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.

Murine Osteochondral Stem Cells Express Collagen Type I More Strongly on PDMS Substrates Than on Tissue Culture Plastic

2013 ◽  
Author(s):  
William S. Van Dyke ◽  
Ozan Akkus ◽  
Eric Nauman
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Cells ◽  
Stem Cell Differentiation ◽  
Collagen Type I ◽  
Fiber Formation ◽  
Substrate Stiffness ◽  
Type I ◽  
Differentiation Potential

The discovery of the multipotent lineage of mesenchymal stem cells has dawned a new age in tissue engineering, where an autologous cell-seeded scaffold can be implanted into different therapeutic sites. Mesenchymal stem cells have been reported to differentiate into numerous anchorage-dependent cell phenotypes, including neurons, adipocytes, myoblasts, chondrocytes, tenocytes, and osteoblasts. A seminal work detailing that mesenchymal stem cells can be directed towards differentiation of different cell types by substrate stiffness alone [1] has led to numerous studies attempting to understand how cells can sense the stiffness of their substrate [2–3] Substrate stiffness has been shown to be an inducer of stem cell differentiation. MSCs on extremely soft substrates (250 Pa), similar to the stiffness of bone marrow, became quiescent but still retained their multipotency [4]. Elastic substrates in the stiffness range of 34 kPa revealed MSCs with osteoblast morphology, and osteocalcin along with other osteoblast markers were expressed [1]. However, osteogenesis has been found to increase on much stiffer (20–80 kPa) [5–6] (400 kPa) [7] as well as much softer substrates (75 Pa) [8]. Overall, cells have increased projected cell area and proliferation on stiffer substrates, leading to higher stress fiber formation. This study seeks to understand if the stiffness of the substrate has any effect on the differentiation potential of osteochondral progenitor cells into bone cells, using an in vitro dual fluorescent mouse model.

scholarly journals 3D Biomimetic Scaffold for Growth Factor Controlled Delivery: An In-Vitro Study of Tenogenic Events on Wharton’s Jelly Mesenchymal Stem Cells

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1448
Author(s):  
Maria Camilla Ciardulli ◽  
Joseph Lovecchio ◽  
Pasqualina Scala ◽  
Erwin Pavel Lamparelli ◽  
Tina Patricia Dale ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Type I Collagen ◽  
In Vitro Study ◽  
Wharton’S Jelly ◽  
Controlled Delivery ◽  
Type I ◽  
Wharton's Jelly

The present work described a bio-functionalized 3D fibrous construct, as an interactive teno-inductive graft model to study tenogenic potential events of human mesenchymal stem cells collected from Wharton’s Jelly (hWJ-MSCs). The 3D-biomimetic and bioresorbable scaffold was functionalized with nanocarriers for the local controlled delivery of a teno-inductive factor, i.e., the human Growth Differentiation factor 5 (hGDF-5). Significant results in terms of gene expression were obtained. Namely, the up-regulation of Scleraxis (350-fold, p ≤ 0.05), type I Collagen (8-fold), Decorin (2.5-fold), and Tenascin-C (1.3-fold) was detected at day 14; on the other hand, when hGDF-5 was supplemented in the external medium only (in absence of nanocarriers), a limited effect on gene expression was evident. Teno-inductive environment also induced pro-inflammatory, (IL-6 (1.6-fold), TNF (45-fold, p ≤ 0.001), and IL-12A (1.4-fold)), and anti-inflammatory (IL-10 (120-fold) and TGF-β1 (1.8-fold)) cytokine expression upregulation at day 14. The presented 3D construct opens perspectives for the study of drug controlled delivery devices to promote teno-regenerative events.

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 Effects of bone marrow mesenchymal stem cell-derived exosomes on bone formation on titanium

2020 ◽  
Author(s):  
Xiaoling Zhang ◽  
Liangzhi Du ◽  
Ningbo Zhao ◽  
Lizhe Zhu ◽  
Lei Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Type I Collagen ◽  
Control Group ◽  
Type I ◽  
Oral Implants ◽  
Marrow Mesenchymal Stem Cells

Abstract Background: In recent years, researchers have found that exosomes, an important component of intercellular signal transduction and exchange, have great significance in bone tissue repair. In this study, to further promote the development of oral implants, preliminary in vitro experiments were conducted to verify the different concentrations of exosomes from bone marrow mesenchymal stem cells (BMSC-exos) for osteogenesis on the surfaces of titanium sheets.Methods: In this experiment, rabbit bone marrow mesenchymal stem cells(BMSCs) were seeded on the surfaces of 10 mm × 10 mm × 1 mm square titanium sheets and were divided into four groups to investigate their adsorption, proliferation and osteogenesis after treatment with different concentrations of BMSC-exos: 1. BMSCs + titanium + 0 µg/ml BMSC-exos; 2. BMSCs + titanium + 10 µg/ml BMSC-exos; 3. BMSCs + titanium + 25 µg/ml BMSC-exos; and 4. BMSCs + titanium + 50 µg/ml BMSC-exos.Results: Compared with the control group, BMSCs’ adsorption, extension, proliferation and osteogenesis on titanium sheets were significantly increased in the Exosomes group.Conclusions: Exosomes can promote the bone formation of BMSCs on titanium plates by promoting adsorption, extension, proliferation, production of alkaline phosphatase(ALP) and type I collagen and mineralization during the osteogenesis process.

APPLICATION OF DENDRIMER/PLASMID hBMP-2 COMPLEXES LOADED INTO β-TCP/COLLAGEN SCAFFOLD IN THE TREATMENT OF FEMORAL DEFECTS IN RATS

2014 ◽  
Vol 26 (01) ◽  
pp. 1450005 ◽  
Author(s):  
Tingwei Bao ◽  
Huiming Wang ◽  
Wentao Zhang ◽  
Xuefeng Xia ◽  
Jiabei Zhou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Type I Collagen ◽  
Cell Attachment ◽  
Collagen Scaffold ◽  
Bone Defects ◽  
Bone Morphogenetic Protein 2 ◽  
Porous Scaffolds ◽  
Type I

Purpose: Plasmid loading into scaffolds to enhance sustained release of growth factors is an important focus of regenerative medicine. The aim of this study was to build gene-activated matrices (GAMs) and examine the bone augmentation properties. Methods: Generation 5 polyamidoamine dendrimers (G5 dPAMAM)/plasmid recombinant human bone morphogenetic protein-2 (rhBMP-2) complexes were immobilized into beta-tricalcium phosphate (β-TCP)/type I collagen porous scaffolds. After cultured with rat mesenchymal stem cells (rMSCs), transfection efficiencies were examined. The secretion of rhBMP-2 and alkaline phosphatase (ALP) were detected to evaluate the osteogenic properties. Scanning electron microscopy (SEM) was used to observe attachment and proliferation. Moreover, we applied these GAMs directly into freshly created segmental bone defects in rat femurs, and their osteogenic efficiencies were evaluated. Results: Released plasmid complexes were transfected into stem cells and were expressed, which caused osteogenic differentiations of rat mesenchymal stem cells (rMSCs). SEM analysis showed excellent cell attachment. Bioactivity of plasmid rhBMP-2 was maintained in vivo, and the X-ray observation, histological analysis and immunohistochemistry (IHC) of bone tissue demonstrated that the bone healing in segmental femoral defects was enhanced by implantation of GAMs. Conclusions: Such biomaterials offer therapeutic opportunities in critical-sized bone defects.

scholarly journals Cell-Free Demineralized Bone Matrix for Mesenchymal Stem Cells Survival and Colonization

Materials ◽  
2019 ◽  
Vol 12 (9) ◽  
pp. 1360 ◽  
Author(s):  
Monica Mattioli-Belmonte ◽  
Francesca Montemurro ◽  
Caterina Licini ◽  
Iolanda Iezzi ◽  
Manuela Dicarlo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tissue Regeneration ◽  
Demineralized Bone Matrix ◽  
Bone Matrix ◽  
Morphological Observation ◽  
Type I ◽  
Demineralized Bone

Decellularized bone matrix is receiving much attention as biological scaffolds and implantable biomaterials for bone tissue regeneration. Here, we evaluated the efficacy of a cell-free demineralized bone matrix on mesenchymal stem cells (MSCs) survival and differentiation in vitro. The seeding of human umbilical cord-derived MSCs (hUC-SCs) on decellularized bone matrices up to 14 days was exploited, assessing their capability of scaffold colonization and evaluating gene expression of bone markers. Light and Scanning Electron Microscopies were used. The obtained cell-free decalcified structures showed elastic moduli attributable to both topology and biochemical composition. Morphological observation evidenced an almost complete colonization of the scaffolds after 14 days of culture. Moreover, in hUC-SCs cultured on decalcified scaffolds, without the addition of any osteoinductive media, there was an upregulation of Collagen Type I (COL1) and osteonectin (ON) gene expression, especially on day 14. Modifications in the expression of genes engaged in stemness were also detected. In conclusion, the proposed decellularized bone matrix can induce the in vitro hUC-SCs differentiation and has the potential to be tested for in in vivo tissue regeneration.

scholarly journals Cycloastragenol as an Exogenous Enhancer of Chondrogenic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells. A Morphological Study

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 347 ◽  
Author(s):  
Marta Anna Szychlinska ◽  
Giovanna Calabrese ◽  
Silvia Ravalli ◽  
Nunziatina Laura Parrinello ◽  
Stefano Forte ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Chondrogenic Differentiation ◽  
Hydrolysis Product ◽  
Cartilage Regeneration ◽  
Triterpenoid Saponin ◽  
Type I ◽  
Chondrocyte Phenotype

Stem cell therapy and tissue engineering represent a promising approach for cartilage regeneration. However, they present limits in terms of mechanical properties and premature de-differentiation of engineered cartilage. Cycloastragenol (CAG), a triterpenoid saponin compound and a hydrolysis product of the main ingredient in Astragalus membranaceous, has been explored for cartilage regeneration. The aim of this study was to investigate CAG’s ability to promote cell proliferation, maintain cells in their stable active phenotype, and support the production of cartilaginous extracellular matrix (ECM) in human adipose-derived mesenchymal stem cells (hAMSCs) in up to 28 days of three-dimensional (3D) chondrogenic culture. The hAMSC pellets were cultured in chondrogenic medium (CM) and in CM supplemented with CAG (CAG–CM) for 7, 14, 21, and 28 days. At each time-point, the pellets were harvested for histological (hematoxylin and eosin (H&E)), histochemical (Alcian-Blue) and immunohistochemical analysis (Type I, II, and X collagen, aggrecan, SOX9, lubricin). After excluding CAG’s cytotoxicity (MTT Assay), improved cell condensation, higher glycosaminoglycans (sGAG) content, and increased cell proliferation have been detected in CAG–CM pellets until 28 days of culture. Overall, CAG improved the chondrogenic differentiation of hAMSCs, maintaining stable the active chondrocyte phenotype in up to 28 days of 3D in vitro chondrogenic culture. It is proposed that CAG might have a beneficial impact on cartilage regeneration approaches.

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.

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