Enrichment of Skeletal Stem Cells from Human Bone Marrow Using Spherical Nucleic Acids

Abstract

There 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.

Single cell RNA sequence analysis of human bone marrow samples reveals new targets for isolation of skeletal stem cells using DNA-coated gold nanoparticles

“…Critically, the nanoparticles can be tailored to enhance selectivity and specificity towards the detection of intracellular targets such as RNA. We have recently developed a protocol using AuNPs to rapidly isolate human cells enriched in SSCs without affecting long-term cell viability [8], which has now been used in 80 different patient marrow samples.…”