10203 – Method for Biopsy-Free Enrichment and Analysis of Peripheral Blood Mononuclear Cells

  • Methods for the enrichment and analysis of rare circulating HSPCs in blood samples

Abstract

Background & Unmet Need

  • Blood stem cells (HSPCs*) reside in bone marrow, give rise to blood cells, and underlie many hematologic diseases
  • Diagnosis and prognosis of these diseases requires costly and invasive bone marrow biopsies
  • HSPCs are also self-renewing precursors to immune cells, and varied immune response is implicated in inflammatory, autoimmune, and infectious diseases
  • Studies in animal models show that HSPCs can maintain durable epigenetic memory of inflammation and pass it down to their progenitor immune cells
  • The study of altered hematopoiesis and of innate immune memory in humans is challenging due to the invasive nature of acquiring samples of bone marrow, where these stem cells reside
  • Unmet Need: non-invasive acquisition of blood stem cells for diagnosis, prognosis, biomarker and therapy development for inflammatory and hematologic diseases

Technology Overview

  • The Technology: Methods for the enrichment and analysis of rare circulating HSPCs in blood samples
  • The Discovery: While rare (0.05%), HSPCs do circulate in blood and accurately capture the diversity of stem cells that reside in the bone marrow
  • PBMC-PIE (Peripheral Blood Mononuclear Cell analysis with Progenitor Input Enrichment) recapitulates bone marrow HSPC subsets, enables HSPC gene expression analysis, and reveals disease signatures of blood stem cells
  • PBMC-PIE serves as a powerful tool to study hematopoiesis, epigenetic programming of HSPCs, and innate immune memory of inflammation without directly accessing the bone marrow
  • PoC Data: Blood from 112 COVID-19 patients and 47 controls was analyzed using PBMC-PIE coupled with chromatin and expression analysis, enabling detailed single cell profiling of HSPCs and revealing increased myelopoiesis, neutrophil differentiation, and durable epigenetic signatures persisting in HSPCs up to a year post COVID-19

Technology Applications

  • Non-invasive alternative to routine bone marrow biopsy for anemia, leukemia, lymphoma
  • Diagnostic/prognostic assays, and drug target discovery for inflammatory, autoimmune, infectious diseases, post-viral sequelae (e.g., “long COVID”)
  • Signature-based response predictions to vaccinations and cancer immunotherapies
  • Research tool to study HSPC biology, hematopoiesis, immune response to infection, vaccine design
  • “Epigenetic vaccines” that reprogram HSPCs

Technology Advantages

  • Non-invasive, based on a standard blood draw
  • High resolution detection of diverse HSPC subsets
  • Can be combined with single cell assays or high-throughput clinical assays (immunoassay, PCR)
  • Can be scaled up for clinical applications

Publications

  • Cheong et al. “Epigenetic Memory of COVID-19 in Innate Immune Cells and Their Progenitors.” Biorxiv. 2022.

Patents

  • Provisional Filed

Contact Information

Name: Donna Rounds

Email: djr296@cornell.edu

Phone: 646-962-7045