Biji Mathew ◽  
Leianne A. Torres ◽  
Lorea Gamboa Gamboa Acha ◽  
Sophie Tran ◽  
Alice Liu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Extracellular Vesicles ◽  
Time Course ◽  
Ganglion Cells ◽  
Ex Vivo ◽  
Dependent Manner ◽  
Paracrine Effects

Cell replacement therapy using mesenchymal (MSC) and other stem cells has been evaluated for diabetic retinopathy and glaucoma. This approach has significant limitations, including few cells integrated, aberrant growth, and surgical complications. Mesenchymal Stem Cell Exosomes/Extracellular Vesicles (MSC EVs), which include exosomes and microvesicles, are an emerging alternative, promoting immunomodulation, repair, and regeneration by mediating MSC’s paracrine effects. For the clinical translation of EV therapy, it is important to determine the cellular destination and time course of EV uptake in the retina following administration. Here, we tested the cellular fate of EVs using in vivo rat retinas, ex vivo retinal explant, and primary retinal cells. Intravitreally administered fluorescent EVs were rapidly cleared from the vitreous. Retinal ganglion cells (RGCs) had maximal EV fluorescence at 14 days post administration, and microglia at 7 days. Both in vivo and in the explant model, most EVs were no deeper than the inner nuclear layer. Retinal astrocytes, microglia, and mixed neurons in vitro endocytosed EVs in a dose-dependent manner. Thus, our results indicate that intravitreal EVs are suited for the treatment of retinal diseases affecting the inner retina. Modification of the EV surface should be considered for maintaining EVs in the vitreous for prolonged delivery.

Biomaterials Nano Geometry for Control of Stem Cell Differentiation

2009 ◽  
Vol 1239 ◽  
Author(s):  
Karla Brammer ◽  
Seunghan Oh ◽  
Sungho Jin
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Stem Cell Differentiation ◽  
Human Mesenchymal Stem Cell ◽  
Oxide Surface ◽  
Specific Cell ◽  
Implant Surface ◽  
Multipotent Stem Cells

AbstractTwo important goals in stem cell research are to control the cell proliferation without differentiation, and also to direct the differentiation into a specific cell lineage when desired. Recent studies indicate that the nanostructures substantially influence the stem cell behavior. It is well known that mesenchymal stem cells (MSCs) are multipotent stem cells that can differentiate into stromal lineages such as adipocyte, chondrocyte, fibroblast, myocyte, and osteoblast cell types. By examining the cellular behavior of MSCs cultured in vitro on nanostructures, some understanding of the effects that the nanostructures have on the stem cell’s response has been obtained. Here we demonstrate that TiO2 nanotubes produced by anodization on Ti implant surface can regulate human mesenchymal stem cell (hMSC) differentiation towards an osteoblast lineage in the absence of osteogenic inducing factors. Altering the dimensions of nanotubular-shaped titanium oxide surface structures independently allowed either augmented human mesenchymal stem cell (hMSC) adhesion at smaller diameter levels or a specific differentiation of hMSCs into osteoblasts using only the geometric cues. Small (˜30 nm diameter) nanotubes promoted adhesion without noticeable differentiation, while larger (˜70 - 100 nm diameter) nanotubes elicited a dramatic, ˜10 fold stem cell elongation, which induced cytoskeletal stress and selective differentiation into osteoblast-like cells, offering a promising nanotechnology-based route for novel orthopaedics-related hMSC treatments. The fact that a guided and preferential osteogenic differentiation of stem cells can be achieved using substrate nanotopography alone without using potentially toxic, differentiation-inducing chemical agents is significant, which can be useful for future development of novel and enhanced stem cell control and therapeutic implant development.

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