Scientists use nanotechnology to detect bone-healing stem cells

Stem cells with launch of fluorescent oligonucleotides in purple. Credit score: College of Southampton

Researchers on the College of Southampton have developed a brand new approach of utilizing nanomaterials to establish and enrich skeletal stem cells—a discovery which may finally result in new therapies for main bone fractures and the restore of misplaced or broken bone.


Working collectively, a workforce of physicists, chemists and tissue engineering consultants used specifically designed gold nanoparticles to ‘hunt down’ particular human bone stem cells—making a fluorescent glow to disclose their presence amongst different sorts of cells and permit them to be remoted or ‘enriched’.

The researchers concluded their new method is easier and faster than different strategies and as much as 50-500 instances simpler at enriching stem cells.

The research, led by Professor of Musculoskeletal Science, Richard Oreffo and Professor Antonios Kanaras of the Quantum, Mild and Matter Group within the College of Physics and Astronomy, is printed in ACS Nano—an internationally acknowledged multidisciplinary journal.

In laboratory checks, the researchers used gold nanoparticles—tiny spherical particles made up of hundreds of gold atoms—coated with oligonucleotides (strands of DNA), to optically detect the precise messenger RNA (mRNA) signatures of skeletal stem cells in bone marrow. When detection takes place, the nanoparticles launch a fluorescent dye, making the stem cells distinguishable from different surrounding cells, underneath microscopic remark. The stem cells can then be separated utilizing a classy fluorescence cell sorting course of.

Stem cells are cells that aren’t but specialised and may develop to carry out completely different features. Figuring out skeletal stems cells permits scientists to develop these cells in outlined situations to allow the expansion and formation of bone and cartilage tissue—for instance, to assist mend damaged bones.

Among the many challenges posed by our ageing inhabitants is the necessity for novel and cost-effective approaches to bone restore. With one in three ladies and one in 5 males liable to osteoporotic fractures worldwide, the prices are important, with bone fractures alone costing the European financial system €17 billion and the US financial system $20 billion yearly.

Throughout the College of Southampton’s Bone and Joint Analysis Group, Professor Richard Oreffo and his workforce have been bone stem cell based mostly therapies for over 15 years to know bone tissue improvement and to generate bone and cartilage. Over the identical time-period, Professor Antonios Kanaras and his colleagues within the Quantum, Mild and Matter Group have been designing novel nanomaterials and finding out their functions within the fields of biomedical sciences and power. This newest research successfully brings these disciplines collectively and is an exemplar of the impression collaborative, interdisciplinary working can convey.

Professor Oreffo stated: “Skeletal stem cell based mostly therapies supply among the most enjoyable and promising areas for bone illness therapy and bone regenerative drugs for an ageing inhabitants. The present research have harnessed distinctive DNA sequences from targets we imagine would enrich the skeletal stem cell and, utilizing Fluorescence Activated Cell Sorting (FACS) now we have been in a position to enrich bone stem cells from sufferers. Identification of distinctive markers is the holy grail in bone stem cell biology and, whereas we nonetheless have some technique to go; these research supply a step change in our capability to focus on and establish human bone stem cells and the thrilling therapeutic potential therein.”

Professor Oreffo added: “Importantly, these research present some great benefits of interdisciplinary analysis to handle a difficult drawback with state-of-the-art molecular/cell biology mixed with nanomaterials’ chemistry platform applied sciences.”

Professor Kanaras stated: “The suitable design of supplies is crucial for his or her software in complicated methods. Customizing the chemistry of nanoparticles we’re in a position to program particular features of their design.

“On this analysis venture, we designed nanoparticles coated with brief sequences of DNA, that are in a position to sense HSPA8 mRNA and Runx2 mRNA in skeletal stem cells and along with superior FACS gating methods, to allow the assortment of the related cells from human bone marrow.

“An vital facet of the nanomaterial design entails methods to control the density of oligonucleotides on the floor of the nanoparticles, which assist to keep away from DNA enzymatic degradation in cells. Fluorescent reporters on the oligonucleotides allow us to watch the standing of the nanoparticles at completely different levels of the experiment, guaranteeing the standard of the endocellular sensor.”

Each lead researchers additionally acknowledge that the accomplishments had been doable as a result of work of all of the skilled analysis fellows and Ph.D. college students concerned on this analysis in addition to collaboration with Professor Tom Brown and Dr. Afaf E-Sagheer of the College of Oxford, who synthesized a big number of practical oligonucleotides.

The scientists are at the moment making use of single cell RNA sequencing to the platform expertise developed with companions in Oxford and the Institute for Life Sciences (IfLS) at Southampton to additional refine and enrich bone stem cells and assess performance. The workforce suggest to then transfer to scientific software with preclinical bone formation research to generate proof of idea research.



Extra info:
Miguel Xavier et al, Enrichment of Skeletal Stem Cells from Human Bone Marrow Utilizing Spherical Nucleic Acids, ACS Nano (2021). DOI: 10.1021/acsnano.0c10683

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