Impact of Graphene Derivatives as Artificial Extracellular Matrices on Mesenchymal Stem Cells

Thanks to stem cells’ capability to differentiate into multiple cell types, damaged human tissues and organs can be rapidly well-repaired. Therefore, their applicability in the emerging field of regenerative medicine can be further expanded, serving as a promising multifunctional tool for tissue engineering, treatments for various diseases, and other biomedical applications as well. However, the differentiation and survival of the stem cells into specific lineages is crucial to be exclusively controlled. In this frame, growth factors and chemical agents are utilized to stimulate and adjust proliferation and differentiation of the stem cells, although challenges related with degradation, side effects, and high cost should be overcome. Owing to their unique physicochemical and biological properties, graphene-based nanomaterials have been widely used as scaffolds to manipulate stem cell growth and differentiation potential. Herein, we provide the most recent research progress in mesenchymal stem cells (MSCs) growth, differentiation and function utilizing graphene derivatives as extracellular scaffolds. The interaction of graphene derivatives in human and rat MSCs has been also evaluated. Graphene-based nanomaterials are biocompatible, exhibiting a great potential applicability in stem-cell-mediated regenerative medicine as they may promote the behaviour control of the stem cells. Finally, the challenges, prospects and future trends in the field are discussed.

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

Stem Cells International ◽

10.1155/2018/7131532 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 7

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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The Effect of Blood-Derived Products on the Chondrogenic and Osteogenic Differentiation Potential of Adipose-Derived Mesenchymal Stem Cells Originated from Three Different Locations

Stem Cells International ◽

10.1155/2019/1358267 ◽

2019 ◽

Vol 2019 ◽

pp. 1-20 ◽

Cited By ~ 1

Author(s):

Markus Neubauer ◽

Olga Kuten ◽

Christoph Stotter ◽

Karina Kramer ◽

Andrea De Luna ◽

...

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Regenerative Medicine ◽

Blood Product ◽

Blood Products ◽

Fat Tissue ◽

Differentiation Potential ◽

Lower Blood

Background. Adipose-derived mesenchymal stem cells (AD-MSCs) from fat tissue considered “surgical waste” during joint surgery may provide a potent source for regenerative medicine. Intra-articular, homologous fat tissue (Hoffa’s fat pad, pouch fat) might possess a superior chondrogenic and osteogenic differentiation potential in comparison to extra-articular, nonhomologous fat. Blood products might further enhance this potential. Methods. AD-MSCs were isolated from fat tissue of 3 donors from 3 locations each, during total knee replacement. Isolated cells were analyzed via flow cytometry. Cells were supplemented with blood products: two types of platelet-rich plasma (EPRP—PRP prepared in the presence of EDTA; CPRP—PRP prepared in the presence of citrate), hyperacute serum (hypACT), and standard fetal calf serum (FCS) as a positive control. The viability of the cells was determined by XTT assay, and the progress of differentiation was tested via histological staining and monitoring of specific gene expression. Results. Blood products enhance ex vivo cell metabolism. Chondrogenesis is enhanced by EDTA-PRP and osteogenesis by citrate PRP, whereas hyperacute serum enhances both differentiations comparably. This finding was consistent in histological analysis as well as in gene expression. Lower blood product concentrations and shorter differentiation periods lead to superior histological results for chondrogenesis. Both PRP types had a different biological effect depending upon concentration, whereas hyperacute serum seemed to have a more consistent effect, independent of the used concentration. Conclusion. (i) Blood product preparation method, (ii) type of anticoagulant, (iii) differentiation time, and (iv) blood product concentration have a significant influence on stem cell viability and the differentiation potential, favouring no use of anticoagulation, shorter differentiation time, and lower blood product concentrations. Cell-free blood products like hyperacute serum may be considered as an alternative supplementation in regenerative medicine, especially for stem cell therapies.

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Epigenetic Regulation of Mesenchymal Stem Cells: A Focus on Osteogenic and Adipogenic Differentiation

Stem Cells International ◽

10.4061/2011/201371 ◽

2011 ◽

Vol 2011 ◽

pp. 1-18 ◽

Cited By ~ 57

Author(s):

Chad M. Teven ◽

Xing Liu ◽

Ning Hu ◽

Ni Tang ◽

Stephanie H. Kim ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Epigenetic Regulation ◽

Adult Stem Cells ◽

Es Cells ◽

Adipogenic Differentiation ◽

Embryonic Stem ◽

Cell Types ◽

Differentiation Potential ◽

Msc Differentiation

Stem cells are characterized by their capability to self-renew and terminally differentiate into multiple cell types. Somatic or adult stem cells have a finite self-renewal capacity and are lineage-restricted. The use of adult stem cells for therapeutic purposes has been a topic of recent interest given the ethical considerations associated with embryonic stem (ES) cells. Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into osteogenic, adipogenic, chondrogenic, or myogenic lineages. Owing to their ease of isolation and unique characteristics, MSCs have been widely regarded as potential candidates for tissue engineering and repair. While various signaling molecules important to MSC differentiation have been identified, our complete understanding of this process is lacking. Recent investigations focused on the role of epigenetic regulation in lineage-specific differentiation of MSCs have shown that unique patterns of DNA methylation and histone modifications play an important role in the induction of MSC differentiation toward specific lineages. Nevertheless, MSC epigenetic profiles reflect a more restricted differentiation potential as compared to ES cells. Here we review the effect of epigenetic modifications on MSC multipotency and differentiation, with a focus on osteogenic and adipogenic differentiation. We also highlight clinical applications of MSC epigenetics and nuclear reprogramming.

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Human Amniotic Fluid Mesenchymal Stem Cells from Second- and Third-Trimester Amniocentesis: Differentiation Potential, Molecular Signature, and Proteome Analysis

Stem Cells International ◽

10.1155/2015/319238 ◽

2015 ◽

Vol 2015 ◽

pp. 1-15 ◽

Cited By ~ 36

Author(s):

Jurate Savickiene ◽

Grazina Treigyte ◽

Sandra Baronaite ◽

Giedre Valiuliene ◽

Algirdas Kaupinis ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Amniotic Fluid ◽

Expression Patterns ◽

Specific Gene ◽

Specific Cell ◽

Third Trimester ◽

Human Amniotic Fluid ◽

Differentiation Potential

Human amniotic fluid stem cells have become an attractive stem cell source for potential applications in regenerative medicine and tissue engineering. The aim of this study was to characterize amniotic fluid-derived mesenchymal stem cells (AF-MSCs) from second- and third-trimester of gestation. Using two-stage protocol, MSCs were successfully cultured and exhibited typical stem cell morphological, specific cell surface, and pluripotency markers characteristics. AF-MSCs differentiated into adipocytes, osteocytes, chondrocytes, myocytes, and neuronal cells, as determined by morphological changes, cell staining, and RT-qPCR showing the tissue-specific gene presence for differentiated cell lineages. Using SYNAPT G2 High Definition Mass Spectrometry technique approach, we performed for the first time the comparative proteomic analysis between undifferentiated AF-MSCs from late trimester of gestation and differentiated into myogenic, adipogenic, osteogenic, and neurogenic lineages. The analysis of the functional and expression patterns of 250 high abundance proteins selected from more than 1400 demonstrated the similar proteome of cultured and differentiated AF-MSCs but the unique changes in their expression profile during cell differentiation that may help the identification of key markers in differentiated cells. Our results provide evidence that human amniotic fluid of second- and third-trimester contains stem cells with multilineage potential and may be attractive source for clinical applications.

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Abstract 17093: Human Neonatal Cardiac Mesenchymal Stem Cells Demonstrates Superior Cardiac Regenerative Abilities Compared to Other Stem Cells

Circulation ◽

10.1161/circ.142.suppl_3.17093 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Muthukumar Gunasekaran ◽

Rachana Mishra ◽

Progyaparamita Saha ◽

Xuebin Fu ◽

Mohamed Abdullah ◽

...

Keyword(s):

Myocardial Infarction ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Inflammatory Cytokines ◽

Cell Types ◽

Wild Type ◽

Cell Type ◽

Anti Inflammatory ◽

Stem Cell Type

Stem cells transplantation is being explored as an effective therapy for heart diseases. However, majority of stem cell therapies for adult patients with myocardial infarction (MI) had mixed and inconsistent results implying chronological age may influence the effectiveness of regenerative therapies. Therefore, herein, we performed a head-to-head comparison between different, well-studied stem cell types to identify the superior regenerative cell type using rodent MI model.After our standard characterization for each stem cell type (FACS for cell surface markers), 1 million neonatal Cardiac Mesenchymal Stem cells (nMSCs), adult MSCs (aMSCs), adult derived cardiosphere derived cells (aCDCs), umbilical cord derived cells (UCBCs), Bone Marrow derived Mesenchymal Stem cells (BM-MSCs), or cell-free Iscove Modified Dulbecco Medium (IMDM as placebo control) were injected into athymic rat myocardial infarct model. Although all the tested groups significantly improved ejection fraction, nMSCs outperformed other stem cells in cardiac functional recovery. Additionally, nMSCs also showed significant increased cardiac functional recovery compared to aMSCs in wild type rat MI model. Mason trichrome staining with heart sections revealed that decreased fibrosis was evident on nMSCs injection compared to aMSCs in both athymic and wild type rat MI model. Myocardial sections from rats received nMSCs showed significantly reduced M1 macrophages (inflammatory) and increased M2 macrophages (anti-inflammatory) compared with sections from rats having received aMSCs and IMDM control. Pro and anti-inflammatory cytokines analyzed on sera collected on day 2 and 7 revealed that anti-inflammatory cytokine (IL10) was significantly increased and inflammatory cytokines (IL4 and IL12) reduced in nMSCs compared to aMSCs transplanted MI rat model.In conclusion, nMSCs demonstrated superior functional abilities, reduced fibrosis, inflammatory cells and cytokines compared to all the other cell types and with aMSCs demonstrating that nMSCs is an ideal stem cell type for therapeutic application in myocardial infarction.

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CircRNA-vgll3 promotes osteogenic differentiation of adipose-derived mesenchymal stem cells via modulating miRNA-dependent integrin α5 expression

Cell Death and Differentiation ◽

10.1038/s41418-020-0600-6 ◽

2020 ◽

Vol 28 (1) ◽

pp. 283-302

Author(s):

Dandan Zhang ◽

Ni Ni ◽

Yuyao Wang ◽

Zhimin Tang ◽

Huiqin Gao ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Regenerative Medicine ◽

Osteogenic Differentiation ◽

Progenitor Cell ◽

Bone Repair ◽

Circular Rnas ◽

Mineral Density ◽

Differentiation Potential ◽

Integrin Α5

AbstractAdipose-derived mesenchymal stem cells (ADSCs) are promising candidate for regenerative medicine to repair non-healing bone defects due to their high and easy availability. However, the limited osteogenic differentiation potential greatly hinders the clinical application of ADSCs in bone repair. Accumulating evidences demonstrate that circular RNAs (circRNAs) are involved in stem/progenitor cell fate determination, but their specific role in stem/progenitor cell osteogenesis, remains mostly undescribed. Here, we show that circRNA-vgll3 originating from the vgll3 locus markedly enhances osteogenic differentiation of ADSCs; nevertheless, silencing of circRNA-vgll3 dramatically attenuates ADSC osteogenesis. Furthermore, we validate that circRNA-vgll3 functions in ADSC osteogenesis through a circRNA-vgll3/miR-326-5p/integrin α5 (Itga5) pathway. Itga5 promotes ADSC osteogenic differentiation and miR-326-5p suppresses Itga5 translation. CircRNA-vgll3 directly sequesters miR-326-5p in the cytoplasm and inhibits its activity to promote osteogenic differentiation. Moreover, the therapeutic potential of circRNA-vgll3-modified ADSCs with calcium phosphate cement (CPC) scaffolds was systematically evaluated in a critical-sized defect model in rats. Our results demonstrate that circRNA-vgll3 markedly enhances new bone formation with upregulated bone mineral density, bone volume/tissue volume, trabeculae number, and increased new bone generation. This study reveals the important role of circRNA-vgll3 during new bone biogenesis. Thus, circRNA-vgll3 engineered ADSCs may be effective potential therapeutic targets for bone regenerative medicine.

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Novel Nanocomposite PLA Films with Lignin/Zinc Oxide Hybrids: Design, Characterization, Interaction with Mesenchymal Stem Cells

Nanomaterials ◽

10.3390/nano10112176 ◽

2020 ◽

Vol 10 (11) ◽

pp. 2176

Author(s):

Francesca Luzi ◽

Ilaria Tortorella ◽

Alessandro Di Michele ◽

Franco Dominici ◽

Chiara Argentati ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Food Packaging ◽

Biomedical Application ◽

Cell Types ◽

Nanocomposite Films ◽

Diameter Distribution ◽

Filamin A ◽

Stress And Deformation

Herein we present the production of novel nanocomposite films consisting of polylactic acid (PLA) polymer and the inclusion of nanoparticles of lignin (LNP), ZnO and hybrid ZnO@LNP (ZnO, 3.5% wt, ICP), characterized by similar regular shapes and different diameter distribution (30–70 nm and 100–150 nm, respectively). The obtained set of binary, ternary and quaternary systems were similar in surface wettability and morphology but different in the tensile performance: while the presence of LNP and ZnO in PLA caused a reduction of elastic modulus, stress and deformation at break, the inclusion of ZnO@LNP increased the stiffness and tensile strength (σb = 65.9 MPa and EYoung = 3030 MPa) with respect to neat PLA (σb = 37.4 MPa and EYoung = 2280 MPa). Neat and nanocomposite PLA-derived films were suitable for adult human bone marrow-mesenchymal stem cells and adipose stem cell cultures, as showed by their viability and behavior comparable to control conditions. Both stem cell types adhered to the films’ surface by vinculin focal adhesion spots and responded to the films’ mechanical properties by orchestrating the F-actin–filamin A interaction. Collectively, our results support the biomedical application of neat- and nanocomposite-PLA films and, based on the absence of toxicity in seeded stem cells, provide a proof of principle of their safety for food packaging purposes.

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Sources and Clinical Applications of Mesenchymal Stem Cells: State-of-the-art review

Sultan Qaboos University Medical Journal [SQUMJ] ◽

10.18295/squmj.2018.18.03.002 ◽

2018 ◽

Vol 18 (3) ◽

pp. 264 ◽

Cited By ~ 52

Author(s):

Roberto Berebichez-Fridman ◽

Pablo R. Montero-Olvera

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Regenerative Medicine ◽

Adult Stem Cells ◽

Current Knowledge ◽

Clinical Applications ◽

The Body ◽

Differentiation Potential ◽

Advantages And Disadvantages

First discovered by Friedenstein in 1976, mesenchymal stem cells (MSCs) are adult stem cells found throughout the body that share a fixed set of characteristics. Discovered initially in the bone marrow, this cell source is considered the gold standard for clinical research, although various other sources—including adipose tissue, dental pulp, mobilised peripheral blood and birth-derived tissues—have since been identified. Although similar, MSCs derived from different sources possess distinct characteristics, advantages and disadvantages, including their differentiation potential and proliferation capacity, which influence their applicability. Hence, they may be used for specific clinical applications in the fields of regenerative medicine and tissue engineering. This review article summarises current knowledge regarding the various sources, characteristics and therapeutic applications of MSCs.Keywords: Mesenchymal Stem Cells; Adult Stem Cells; Regenerative Medicine; Cell Differentiation; Tissue Engineering.

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Human Mesenchymal Stem Cells Display Reduced Expression of CD105 after Culture in Serum-Free Medium

Stem Cells International ◽

10.1155/2013/698076 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 46

Author(s):

Peter Mark ◽

Mandy Kleinsorge ◽

Ralf Gaebel ◽

Cornelia A. Lux ◽

Anita Toelk ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Ex Vivo ◽

Human Mesenchymal Stem Cells ◽

Cell Types ◽

Growth Media ◽

Clinical Use ◽

Differentiation Potential ◽

Serum Free ◽

The Impact

Human Mesenchymal Stem Cells (hMSCs) present a promising tool for regenerative medicine. However,ex vivoexpansion is necessary to obtain sufficient cells for clinical therapy. Conventional growth media usually contain the critical component fetal bovine serum. For clinical use, chemically defined media will be required. In this study, the capability of two commercial, chemically defined, serum-free hMSC growth media (MSCGM-CD and PowerStem) for hMSC proliferation was examined and compared to serum-containing medium (MSCGM). Immunophenotyping of hMSCs was performed using flow cytometry, and they were tested for their ability to differentiate into a variety of cell types. Although the morphology of hMSCs cultured in the different media differed, immunophenotyping displayed similar marker patterns (high expression of CD29, CD44, CD73, and CD90 cell surface markers and absence of CD45). Interestingly, the expression of CD105 was significantly lower for hMSCs cultured in MSCGM-CD compared to MSCGM. Both groups maintained mesenchymal multilineage differentiation potential. In conclusion, the serum-free growth medium is suitable for hMSC culture and comparable to its serum-containing counterpart. As the expression of CD105 has been shown to positively influence hMSC cardiac regenerative potential, the impact of CD105 expression onto clinical use after expansion in MSCGM-CD will have to be tested.

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Mesenchymal Stem Cells Isolated from Adipose and Other Tissues: Basic Biological Properties and Clinical Applications

Stem Cells International ◽

10.1155/2012/461718 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 100

Author(s):

Hakan Orbay ◽

Morikuni Tobita ◽

Hiroshi Mizuno

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adult Stem Cells ◽

Cell Types ◽

Biological Properties ◽

Clinical Applications ◽

Therapeutic Tool ◽

Adult Tissues ◽

Clinical Benefits ◽

Multiple Cell

Mesenchymal stem cells (MSCs) are adult stem cells that were initially isolated from bone marrow. However, subsequent research has shown that other adult tissues also contain MSCs. MSCs originate from mesenchyme, which is embryonic tissue derived from the mesoderm. These cells actively proliferate, giving rise to new cells in some tissues, but remain quiescent in others. MSCs are capable of differentiating into multiple cell types including adipocytes, chondrocytes, osteocytes, and cardiomyocytes. Isolation and induction of these cells could provide a new therapeutic tool for replacing damaged or lost adult tissues. However, the biological properties and use of stem cells in a clinical setting must be well established before significant clinical benefits are obtained. This paper summarizes data on the biological properties of MSCs and discusses current and potential clinical applications.

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