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

2021 ◽  
Vol 95 (2) ◽  
pp. 727-747
Author(s):  
Simone Rothmiller ◽  
Niklas Jäger ◽  
Nicole Meier ◽  
Thimo Meyer ◽  
Adrian Neu ◽  
...  

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.


Nanomaterials ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 779
Author(s):  
Chiara Argentati ◽  
Francesco Morena ◽  
Chiara Fontana ◽  
Ilaria Tortorella ◽  
Carla Emiliani ◽  
...  

The biomedical translational applications of functionalized nanoparticles require comprehensive studies on their effect on human stem cells. Here, we have tested neat star-shaped mesoporous silica nanoparticles (s-MSN) and their chemically functionalized derivates; we examined nanoparticles (NPs) with similar dimensions but different surface chemistry, due to the amino groups grafted on silica nanoparticles (s-MSN-NH2), and gold nanoseeds chemically adsorbed on silica nanoparticles (s-MSN-Au). The different samples were dropped on glass coverslips to obtain a homogeneous deposition differing only for NPs’ chemical functionalization and suitable for long-term culture of human Bone Marrow–Mesenchymal stem cells (hBM-MSCs) and Adipose stem cells (hASCs). Our model allowed us to demonstrate that hBM-MSCs and hASCs have comparable growth curves, viability, and canonical Vinculin Focal adhesion spots on functionalized s-MSN-NH2 and s-MSN-Au as on neat s-MSN and control systems, but also to show morphological changes on all NP types compared to the control counterparts. The new shape was stem-cell-specific and was maintained on all types of NPs. Compared to the other NPs, s-MSN-Au exerted a small genotoxic effect on both stem cell types, which, however, did not affect the stem cell behavior, likely due to a peculiar stem cell metabolic restoration response.



2016 ◽  
Vol 879 ◽  
pp. 2444-2449 ◽  
Author(s):  
Ekaterina Chudinova ◽  
Maria Surmeneva ◽  
Andrey Koptioug ◽  
Irina V. Savintseva ◽  
Irina Selezneva ◽  
...  

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.



2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jianxin Yan ◽  
Jiaji Liang ◽  
Yingxuan Cao ◽  
Mariya M. El Akkawi ◽  
Xuan Liao ◽  
...  

Abstract Background Mesenchymal stem cells (MSCs) exert positive effects in chronic wounds. However, critical parameters, such as the most effective administration routes, remain unclear. Accordingly, the purpose of this study was to compare the effects of topical and systemic transplantation MSCs on diabetic ischemic wound healing and explored the underlying mechanisms. Method A diabetic ischemic wound model was created on the dorsal foot of type 2 diabetes mellitus (T2DM) rat. Bone marrow-derived mesenchymal stem cells (BM-MSCs) were administered via two routes: topical injection and intravenous (IV) infusion. Wound healing outcomes and blood glucose level were assessed dynamically. Meanwhile, blood flow recovery was evaluated in ischemic gastrocnemius muscles. The homing and transdifferentiation of mKate2-labeled BM-MSCs were assessed by fluorescence imaging and immunohistochemistry (IHC) analysis. Result Both topical and systemic treatments had a positive effect on the diabetic ischemic wound showing a significant reduction in wound area at day 14. Histological results showed an increase in the length of epithelial edges, collagen content, microvessel density in the wound bed, and a higher expression of vascular endothelial growth factor (VEGF). Meanwhile, systemic administration can ameliorate hyperglycemia and improve the blood perfusion of the ischemic hindlimb. BM-MSCs administered systemically were found distributed in wounded tissue and transdifferentiated into endothelial cells. Furthermore, BM-MSCs stimulated angiogenesis at wound sites by downregulating phosphatase and tensin homolog (PTEN) and activation of AKT signaling pathway. Conclusions The results demonstrated that both transplantation delivery method (topical and systemic) of BM-MSCs accelerated wound healing remarkably under pathological conditions. Nevertheless, systemic administration has the potential to ameliorate hyperglycemia and repair the damaged tissue.



Injury ◽  
2006 ◽  
Vol 37 (3) ◽  
pp. S33-S42 ◽  
Author(s):  
Lucy DiSilvio ◽  
Jacqueline Jameson ◽  
Zakareya Gamie ◽  
Peter V. Giannoudis ◽  
Eleftherios Tsiridis


2009 ◽  
Vol 181 (4) ◽  
pp. 681
Author(s):  
Gerhard Feil ◽  
Adriana Drost ◽  
Simon Baumann ◽  
Jochen Schäfer ◽  
Sibylle Weng ◽  
...  




2011 ◽  
Vol 43 (2) ◽  
pp. 91-100 ◽  
Author(s):  
Cornelia Hildebrandt ◽  
Heiko Büth ◽  
Hagen Thielecke


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