scholarly journals Optimising DNA-Coated Gold Nanoparticles to Enrich Skeletal Stem Cells from Human Bone Marrow Samples

2019 ◽  
Author(s):  
S.A. Lanham ◽  
M. Xavier ◽  
M.E. Kyriazi ◽  
K. Alexaki ◽  
A.H. El-Sagheer ◽  
...  

AbstractThere is a wealth of data indicating human bone marrow derived stromal cells (HBMSCs) contain the skeletal stem cell (SSC) with the potential to differentiate along the osteogenic, adipogenic and chondrogenic lineages leading to significant interest as potential clinical therapies. However, despite these advances, current methods to isolate skeletal stem cells (SSCs) from human tissues are difficult as no single specific marker has been identified. Hence, limited understanding of SSC fate, immuno-phenotype and simple selection criteria proved to be limiting factors in the widespread clinical application of these cells. While a range of cell surface markers can enrich for SSCs, none of the proposed markers, alone, isolate single cells with the ability to form bone, cartilage, and adipose tissue in humans. In this work, we have developed a methodology to use oligonucleotide-coated gold nanoparticles to identify cells in human bone marrow displaying specific mRNA signatures to isolate and enrich for the SSCs.

2020 ◽  
Author(s):  
Elloise Matthews ◽  
Stuart Lanham ◽  
Kate White ◽  
Maria-Eleni Kyriazi ◽  
Konstantina Alexaki ◽  
...  

AbstractThere is a wealth of data indicating human bone marrow derived stromal cells (HBMSCs) contain the skeletal stem cell (SSC) with the potential to differentiate along the stromal osteogenic, adipogenic and chondrogenic lineages. However, despite these advances, current methods to isolate skeletal stem cells (SSCs) from human tissues have proved challenging as no single specific marker has been identified limiting understanding of SSC fate, immunophenotype and the widespread clinical application of these cells. While a number of cell surface markers can enrich for SSCs, none of the proposed markers, alone, provide a platform to isolate single cells with the ability to form bone, cartilage, and adipose tissue in humans. The current study details the application of oligonucleotide-coated nanoparticles, spherical nucleic acids (SNAs), to rapidly isolate human cells using mRNAs signatures detected in SSCs in real time, to identify stem and progenitor skeletal populations using single cell RNA sequencing. Based on scRNA-seq of samples from 11 patients, this method was able to identify novel targets for SSC enrichment, which were assessed in a total of 80 patients. This methodology was able to isolate potential SSCs found at a frequency of <1 in 1,000,000 in human bone marrow, with a capacity for tri-lineage differentiation in vitro. The current approach provides new targets and a platform to advance SSC isolation, enrichment with significant therapeutic impact therein.


2011 ◽  
Vol 23 (02) ◽  
pp. 141-152 ◽  
Author(s):  
Jui-Hung Fan ◽  
Wen-Tyng Li ◽  
Wei-I Hung ◽  
Cheng-Pao Chen ◽  
Jui-Ming Yeh

Gold nanoparticles (GNPs) are widely used in chemical sensing, drug delivery, biomedical imaging, and photothermal therapy due to their strong and size-tunable surface plasmon resonance, fluorescence, and easy-surface functionalization. In this study, we investigated the effects of water-dispersed GNPs on the cytotoxicity and differentiation of human bone marrow mesenchymal stem cells (hBMSCs) and the associated death pathway. The results showed that the viability of hBMSCs was dependent upon the size of GNPs. Further, GNPs at the smallest size exhibited the highest cytotoxicity after treatment for 5 days and also substantially suppressed the number of colony-forming unit-fibroblast (CFU-F) of hBMSCs after continuous exposure for 21 days. Although large and medium sizes of GNPs had minor cytotoxicity to the cells, the sizes of CFU-F formed in the groups treated with GNPs at medium and large sizes were smaller compared to the control group. Further study of the cell death pathway using GNPs at medium size found that GNPs triggered hBMSCs necrosis, possibly by oxidative stress after GNPs were endocytosed. In addition, GNPs exerted the inhibitory effects on induced osteogenesis and adipogenesis of hBMSCs. Alkaline phosphatase (ALP) activity and calcium mineralization during osteogenic induction as well as the accumulation of triacylglycerides in adipogenic hBMSCs were repressed significantly by coculturing with GNPs at medium size. Our results suggest that the application of GNPs as long-term tracers for the activities of mesenchymal stem cells (MSCs) should be carefully evaluated.


2015 ◽  
Vol 208 ◽  
pp. S100-S101
Author(s):  
Gamze Tan ◽  
Melek Yaman ◽  
Nihan Örüklü ◽  
Necdet Sağlam ◽  
Emin Ümit Bağrıaçık

2021 ◽  
Author(s):  
Xia Yi ◽  
Ping Wu ◽  
Jianyun Liu ◽  
Shan He ◽  
Ying Gong ◽  
...  

Adipogenesis and osteoblastogenesis (adipo-osteoblastogenesis) are closely related processes involving with the phosphorylation of numerous cytoplasmic proteins and key transcription factors.


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