scholarly journals The nuclear import of the transcription factor MyoD is reduced in mesenchymal stem cells grown in a 3D micro-engineered niche

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Emanuela Jacchetti ◽  
Ramin Nasehi ◽  
Lucia Boeri ◽  
Valentina Parodi ◽  
Alessandro Negro ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Nuclear Envelope ◽  
Cell Fate ◽  
Nuclear Import ◽  
Numerical Models ◽  
Stem Cell Differentiation ◽  
Nuclear Pore

AbstractSmart biomaterials are increasingly being used to control stem cell fate in vitro by the recapitulation of the native niche microenvironment. By integrating experimental measurements with numerical models, we show that in mesenchymal stem cells grown inside a 3D synthetic niche both nuclear transport of a myogenic factor and the passive nuclear diffusion of a smaller inert protein are reduced. Our results also suggest that cell morphology modulates nuclear proteins import through a partition of the nuclear envelope surface, which is a thin but extremely permeable annular portion in cells cultured on 2D substrates. Therefore, our results support the hypothesis that in stem cell differentiation, the nuclear import of gene-regulating transcription factors is controlled by a strain-dependent nuclear envelope permeability, probably related to the reorganization of stretch-activated nuclear pore complexes.

scholarly journals Effect of the 3D Artificial Nichoid on the Morphology and Mechanobiological Response of Mesenchymal Stem Cells Cultured In Vitro

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1873 ◽  
Author(s):  
Andrea Remuzzi ◽  
Barbara Bonandrini ◽  
Matteo Tironi ◽  
Lorena Longaretti ◽  
Marina Figliuzzi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Cultured Cells ◽  
Three Dimensions ◽  
Nuclear Pore ◽  
Cells Cultured

Stem cell fate and behavior are affected by the bidirectional communication of cells and their local microenvironment (the stem cell niche), which includes biochemical cues, as well as physical and mechanical factors. Stem cells are normally cultured in conventional two-dimensional monolayer, with a mechanical environment very different from the physiological one. Here, we compare culture of rat mesenchymal stem cells on flat culture supports and in the “Nichoid”, an innovative three-dimensional substrate micro-engineered to recapitulate the architecture of the physiological niche in vitro. Two versions of the culture substrates Nichoid (single-layered or “2D Nichoid” and multi-layered or “3D Nichoid”) were fabricated via two-photon laser polymerization in a biocompatible hybrid organic-inorganic photoresist (SZ2080). Mesenchymal stem cells, isolated from rat bone marrow, were seeded on flat substrates and on 2D and 3D Nichoid substrates and maintained in culture up to 2 weeks. During cell culture, we evaluated cell morphology, proliferation, cell motility and the expression of a panel of 89 mesenchymal stem cells’ specific genes, as well as intracellular structures organization. Our results show that mesenchymal stem cells adhered and grew in the 3D Nichoid with a comparable proliferation rate as compared to flat substrates. After seeding on flat substrates, cells displayed large and spread nucleus and cytoplasm, while cells cultured in the 3D Nichoid were spatially organized in three dimensions, with smaller and spherical nuclei. Gene expression analysis revealed the upregulation of genes related to stemness and to mesenchymal stem cells’ features in Nichoid-cultured cells, as compared to flat substrates. The observed changes in cytoskeletal organization of cells cultured on 3D Nichoids were also responsible for a different localization of the mechanotransducer transcription factor YAP, with an increase of the cytoplasmic retention in cells cultured in the 3D Nichoid. This difference could be explained by alterations in the import of transcription factors inside the nucleus due to the observed decrease of mean nuclear pore diameter, by transmission electron microscopy. Our data show that 3D distribution of cell volume has a profound effect on mesenchymal stem cells structure and on their mechanobiological response, and highlight the potential use of the 3D Nichoid substrate to strengthen the potential effects of MSC in vitro and in vivo.

Predictive Modeling and Biomechanical Microengineering of Mesenchymal Stem Cells: A High Content Screening Platform to Enhance Lineage Specific Differentiation

2013 ◽  
Author(s):  
Amit Paul ◽  
David Franz ◽  
Sumaira Yahya ◽  
Shan Sun ◽  
Michael Cho
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Predictive Modeling ◽  
Stem Cell Differentiation ◽  
High Content Screening ◽  
Cell Behavior ◽  
Functional Changes ◽  
Screening Platform

Recent evidence suggests that stem cell differentiation can be regulated by modulation of the cell’s biomechanics. The cytoskeletal structures and arrangements in stem cells undergoing differentiation are dramatically altered, and these alterations vary by lineage. The complexity of events associated with the transformation of these precursor cells leaves many questions unanswered about morphological, structural, proteomic, and functional changes in differentiating stem cells. A thorough understanding of stem cell behavior, both experimentally and computationally, would allow for the development of more effective approaches to the expansion of stem cells in vitro and for the regulation of their commitment to a specific phenotype.

scholarly journals Functions of Circular RNAs in Regulating Adipogenesis of Mesenchymal Stem Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Fanglin Wang ◽  
Xiang Li ◽  
Zhiyuan Li ◽  
Shoushuai Wang ◽  
Jun Fan
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Stem Cell Differentiation ◽  
Circular Rna ◽  
Circular Rnas ◽  
Differentiation Process

The mesenchymal stem cells (MSCs) are known as highly plastic stem cells and can differentiate into specialized tissues such as adipose tissue, osseous tissue, muscle tissue, and nervous tissue. The differentiation of mesenchymal stem cells is very important in regenerative medicine. Their differentiation process is regulated by signaling pathways of epigenetic, transcriptional, and posttranscriptional levels. Circular RNA (circRNA), a class of noncoding RNAs generated from protein-coding genes, plays a pivotal regulatory role in many biological processes. Accumulated studies have demonstrated that several circRNAs participate in the cell differentiation process of mesenchymal stem cells in vitro and in vivo. In the current review, characteristics and functions of circRNAs in stem cell differentiation will be discussed. The mechanism and key role of circRNAs in regulating mesenchymal stem cell differentiation, especially adipogenesis, will be reviewed and discussed. Understanding the roles of these circRNAs will present us with a more comprehensive signal path network of modulating stem cell differentiation and help us discover potential biomarkers and therapeutic targets in clinic.

scholarly journals Osteogenic Response of Human Mesenchymal Stem Cells Analysed Using Combined Intracellular and Extracellular Metabolomic Monitoring

2021 ◽  
Vol 55 (3) ◽  
pp. 311-326
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Osteogenic Differentiation ◽  
Bone Microarchitecture ◽  
Human Mesenchymal Stem Cells ◽  
Stem Cell Differentiation ◽  
Extracellular Metabolite ◽  
Osteogenic Response

Background/Aims: The skeleton is a metabolically active organ undergoing continuous remodelling initiated by mesenchymal progenitors present in bone and bone marrow. Under certain pathological conditions this remodelling balance shifts towards increased resorption resulting in weaker bone microarchitecture, and there is consequently a therapeutic need to identify pathways that could inversely enhance bone formation from stem cells. Metabolomics approaches recently applied to stem cell characterisation could help identify new biochemical markers involved in osteogenic differentiation. Methods: Combined intra- and extracellular metabolite profiling was performed by liquid chromatography-mass spectrometry (LC-MS) on human mesenchymal stem cells (MSCs) undergoing osteogenic differentiation in vitro. Using a combination of univariate and multivariate analyses, changes in metabolite and nutrient concentration were monitored in cultures under osteogenic treatment over 10 days. Results: A subset of differentially detected compounds was identified in differentiating cells, suggesting a direct link to metabolic processes involved in osteogenic response. Conclusion: These results highlight new metabolite candidates as potential biomarkers to monitor stem cell differentiation towards the bone lineage.

scholarly journals Advances in Extracellular Matrix-Mimetic Hydrogels to Guide Stem Cell Fate

2021 ◽  
pp. 1-18
Author(s):  
Ryan S. Stowers
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Stem Cell ◽  
Cell Fate ◽  
Cell Biology ◽  
Stem Cell Differentiation ◽  
Stem Cell Biology ◽  
Stem Cell Fate ◽  
Material Systems

In the fields of regenerative medicine and tissue engineering, stem cells offer vast potential for treating or replacing diseased and damaged tissue. Much progress has been made in understanding stem cell biology, yielding protocols for directing stem cell differentiation toward the cell type of interest for a specific application. One particularly interesting and powerful signaling cue is the extracellular matrix (ECM) surrounding stem cells, a network of biopolymers that, along with cells, makes up what we define as a tissue. The composition, structure, biochemical features, and mechanical properties of the ECM are varied in different tissues and developmental stages, and serve to instruct stem cells toward a specific lineage. By understanding and recapitulating some of these ECM signaling cues through engineered ECM-mimicking hydrogels, stem cell fate can be directed in vitro. In this review, we will summarize recent advances in material systems to guide stem cell fate, highlighting innovative methods to capture ECM functionalities and how these material systems can be used to provide basic insight into stem cell biology or make progress toward therapeutic objectives.

scholarly journals Hijacking the Cellular Mail: Exosome Mediated Differentiation of Mesenchymal Stem Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Raghuvaran Narayanan ◽  
Chun-Chieh Huang ◽  
Sriram Ravindran
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Regenerative Medicine ◽  
Cell Fate ◽  
Type I Collagen ◽  
Stem Cell Differentiation ◽  
Future Research ◽  
Type I ◽  
Specific Differentiation

Bone transplantation is one of the most widely performed clinical procedures. Consequently, bone regeneration using mesenchymal stem cells and tissue engineering strategies is one of the most widely researched fields in regenerative medicine. Recent scientific consensus indicates that a biomimetic approach is required to achieve proper regeneration of any tissue. Exosomes are nanovesicles secreted by cells that act as messengers that influence cell fate. Although exosomal function has been studied with respect to cancer and immunology, the role of exosomes as inducers of stem cell differentiation has not been explored. We hypothesized that exosomes can be used as biomimetic tools for regenerative medicine. In this study we have explored the use of cell-generated exosomes as tools to induce lineage specific differentiation of stem cells. Our results indicate that proosteogenic exosomes isolated from cell cultures can induce lineage specific differentiation of naïve MSCsin vitroandin vivo. Additionally, exosomes can also bind to matrix proteins such as type I collagen and fibronectin enabling them to be tethered to biomaterials. Overall, the results from this study show the potential of cell derived exosomes in bone regenerative medicine and opens up new avenues for future research.

scholarly journals Nuclear Export of Smads by RanBP3L Regulates Bone Morphogenetic Protein Signaling and Mesenchymal Stem Cell Differentiation

2015 ◽  
Vol 35 (10) ◽  
pp. 1700-1711 ◽  
Author(s):  
Fenfang Chen ◽  
Xia Lin ◽  
Pinglong Xu ◽  
Zhengmao Zhang ◽  
Yanzhen Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Mesenchymal Stem Cell ◽  
Nuclear Export ◽  
Stem Cell Differentiation ◽  
Bmp Signaling ◽  
Dependent Manner ◽  
Mesenchymal Stem Cell Differentiation

Bone morphogenetic proteins (BMPs) play vital roles in regulating stem cell maintenance and differentiation. BMPs can induce osteogenesis and inhibit myogenesis of mesenchymal stem cells. Canonical BMP signaling is stringently controlled through reversible phosphorylation and nucleocytoplasmic shuttling of Smad1, Smad5, and Smad8 (Smad1/5/8). However, how the nuclear export of Smad1/5/8 is regulated remains unclear. Here we report that the Ran-binding protein RanBP3L acts as a nuclear export factor for Smad1/5/8. RanBP3L directly recognizes dephosphorylated Smad1/5/8 and mediates their nuclear export in a Ran-dependent manner. Increased expression of RanBP3L blocks BMP-induced osteogenesis of mouse bone marrow-derived mesenchymal stem cells and promotes myogenic induction of C2C12 mouse myoblasts, whereas depletion of RanBP3L expression enhances BMP-dependent stem cell differentiation activity and transcriptional responses. In conclusion, our results demonstrate that RanBP3L, as a nuclear exporter for BMP-specific Smads, plays a critical role in terminating BMP signaling and regulating mesenchymal stem cell differentiation.

Magnetic field assisted stem cell differentiation – role of substrate magnetization in osteogenesis

2015 ◽  
Vol 3 (16) ◽  
pp. 3150-3168 ◽  
Author(s):  
Sunil Kumar Boda ◽  
Greeshma Thrivikraman ◽  
Bikramjit Basu
Keyword(s):  
Magnetic Field ◽  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Bone Tissue Engineering ◽  
Human Mesenchymal Stem Cells ◽  
Stem Cell Differentiation

Substrate magnetization as a tool for modulating the osteogenesis of human mesenchymal stem cells for bone tissue engineering applications.

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.

scholarly journals Comparison of the Proliferation and Differentiation Potential of Human Urine-, Placenta Decidua Basalis-, and Bone Marrow-Derived Stem Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Chengguang Wu ◽  
Long Chen ◽  
Yi-zhou Huang ◽  
Yongcan Huang ◽  
Ornella Parolini ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Stem Cell Differentiation ◽  
Cell Types ◽  
Stem Cell Marker ◽  
Differentiation Potential ◽  
Multipotent Stem Cells ◽  
Decidua Basalis

Human multipotent stem cell-based therapies have shown remarkable potential in regenerative medicine and tissue engineering applications due to their abilities of self-renewal and differentiation into multiple adult cell types under appropriate conditions. Presently, human multipotent stem cells can be isolated from different sources, but variation among their basic biology can result in suboptimal selection of seed cells in preclinical and clinical research. Thus, the goal of this study was to compare the biological characteristics of multipotent stem cells isolated from human bone marrow, placental decidua basalis, and urine, respectively. First, we found that urine-derived stem cells (USCs) displayed different morphologies compared with other stem cell types. USCs and placenta decidua basalis-derived mesenchymal stem cells (PDB-MSCs) had superior proliferation ability in contrast to bone marrow-derived mesenchymal stem cells (BMSCs); these cells grew to have the highest colony-forming unit (CFU) counts. In phenotypic analysis using flow cytometry, similarity among all stem cell marker expression was found, excluding CD29 and CD105. Regarding stem cell differentiation capability, USCs were observed to have better adipogenic and endothelial abilities as well as vascularization potential compared to BMSCs and PDB-MSCs. As for osteogenic and chondrogenic induction, BMSCs were superior to all three stem cell types. Future therapeutic indications and clinical applications of BMSCs, PDB-MSCs, and USCs should be based on their characteristics, such as growth kinetics and differentiation capabilities.

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