Functions of Circular RNAs in Regulating Adipogenesis of Mesenchymal Stem Cells

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.

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Decellularized Extracellular Matrix as anIn VitroModel to Study the Comprehensive Roles of the ECM in Stem Cell Differentiation

Stem Cells International ◽

10.1155/2016/6397820 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 73

Author(s):

Takashi Hoshiba ◽

Guoping Chen ◽

Chiho Endo ◽

Hiroka Maruyama ◽

Miyuki Wakui ◽

...

Keyword(s):

Stem Cells ◽

Extracellular Matrix ◽

Stem Cell ◽

Cell Differentiation ◽

Regenerative Medicine ◽

Intracellular Signaling ◽

Complex Structure ◽

Stem Cell Differentiation

Stem cells are a promising cell source for regenerative medicine. Stem cell differentiation must be regulated for applications in regenerative medicine. Stem cells are surrounded by extracellular matrix (ECM)in vivo. The ECM is composed of many types of proteins and glycosaminoglycans that assemble into a complex structure. The assembly of ECM molecules influences stem cell differentiation through orchestrated intracellular signaling activated by many ECM molecules. Therefore, it is important to understand the comprehensive role of the ECM in stem cell differentiation as well as the functions of the individual ECM molecules. Decellularized ECM is a usefulin vitromodel for studying the comprehensive roles of ECM because it retains a native-like structure and composition. Decellularized ECM can be obtained fromin vivotissue ECM or ECM fabricated by cells culturedin vitro. It is important to select the correct decellularized ECM because each type has different properties. In this review, tissue-derived and cell-derived decellularized ECMs are compared asin vitroECM models to examine the comprehensive roles of the ECM in stem cell differentiation. We also summarize recent studies using decellularized ECM to determine the comprehensive roles of the ECM in stem cell differentiation.

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

Molecular and Cellular Biology ◽

10.1128/mcb.00121-15 ◽

2015 ◽

Vol 35 (10) ◽

pp. 1700-1711 ◽

Cited By ~ 15

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.

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

Journal of Materials Chemistry B ◽

10.1039/c5tb00118h ◽

2015 ◽

Vol 3 (16) ◽

pp. 3150-3168 ◽

Cited By ~ 29

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.

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Xenogenic Implantation of Equine Synovial Fluid-Derived Mesenchymal Stem Cells Leads to Articular Cartilage Regeneration

Stem Cells International ◽

10.1155/2018/1073705 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 10

Author(s):

Mohammed Zayed ◽

Steven Newby ◽

Nabil Misk ◽

Robert Donnell ◽

Madhu Dhar

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Articular Cartilage ◽

Synovial Fluid ◽

Cartilage Repair ◽

Cartilage Regeneration ◽

Large Animal

Horses are widely used as large animal preclinical models for cartilage repair studies, and hence, there is an interest in using equine synovial fluid-derived mesenchymal stem cells (SFMSCs) in research and clinical applications. Since, we have previously reported that similar to bone marrow-derived MSCs (BMMSCs), SFMSCs may also exhibit donor-to-donor variations in their stem cell properties; the current study was carried out as a proof-of-concept study, to compare the in vivo potential of equine BMMSCs and SFMSCs in articular cartilage repair. MSCs from these two sources were isolated from the same equine donor. In vitro analyses confirmed a significant increase in COMP expression in SFMSCs at day 14. The cells were then encapsulated in neutral agarose scaffold constructs and were implanted into two mm diameter full-thickness articular cartilage defect in trochlear grooves of the rat femur. MSCs were fluorescently labeled, and one week after treatment, the knee joints were evaluated for the presence of MSCs to the injured site and at 12 weeks were evaluated macroscopically, histologically, and then by immunofluorescence for healing of the defect. The macroscopic and histological evaluations showed better healing of the articular cartilage in the MSCs’ treated knee than in the control. Interestingly, SFMSC-treated knees showed a significantly higher Col II expression, suggesting the presence of hyaline cartilage in the healed defect. Data suggests that equine SFMSCs may be a viable option for treating osteochondral defects; however, their stem cell properties require prior testing before application.

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A Biofunctional Fibrous Scaffold for the Encapsulation of Human Mesenchymal Stem Cells and its Effects on Stem Cell Differentiation

IFMBE Proceedings - 13th International Conference on Biomedical Engineering ◽

10.1007/978-3-540-92841-6_314 ◽

2009 ◽

pp. 1279-1281

Author(s):

S. Z. Yow ◽

C. H. Quek ◽

E. K. F. Yim ◽

K. W. Leong ◽

C. T. Lim

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Cell Differentiation ◽

Human Mesenchymal Stem Cells ◽

Stem Cell Differentiation ◽

Fibrous Scaffold

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Human adipose stem cell differentiation is highly affected by cancer cells both in vitro and in vivo: implication for autologous fat grafting

Cell Death and Disease ◽

10.1038/cddis.2016.308 ◽

2017 ◽

Vol 8 (1) ◽

pp. e2568-e2568 ◽

Cited By ~ 31

Author(s):

Francesca Paino ◽

Marcella La Noce ◽

Diego Di Nucci ◽

Giovanni Francesco Nicoletti ◽

Rosa Salzillo ◽

...

Keyword(s):

Stem Cell ◽

Cell Differentiation ◽

Stem Cell Differentiation ◽

Fat Grafting ◽

Adipose Stem Cell ◽

Autologous Fat Grafting ◽

Autologous Fat ◽

Human Adipose Stem Cell

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

Volume 1B: Extremity; Fluid Mechanics; Gait; Growth, Remodeling, and Repair; Heart Valves; Injury Biomechanics; Mechanotransduction and Sub-Cellular Biophysics; MultiScale Biotransport; Muscle, Tendon and Ligament; Musculoskeletal Devices; Multiscale Mechanics; Thermal Medicine; Ocular Biomechanics; Pediatric Hemodynamics; Pericellular Phenomena; Tissue Mechanics; Biotransport Design and Devices; Spine; Stent Device Hemodynamics; Vascular Solid Mechanics; Student Paper and Design Competitions ◽

10.1115/sbc2013-14639 ◽

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.

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

Cells ◽

10.3390/cells9081873 ◽

2020 ◽

Vol 9 (8) ◽

pp. 1873 ◽

Cited By ~ 3

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.

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Identification of mesenchymal stem cell differentiation state using dual-micropore microfluidic impedance flow cytometry

Analytical Methods ◽

10.1039/c6ay01377e ◽

2016 ◽

Vol 8 (41) ◽

pp. 7437-7444 ◽

Cited By ~ 13

Author(s):

Hongjun Song ◽

Jenna M. Rosano ◽

Yi Wang ◽

Charles J. Garson ◽

Balabhaskar Prabhakarpandian ◽

...

Keyword(s):

Stem Cells ◽

Flow Cytometry ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Cell Differentiation ◽

Mesenchymal Stem Cell ◽

Electrical Impedance ◽

Stem Cell Differentiation ◽

Non Invasive ◽

Mesenchymal Stem Cell Differentiation

A dual-micropore-based microfluidic electrical impedance flow cytometer for non-invasive identification of the differentiation state of mesenchymal stem cells.

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