The influence of tantalum on human cell lineages important for healing in soft-tissue reattachment surgery: an in-vitro analysis

Abstract Background Porous tantalum is currently used in orthopaedic surgery for a variety of indications including soft tissue re-attachment. However, the clinical results have been variable and a previous laboratory study has suggested that tantalum may actually inhibit chick tendon fibroblasts. The influence of tantalum on human cell-types involved in soft tissue re-attachment has not been defined. Methods Human fibroblasts, human osteoblasts and human mesenchymal stem cells were plated on glass cover slips, half of which were coated with tantalum. Cell numbers were assessed at 1, 2, 7 and 14 days using Cyquant® assay. Cell adhesion and morphology were assessed using light microscopy at 7, 14 and 28 days. To reduce the effect of an expected rate of error, n = 4 was utilised for each cell type and the experiment was repeated twice. Results Statistically similar numbers of human osteoblasts and human mesenchymal stem cells were present at 14 days on tantalum-coated and uncoated glass cover slips, revealing no inhibitory effect on cell proliferation. More than double the number of human fibroblasts was seen on tantalum-coated cover slips at that time point (compared to controls), which was statistically significant (p < 0.0001). Morphological assessment revealed normal cell spreading and adhesion on both substrates at all time points. Conclusions In vitro study demonstrates that Tantalum causes a significant increase in the proliferation of human fibroblasts with no quantifiable negative effects seen on fibroblast behaviour after 28 days culture. Furthermore, tantalum does not exert any inhibitory effects on the proliferation or behaviour of human osteoblasts or human mesenchymal stem cells. Tantalum could be an appropriate biomaterial for use in situations where soft tissue requires direct reattachment to implants and may stimulate soft tissue healing.

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In vitro evaluation of the direct effect of estradiol on human osteoblasts (HOB) and human mesenchymal stem cells (h-MSCs)

Injury ◽

10.1016/j.injury.2006.08.022 ◽

2006 ◽

Vol 37 (3) ◽

pp. S33-S42 ◽

Cited By ~ 29

Author(s):

Lucy DiSilvio ◽

Jacqueline Jameson ◽

Zakareya Gamie ◽

Peter V. Giannoudis ◽

Eleftherios Tsiridis

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Direct Effect ◽

Human Mesenchymal Stem Cells ◽

Human Osteoblasts ◽

In Vitro Evaluation

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Electrical signature of heterogeneous human mesenchymal stem cells

10.1101/2021.11.08.467665 ◽

2021 ◽

Author(s):

Tunglin Tsau ◽

Prema Vyas ◽

Lexi Crowell ◽

Mary Tran ◽

Destiney Ward ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Human Fibroblasts ◽

Human Mesenchymal Stem Cells ◽

Label Free ◽

Differentiation Potential ◽

Hek 293 ◽

Human Embryonic Kidney Cells

Human mesenchymal stem cells (hMSCs) have gained traction in transplantation therapy due to their immunomodulatory, paracrine, immune-evasive, and multipotent differentiation potential. Given the heterogeneous nature of hMSCs, therapeutic treatments and robust in vivo and in vitro experiments require additional biomarkers to ensure reproducibility when using these stem cells. In this work, we utilized dielectrophoresis (DEP), a label-free electrokinetic phenomenon, to investigate and quantify the heterogeneity of hMSCs derived from the bone marrow (BM) and adipose tissue (AD). Through computer simulation, we identified that the transient slope of the DEP force spectra can be used as a metric of heterogeneity. The electrical properties of BM-hMSCs were compared to homogeneous mouse fibroblasts (NIH-3T3), human fibroblasts (WS1), and human embryonic kidney cells (HEK-293). BM-hMSCs DEP profile was most different from HEK-293 cells. We compared the DEP profiles of BM-hMSCs and AD-hMSCs and found they have similar membrane capacitances, differing cytoplasm conductivity, and transient slopes. Inducing both populations to differentiate into adipocyte and osteocyte cells revealed they behave differently in response to differentiation-inducing cytokines. Histology and RT-qPCR analyses of the differentiation-related genes revealed differences in heterogeneity between BM-hMSCs and AD-hMSCs. The differentiation profiles correlate well with the DEP profiles developed and indicate that these BM-hMSCs have higher differentiation potential than AD-hMSCs. Our results demonstrate using DEP, membrane capacitance, cytoplasm conductivity, and transient slope can uniquely characterize the inherent heterogeneity of hMSCs to guide robust and reproducible stem cell transplantation therapies.

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NAD+/NADH redox alterations reconfigure metabolism and rejuvenate senescent human mesenchymal stem cells in vitro

Communications Biology ◽

10.1038/s42003-020-01514-y ◽

2020 ◽

Vol 3 (1) ◽

Author(s):

Xuegang Yuan ◽

Yijun Liu ◽

Brent M. Bijonowski ◽

Ang-Chen Tsai ◽

Qin Fu ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adult Stem Cells ◽

Replicative Senescence ◽

Human Fibroblasts ◽

Human Mesenchymal Stem Cells ◽

Redox Balance ◽

Rapid Decline ◽

Nadh Ratio

AbstractHuman mesenchymal stem cells (hMSCs) promote endogenous tissue regeneration and have become a promising candidate for cell therapy. However, in vitro culture expansion of hMSCs induces a rapid decline of stem cell properties through replicative senescence. Here, we characterize metabolic profiles of hMSCs during expansion. We show that alterations of cellular nicotinamide adenine dinucleotide (NAD + /NADH) redox balance and activity of the Sirtuin (Sirt) family enzymes regulate cellular senescence of hMSCs. Treatment with NAD + precursor nicotinamide increases the intracellular NAD + level and re-balances the NAD + /NADH ratio, with enhanced Sirt-1 activity in hMSCs at high passage, partially restores mitochondrial fitness and rejuvenates senescent hMSCs. By contrast, human fibroblasts exhibit limited senescence as their cellular NAD + /NADH balance is comparatively stable during expansion. These results indicate a potential metabolic and redox connection to replicative senescence in adult stem cells and identify NAD + as a metabolic regulator that distinguishes stem cells from mature cells. This study also suggests potential strategies to maintain cellular homeostasis of hMSCs in clinical applications.

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Faculty Opinions recommendation of Expression of the p16INK4A gene is associated closely with senescence of human mesenchymal stem cells and is potentially silenced by DNA methylation during in vitro expansion.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1088258.541282 ◽

2007 ◽

Author(s):

Helen Gruber

Keyword(s):

Dna Methylation ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Human Mesenchymal Stem Cells ◽

P16ink4a Gene ◽

In Vitro Expansion

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Faculty Opinions recommendation of Proliferation as a requirement for in vitro chondrogenesis of human mesenchymal stem cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717960004.793463156 ◽

2012 ◽

Author(s):

David Lee ◽

Stephen Thorpe

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Human Mesenchymal Stem Cells

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In Vitro Assessment of Hydroxyapatite Coating on the Surface of Additive Manufactured Ti6Al4V Scaffolds

Materials Science Forum ◽

10.4028/www.scientific.net/msf.879.2444 ◽

2016 ◽

Vol 879 ◽

pp. 2444-2449 ◽

Cited By ~ 1

Author(s):

Ekaterina Chudinova ◽

Maria Surmeneva ◽

Andrey Koptioug ◽

Irina V. Savintseva ◽

Irina Selezneva ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Human Mesenchymal Stem Cells ◽

Nanocrystalline Structure ◽

X Ray Diffraction ◽

Ha Coating ◽

Magnetron Sputter Deposition ◽

In Vitro Assessment ◽

Average Size

Custom orthopedic and dental implants may be fabricated by additive manufacturing (AM), for example using electron beam melting technology. This study is focused on the modification of the surface of Ti6Al4V alloy coin-like scaffolds fabricated via AM technology (EBM®) by radio frequency (RF) magnetron sputter deposition of hydroxyapatite (HA) coating. The scaffolds with HA coating were characterized by Scanning Electron microscopy, X-ray diffraction. HA coating showed a nanocrystalline structure with the crystallites of an average size of 32±9 nm. The ability of the surface to support adhesion and the proliferation of human mesenchymal stem cells was studied using biological short-term tests in vitro. In according to in vitro assessment, thin HA coating stimulated the attachment and proliferation of cells. Human mesenchymal stem cells cultured on the HA-coated scaffold also formed mineralized nodules.

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Chronic senescent human mesenchymal stem cells as possible contributor to the wound healing disorder after exposure to the alkylating agent sulfur mustard

Archives of Toxicology ◽

10.1007/s00204-020-02946-5 ◽

2021 ◽

Vol 95 (2) ◽

pp. 727-747

Author(s):

Simone Rothmiller ◽

Niklas Jäger ◽

Nicole Meier ◽

Thimo Meyer ◽

Adrian Neu ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Alkylating Agent ◽

Chronic Wounds ◽

Sulfur Mustard ◽

Morphological Changes ◽

Human Mesenchymal Stem Cells ◽

Age Related

AbstractWound healing is a complex process, and disturbance of even a single mechanism can result in chronic ulcers developing after exposure to the alkylating agent sulfur mustard (SM). A possible contributor may be SM-induced chronic senescent mesenchymal stem cells (MSCs), unable to fulfil their regenerative role, by persisting over long time periods and creating a proinflammatory microenvironment. Here we show that senescence induction in human bone marrow derived MSCs was time- and concentration-dependent, and chronic senescence could be verified 3 weeks after exposure to between 10 and 40 µM SM. Morphological changes, reduced clonogenic and migration potential, longer scratch closure times, differences in senescence, motility and DNA damage response associated genes as well as increased levels of proinflammatory cytokines were revealed. Selective removal of these cells by senolytic drugs, in which ABT-263 showed initial potential in vitro, opens the possibility for an innovative treatment strategy for chronic wounds, but also tumors and age-related diseases.

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