scholarly journals Blowup of Accidental Images as a Passageway to Discovery: Insights into the Interaction between Hydroxyapatite Nanoparticles and Human Mesenchymal Stem Cells

2020 ◽  
Vol 10 (22) ◽  
pp. 8204
Author(s):  
Vuk Uskoković

Despite decades of research into the interaction between cells and nanoparticles, there is a lack of consensus regarding how specific physicochemical characteristics of the nanoparticles, including chemical composition, crystallinity, size, morphology, charge, and aspect ratio, among others, govern their internalization and intracellular fate. Methodological novelties offer new perspectives on the same old problematics, and often translate into an improved understanding of the given topic. Inspired by an analogy with the theme of the movie, Lisbon Story, a conceptually unconventional method for gaining insight into the interaction between nanoparticles and cells is proposed here. It involves the random, “Take 1” capture of an atomic force micrograph showing the interaction of human mesenchymal stem cells and clusters of spherical hydroxyapatite nanoparticles with a broad distribution of sizes and shapes, the blowup of its segments, and their detailed qualitative inspection. This method led to the derivation of three illustrative hypotheses, some of which were refuted and some corroborated. Specifically, the presupposition that there is an inverse relationship between the cellular uptake efficiency and the size of nanoparticle clusters was confirmed, both empirically and through a literature meta-analysis, but the idea that the geometry of these clusters affects the uptake was refuted. The definite presence of morphological determinants of the cellular uptake at the level of elementary particles, not clusters thereof, however, was confirmed in an alternative experiment. Likewise, immunofluorescent studies demonstrated that relatively large and irregularly shaped nanoparticle clusters do get internalized and localized to the perinuclear area, where they engage in an intimate interaction with the cell nucleus. The proposed enhancement of the binding between cells and biomaterials by increasing the surface ruffling consequential to the nanoparticle uptake - in analogy with the enhanced cell adhesion achieved by introducing topographic irregularities to smooth biomaterial surfaces - was also confirmed by showing that the uptake improves the stem cell adhesion. The uptake also augmented the stem cell viability and the proliferative capacity of cells reseeded with this internal nanoparticle cargo on a fresh surface, albeit with moderate levels of statistical significance and the caveat of its presumed dependence on the cell type, the nanoparticle chemistry and dose, and the overall stage in the transition of the multipotent cells toward an osteoprogenitor lineage.

Genes ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 909
Author(s):  
Eva Bianconi ◽  
Raffaella Casadei ◽  
Flavia Frabetti ◽  
Carlo Ventura ◽  
Federica Facchin ◽  
...  

In humans, sexual dimorphism can manifest in many ways and it is widely studied in several knowledge fields. It is increasing the evidence that also cells differ according to sex, a correlation still little studied and poorly considered when cells are used in scientific research. Specifically, our interest is on the sex-related dimorphism on the human mesenchymal stem cells (hMSCs) transcriptome. A systematic meta-analysis of hMSC microarrays was performed by using the Transcriptome Mapper (TRAM) software. This bioinformatic tool was used to integrate and normalize datasets from multiple sources and allowed us to highlight chromosomal segments and genes differently expressed in hMSCs derived from adipose tissue (hADSCs) of male and female donors. Chromosomal segments and differentially expressed genes in male and female hADSCs resulted to be related to several processes as inflammation, adipogenic and neurogenic differentiation and cell communication. Obtained results lead us to hypothesize that the donor sex of hADSCs is a variable influencing a wide range of stem cell biologic processes. We believe that it should be considered in biologic research and stem cell therapy.


2019 ◽  
Vol 26 (10) ◽  
pp. 785-791
Author(s):  
Ji-Eun Kim ◽  
Hye-Jin Seo ◽  
SuJin Lee ◽  
Jun-Hyeog Jang

Background: Laminin, a member of the Extracellular Matrix (ECM), is a glycoprotein that is used as a factor that affects cell adhesion, proliferation, survival, and differentiation. Of these, five globular domains (LG domains) of the alpha chain play an important role in influencing the cell by binding to the integrin. Objective: This study aimed to evaluate the ability of globular domains 1-3 of laminin alpha2 (rhLAMA2LG1-3) in maintaining the pluripotency of human Mesenchymal Stem Cells (hMSCs), which are widely used in regenerative medicine. Methods: hMSCs were grown in the medium supplemented with rhLAMA2LG1-3, then the effect of the protein on hMSCs were confirmed through cell adhesion assay, proliferation assay and RTPCR. Results: rhLAMA2LG1-3 expressed in Escherichia coli has a molecular weight of 70 kDa, at 1 µg/ml concentration of rhLAMA2LG1-3, the attachment and proliferation of hMSCs were approximately 3.18-fold and 1.67-fold, respectively, more efficient than those of untreated controls. In addition, the undifferentiated state and degree of stemness of hMSCs were measured, on the basis of CD90 and CD105 levels. In the rhLAMA2LG1-3-treated hMSCs, the expression levels of CD90 and CD105 increased by 2.83-fold and 1.62-fold, respectively, compared to those in untreated controls. Conclusion: rhLAMA2LG1-3 can be potentially used in stem cell therapy to improve the viability and maintain the undifferentiated state of hMSCs.


Proceedings ◽  
2018 ◽  
Vol 2 (25) ◽  
pp. 1592
Author(s):  
Sevil Özer ◽  
H. Seda Vatansever ◽  
Feyzan Özdal-Kurt

Bone marrow mesenchymal stem cells (BM-MSCs) are used to repair hypoxic or ischemic tissue. After hypoxic the level of ATP is decreases, cellular functions do not continue and apoptosis or necrosis occur. Apoptosis is a progress of programmed cell death that occurs in normal or pathological conditions. In this study, we were investigated the hypoxic effect on apoptosis in mesenchymal stem cell. Bone marrow-derived stem cells were cultured in hypoxic (1% or 3%) or normoxic conditions 24, 96 well plates for 36 h. Cell viability was shown by MTT assay on 36 h. After fixation of cells with 4% paraformaldehyde, distributions of caspase-3, Bcl-2 and Bax with indirect immunoperoxidase technique, apoptotic cells with TUNEL assay were investigated. All staining results were evaluated using H-score analyses method with ANOVA, statistically. As a result, hypoxic condition was toxic for human mesenchymal stem cells and the number of death cell was higher in that than normoxic condition.


2015 ◽  
Vol 3 (16) ◽  
pp. 3150-3168 ◽  
Author(s):  
Sunil Kumar Boda ◽  
Greeshma Thrivikraman ◽  
Bikramjit Basu

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


2020 ◽  
Vol 56 (20) ◽  
pp. 3043-3046 ◽  
Author(s):  
Swati Sharma ◽  
Chirag Kulkarni ◽  
Manish M. Kulkarni ◽  
Rafat Ali ◽  
Konica Porwal ◽  
...  

We demonstrate the ability of two tripeptides to promote proliferation and modulate the mechanical properties of human mesenchymal stem cells (hMSCs).


2019 ◽  
Vol 55 (6) ◽  
pp. 1029-1040 ◽  
Author(s):  
Xiuxiu Yin ◽  
Linping Hu ◽  
Yawen Zhang ◽  
Caiying Zhu ◽  
Hui Cheng ◽  
...  

AbstractThe bone marrow (BM) niche regulates multiple hematopoietic stem cell (HSC) processes. Clinical treatment for hematological malignancies by HSC transplantation often requires preconditioning via total body irradiation, which severely and irreversibly impairs the BM niche and HSC regeneration. Novel strategies are needed to enhance HSC regeneration in irradiated BM. We compared the effects of EGF, FGF2, and PDGFB on HSC regeneration using human mesenchymal stem cells (MSCs) that were transduced with these factors via lentiviral vectors. Among the above niche factors tested, MSCs transduced with PDGFB (PDGFB-MSCs) most significantly improved human HSC engraftment in immunodeficient mice. PDGFB-MSC-treated BM enhanced transplanted human HSC self-renewal in secondary transplantations more efficiently than GFP-transduced MSCs (GFP-MSCs). Gene set enrichment analysis showed increased antiapoptotic signaling in PDGFB-MSCs compared with GFP-MSCs. PDGFB-MSCs exhibited enhanced survival and expansion after transplantation, resulting in an enlarged humanized niche cell pool that provide a better humanized microenvironment to facilitate superior engraftment and proliferation of human hematopoietic cells. Our studies demonstrate the efficacy of PDGFB-MSCs in supporting human HSC engraftment.


2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Sung Keun Kang ◽  
Il Seob Shin ◽  
Myung Soon Ko ◽  
Jung Youn Jo ◽  
Jeong Chan Ra

Human mesenchymal stem cells (MSCs) communicate with other cells in the human body and appear to “home” to areas of injury in response to signals of cellular damage, known as homing signals. This review of the state of current research on homing of MSCs suggests that favorable cellular conditions and thein vivoenvironment facilitate and are required for the migration of MSCs to the site of insult or injuryin vivo. We review the current understanding of MSC migration and discuss strategies for enhancing both the environmental and cellular conditions that give rise to effective homing of MSCs. This may allow MSCs to quickly find and migrate to injured tissues, where they may best exert clinical benefits resulting from improved homing and the presence of increased numbers of MSCs.


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