Gold nanoparticles designed to seek out and isolate human bone stem cells

Researchers have developed a new way of using nanomaterials to identify and enrich skeletal stem cells – a discovery which could eventually lead to new treatments for major bone fractures and the repair of lost or damaged bone. The study was conducted at the University of Southampton, UK. 

The team used specially designed gold nanoparticles to ‘seek out’ specific human bone stem cells – creating a fluorescent glow to reveal their presence among other types of cells and allow them to be isolated or ‘enriched’. The researchers say their new technique is simpler and quicker than other methods and up to 50-500 times more effective at enriching cells.

In laboratory tests, the researchers used gold nanoparticles coated with oligonucleotides to optically detect the specific messenger RNA (mRNA) signatures of skeletal stem cells in bone marrow. When detection takes place, the nanoparticles release a fluorescent dye, making the stem cells distinguishable from other surrounding cells, under microscopic observation. The stem cells can then be separated using a sophisticated fluorescence cell sorting process.

Identifying skeletal stems cells allows scientists to grow these cells in defined conditions to enable the growth and formation of bone and cartilage tissue – for example, to help mend broken bones.

“Skeletal stem cell-based therapies offer some of the most exciting and promising areas for bone disease treatment and bone regenerative medicine for an ageing population. The current studies have harnessed unique DNA sequences from targets we believe would enrich the skeletal stem cell and using Fluorescence Activated Cell Sorting (FACS) we have been able to enrich bone stem cells from patients. Identification of unique markers is the holy grail in bone stem cell biology and while we still have some way to go, these studies offer a step change in our ability to target and identify human bone stem cells and the exciting therapeutic potential therein,” said Professor Richard Oreffo, of of the lead researchers. 

Professor Antonios Kanaras, another of the lead researchers, added: “The appropriate design of materials is essential for their application in complex systems. Customising the chemistry of nanoparticles we are able to program specific functions in their design. In this research project, we designed nanoparticles coated with short sequences of DNA, which are able to sense HSPA8 mRNA and Runx2 mRNA in skeletal stem cells and together with advanced FACS gating strategies, to enable the assortment of the relevant cells from human bone marrow. An important aspect of the nanomaterial design involves strategies to regulate the density of oligonucleotides on the surface of the nanoparticles, which help to avoid DNA enzymatic degradation in cells. Fluorescent reporters on the oligonucleotides enable us to observe the status of the nanoparticles at different stages of the experiment, ensuring the quality of the endocellular sensor.”

The scientists are currently applying single cell RNA sequencing to further refine and enrich bone stem cells and assess functionality. The team propose to then move to clinical application with pre-clinical bone formation studies to generate proof-of-concept studies.

The study is published in ACS Nano.