scholarly journals Isolation, Characterization, and Agent-Based Modeling of Mesenchymal Stem Cells in a Bio-construct for Myocardial Regeneration Scaffold Design

Data ◽  
2019 ◽  
Vol 4 (2) ◽  
pp. 71 ◽  
Author(s):  
Diana Victoria Ramírez López ◽  
María Isabel Melo Escobar ◽  
Carlos A. Peña-Reyes ◽  
Álvaro J. Rojas Arciniegas ◽  
Paola Andrea Neuta Arciniegas
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
In Silico ◽  
Cardiac Tissue ◽  
Cellular Level ◽  
Cell Behavior ◽  
Agent Based Model ◽  
Agent Based ◽  
And Migration

Regenerative medicine involves methods to control and modify normal tissue repair processes. Polymer and cell constructs are under research to create tissue that replaces the affected area in cardiac tissue after myocardial infarction (MI). The aim of the present study is to evaluate the behavior of differentiated and undifferentiated mesenchymal stem cells (MSCs) in vitro and in silico and to compare the results that both offer when it comes to the design process of biodevices for the treatment of infarcted myocardium in biomodels. To assess in vitro behavior, MSCs are isolated from rat bone marrow and seeded undifferentiated and differentiated in multiple scaffolds of a gelled biomaterial. Subsequently, cell behavior is evaluated by trypan blue and fluorescence microscopy, which showed that the cells presented high viability and low cell migration in the biomaterial. An agent-based model intended to reproduce as closely as possible the behavior of individual MSCs by simulating cellular-level processes was developed, where the in vitro results are used to identify parameters in the agent-based model that is developed, and which simulates cellular-level processes: Apoptosis, differentiation, proliferation, and migration. Thanks to the results obtained, suggestions for good results in the design and fabrication of the proposed scaffolds and how an agent-based model can be helpful for testing hypothesis are presented in the discussion. It is concluded that assessment of cell behavior through the observation of viability, proliferation, migration, inflammation reduction, and spatial composition in vitro and in silico, represents an appropriate strategy for scaffold engineering.

scholarly journals Influence of Egr-1 in Cardiac Tissue-Derived Mesenchymal Stem Cells in Response to Glucose Variations

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Daniela Bastianelli ◽  
Camilla Siciliano ◽  
Rosa Puca ◽  
Andrea Coccia ◽  
Colin Murdoch ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Target Genes ◽  
Cardiac Tissue ◽  
Early Response ◽  
Induced Response ◽  
Protein Levels ◽  
Short Period ◽  
Phenotype Analysis

Mesenchymal stem cells (MSCs) represent a promising cell population for cell therapy and regenerative medicine applications. However, how variations in glucose are perceived by MSC pool is still unclear. Since, glucose metabolism is cell type and tissue dependent, this must be considered when MSCs are derived from alternative sources such as the heart. The zinc finger transcription factor Egr-1 is an important early response gene, likely to play a key role in the glucose-induced response. Our aim was to investigate how short-term changes inin vitroglucose concentrations affect multipotent cardiac tissue-derived MSCs (cMSCs) in a mouse model of Egr-1 KO (Egr-1−/−). Results showed that loss of Egr-1 does not significantly influence cMSC proliferation. In contrast, responses to glucose variations were observed in wt but not in Egr-1−/−cMSCs by clonogenic assay. Phenotype analysis by RT-PCR showed that cMSCs Egr-1−/−lost the ability to regulate the glucose transporters GLUT-1 and GLUT-4 and, as expected, the Egr-1 target genes VEGF, TGFβ-1, and p300. Acetylated protein levels of H3 histone were impaired in Egr-1−/−compared to wt cMSCs. We propose that Egr-1 acts as immediate glucose biological sensor in cMSCs after a short period of stimuli, likely inducing epigenetic modifications.

Overexpression of FOXQ1 enhances anti-senescence and migration effects of human umbilical cord mesenchymal stem cells in vitro and in vivo

2018 ◽  
Vol 373 (2) ◽  
pp. 379-393 ◽  
Author(s):  
Tao Zhang ◽  
Pan Wang ◽  
Yanxia Liu ◽  
Jiankang Zhou ◽  
Zhenqing Shi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Human Umbilical Cord ◽  
And Migration

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 The impact of cryopreservation on bone marrow-derived mesenchymal stem cells: a systematic review

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Soukaina Bahsoun ◽  
Karen Coopman ◽  
Elizabeth C. Akam
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cell Types ◽  
Surface Marker Expression ◽  
Wide Range ◽  
And Migration ◽  
The Impact

AbstractMesenchymal stem cells (MSCs) represent an invaluable asset for the field of cell therapy. Human Bone marrow-derived MSCs (hBM-MSCs) are one of the most commonly used cell types in clinical trials. They are currently being studied and tested for the treatment of a wide range of diseases and conditions. The future availability of MSCs therapies to the public will require a robust and reliable delivery process. Cryopreservation represents the gold standard in cell storage and transportation, but its effect on BM-MSCs is still not well established. A systematic review was conducted to evaluate the impact of cryopreservation on BM-MSCs and to attempt to uncover the reasons behind some of the controversial results reported in the literature. Forty-one in vitro studies were analysed, and their results organised according to the cell attributes they assess. It was concluded that cryopreservation does not affect BM-MSCs morphology, surface marker expression, differentiation or proliferation potential. However, mixed results exist regarding the effect on colony forming ability and the effects on viability, attachment and migration, genomic stability and paracrine function are undefined mainly due to the huge variabilities governing the cryopreservation process as a whole and to the lack of standardised assays.

The Hematopoietic Supportive Function of Adult Bone Marrow Mesenchymal Stem Cells Is Lost after Differentiation Induction towards Adipocytic, Osteoblastic and Vascular Smooth Muscle Lineages

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4742-4742
Author(s):  
Tatiana Ribeiro ◽  
Aurelie Picard ◽  
Elfi Ducrocq ◽  
Alain Langonne ◽  
Philippe Rosset ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Stromal Cells ◽  
Expansion Medium ◽  
Hsc Niche ◽  
And Migration

Abstract The bone marrow (BM) hematopoietic stem cell (HSC) niche is a specialized structure of the microenvironment, which supports survival and regulates HSC function (i.e. the HSC control of the self-renewal/differentiation balance and migration). The supportive cells involved in the HSC niche are usually named as “stromal cells” but their precise nature remains a matter of debate (in particular, to know whether these cells belong to osteoblastic or to vascular smooth muscle lineage). Mesenchymal stem cells (MSCs) that are present into the BM are characterized by a broad differentiation potential including adipocytic (A), osteoblastic (O) and vascular smooth muscle (V) pathways. Although MSCs are believed to be at the origin of stromal cells, their real function within the niche is unknown. The aim of this study was to investigate in vitro the hematopoietic function (HSC support and migration) of cultured adult BM MSCs non-differentiated and during induced differentiation along A, O and V lineages. MSCs were obtained from BM nucleated cells of patients undergoing orthopedic surgery by culture in expansion medium (alpha-MEM medium with 10% FCS and 1 ng/mL FGF-2). The MSCs were tested before (cultured in expansion medium) and during differentiation induction in appropriate medium for A, O or V lineages (from 3 to 21 days). Interestingly, non-differentiated MSCs already co-expressed O (PTH-receptor), A (leptin) and V (ASMA) markers as assessed by Western blotting. Capacity of MSCs to support hematopoiesis was evaluated by long-term cultures (for 5 wks) with BM CD34+ cells in limiting dilution (CAFC assay), and capacity to control CD34+ cell migration by using Transwells seeded with MSCs (trans-stromal migration assay). We showed that non-differentiated MSCs have the most important capacity to support hematopoiesis (5-week CAFC frequency) and that this capacity was quickly and dramatically lost from 3 days of differentiation towards A (36±2% of non-differentiated values), O (40±3%) and V (38±1%) lineages. This capacity was almost abolished after 14 days of A, O and V differentiation (<5%). In parallel, CD34+ cell migration was clearly reduced through 3-day A and O differentiated MSCs, while it was increased through 3-day V differentiated MSCs (5 fold). These results show that MSCs maintained in vitro in non-differentiated state (although already expressing some A, O and V markers), display the strongest hematopoietic supportive activity compared to MSCs induced to differentiate into adipocytic, osteoblastic, or vascular smooth muscle lineages. Therefore, the stromal cell function could be supported by a cell close to a non-differentiated MSC in endosteal or perivascular niches as well. In contrast, vascular smooth muscle differentiated MSCs at advanced stages could be devoted rather to HSC migration control than to HSC support.

scholarly journals Transplantation of Hypoxic-Preconditioned Bone Mesenchymal Stem Cells Retards Intervertebral Disc Degeneration via Enhancing Implanted Cell Survival and Migration in Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Weiheng Wang ◽  
Yang Wang ◽  
Guoying Deng ◽  
Jun Ma ◽  
Xiaodong Huang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Protein Expression ◽  
Matrix Protein ◽  
Caspase 3 ◽  
Bone Mesenchymal Stem Cells ◽  
Collagen Ii ◽  
And Migration ◽  
Ivd Degeneration

Objective. Special hypoxic and hypertonic microenvironment in intervertebral discs (IVDs) decreases the treatment effect of cell transplantation. We investigated the hypothesis that hypoxic preconditioning (HP) could improve the therapeutic effect of bone mesenchymal stem cells (BMSCs) to IVD degeneration. Methods. BMSCs from green fluorescent protein-transgenic rats were pretreated with cobalt chloride (CoCl2, 100 μM, 24 h) for hypoxic conditions in vitro. Apoptosis (related pathways of caspase-3 and bcl-2) and migration (related pathways of HIF-1α and CXCR4) were detected in BMSCs. In vivo, BMSCs and HP BMSCs (H-BMSCs) were injected into the rat model of IVD degeneration. The IVD height, survival, migration, and differentiation of transplanted BMSCs and matrix protein expression (collagen II, aggrecan, and MMP-13) were tested. Results. H-BMSCs could extensively decrease IVD degeneration by increasing IVD height and collagen II and aggrecan expressions when compared with BMSCs. Significantly, more GFP-positive BMSCs were observed in the nucleus pulposus and annulus fibrosus regions of IVD. HP could significantly decrease BMSC apoptosis (activating bcl-2 and inhibiting caspase-3) and improve BMSC migration (increasing HIF-1α and CXCR4) in vitro. Conclusion. HP could significantly enhance the capacity of BMSCs to repair DDD by increasing the survival and migration of implanted cells and increasing matrix protein expression.

scholarly journals Platelet-rich plasma (PRP) and adipose-derived mesenchymal stem cells: stimulatory effects on proliferation and migration of fibroblasts and keratinocytes in vitro

2016 ◽  
Vol 308 (7) ◽  
pp. 511-520 ◽  
Author(s):  
Talita Stessuk ◽  
Maria Beatriz Puzzi ◽  
Elinton Adami Chaim ◽  
Paulo César Martins Alves ◽  
Erich Vinicius de Paula ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Platelet Rich Plasma ◽  
And Migration ◽  
Proliferation And Migration

scholarly journals Pharmacological Inhibition of Gal-3 in Mesenchymal Stem Cells Enhances Their Capacity to Promote Alternative Activation of Macrophages in Dextran Sulphate Sodium-Induced Colitis

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Bojana Simovic Markovic ◽  
Aleksandar Nikolic ◽  
Marina Gazdic ◽  
Jasmin Nurkovic ◽  
Irena Djordjevic ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Peritoneal Macrophages ◽  
Alternative Activation ◽  
Dextran Sulphate ◽  
Dextran Sulphate Sodium ◽  
Pharmacological Inhibition ◽  
And Migration

Transplantation of mesenchymal stem cells (MSCs) reduces the severity of dextran sulphate sodium- (DSS-) induced colitis. MSCs are able to secrete Galectin-3 (Gal-3), a protein known to affect proliferation, adhesion, and migration of immune cells. We investigate whether newly synthetized inhibitor of Gal-3 (Davanat) will affect production of Gal-3 in MSCs and enhance their potential to attenuate DSS-induced colitis. Pharmacological inhibition of Gal-3 in MSCs enhances their capacity to promote alternative activation of peritoneal macrophagesin vitroandin vivo. Injection of MSCs cultured in the presence of Davanat increased concentration of IL-10 in sera of DSS-treated animals and markedly enhanced presence of alternatively activated and IL-10 producing macrophages in the colons of DSS-treated mice. Pharmacological inhibition of Gal-3 in MSCs significantly attenuates concentration of Gal-3 in sera of DSS-treated animals, indicating that MSCs produce Gal-3 in this disease. In conclusion, our findings indicate that Davanat could be used for improvement of MSC-mediated polarization towards immunosuppressive M2 phenotype of macrophages.

scholarly journals Human Glioblastoma-Derived Mesenchymal Stem Cell to Pericytes Transition and Angiogenic Capacity in Glioblastoma Microenvironment

2018 ◽  
Vol 46 (1) ◽  
pp. 279-290 ◽  
Author(s):  
Dongye Yi ◽  
Wei Xiang ◽  
Qing Zhang ◽  
Yongcun Cen ◽  
Qing Su ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Blue Staining ◽  
Alizarin Red ◽  
Differentiation Potential ◽  
And Migration ◽  
Proliferation And Migration ◽  
Vascular Formation

Background/Aims: Tumor vascular formation and maintenance are crucial events in glioblastoma development. Mesenchymal stem cells (MSCs) have been shown to differentiate into pericytes and contribute to neovascularization in the glioma microenvironment. Moreover, glioblastoma-derived mesenchymal stem cells (gb-MSCs), which consist of CD90-MSCs and CD90+MSCs, are a subpopulation of MSCs that are more active in glioma vascularization. However, the functions of gb-MSCs and the microRNA (miRNA) modifications in the glioblastoma microenvironment have not yet been fully elucidated. Here, we focus on the pericyte differentiation potential of gb-MSCs and miRNA modifications in gb-MSCs during new vascular formation and glioblastoma growth. Methods: In vitro, surface markers of gb-MSCs were detected by flow cytometry; the differentiation potential was evaluated by Oil Red O staining, Alizarin Red staining and Alcian blue staining; the proliferation and migration of gb-MSCs in different conditioned media were analyzed by the cck8 test and wound-healing assay, respectively; gb-MSC to pericyte transition was detected by immunofluorescence staining and western blot assay; angiogenetic capacity was analyzed by tube formation assay; and levels of cytokines in different supernatant were determined by ELISA. Additionally, RNA was isolated from gb-MSCs, and miRNA modifications were analyzed using the RAffymetrix miRNA microarray Results: We showed that glioblastoma-conditioned medium increased gb-MSC proliferation and migration and was capable of inducing gb-MSC differentiation into pericytes. Glioblastoma secreted angiogenic factors and gb-MSCs incubated in malignant glioblastoma-conditioned medium formed more tube-like structures, and these cells also adhered to tube-like vessels formed by human umbilical vein endothelial cells (HUVECs) on Matrigel to maintain tumor vascular structure in vitro. miRNA expression were also modified in gb-MSCs cultured in malignant glioblastoma-conditioned medium in vitro. Conclusion: These results provide new insight into the functional effects of a subpopulation of MSCs in glioblastoma and may help in the development of novel therapies for solid tumors.

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