Rare Circulating Cell Enrichment from Peripheral Blood
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Solution Overview
Problem
Current methods for obtaining hematopoietic stem and progenitor cells (HSPC) are invasive, costly, and limited, particularly for diagnosing and treating diseases related to inflammation and COVID-19, where non-invasive acquisition of stem cells from peripheral blood is needed to characterize disease states and measure therapeutic efficacy.
Innovation Solution
A method for characterizing cellular molecular features and functional characteristics of rare circulating cells from peripheral blood, involving the enrichment of these cells, acquisition of transcriptomic, genetic, and protein expression data, and analysis to generate transcriptional, genetic, protein, metabolic, epigenomic, and functional characteristic signatures.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If stem cells are obtained from bone marrow, then the quality and quantity of HSPC are improved, but the invasiveness and complexity of the procedure worsen
Solution Approach 1:
The patent extracts HSPC from peripheral blood mononuclear cells (PBMC) rather than obtaining them directly from bone marrow. This involves isolating PBMC from peripheral blood and then enriching for HSPC within that population, thereby avoiding the invasive bone marrow aspiration procedure while still obtaining the desired stem cells.
Solution Approach 2:
The patent uses peripheral blood mononuclear cells (PBMC) as an intermediary population to access HSPC. Instead of directly harvesting from bone marrow, the method first obtains PBMC from peripheral blood (a less invasive source) and then enriches for the HSPC subset within that intermediate population.
2Ease of operation
If stem cells are obtained from peripheral blood, then the ease of acquisition is improved, but the quantity and quality of HSPC worsen
Solution Approach 1:
The patent employs parameter changes in the form of enrichment methods to increase the concentration and quantity of HSPC within the PBMC population. By applying specific enrichment techniques (such as antibody-based magnetic sorting or flow cytometry sorting), the method transforms a low-concentration HSPC population in peripheral blood into a highly enriched population suitable for downstream applications.
Solution Approach 2:
The method combines multiple cell types and enrichment strategies to create a composite approach. It integrates peripheral blood collection, PBMC isolation, and HSPC enrichment within a unified workflow, combining the advantages of easy blood collection with the benefits of targeted stem cell enrichment.
3Reliability
If bone marrow aspiration and biopsy are used, then the reliability of HSPC acquisition is improved, but the time and cost required worsen
Solution Approach 1:
The patent extracts the essential function of obtaining HSPC from the complex bone marrow procedure by isolating and enriching HSPC from peripheral blood. This extraction approach captures the desired outcome (HSPC acquisition) while eliminating the time-consuming and complex bone marrow aspiration and biopsy steps.
Solution Approach 2:
The method creates a copy of the bone marrow HSPC population by enriching for HSPC from peripheral blood. Since HSPC circulate in peripheral blood at low frequencies, the enrichment process creates a representative copy of the bone marrow stem cell population that can be used for the same diagnostic and therapeutic purposes without requiring actual bone marrow access.
4Loss of information
If comprehensive molecular characterization is performed on enriched rare circulating cells, then the diagnostic information obtained is improved, but the complexity of the analysis process worsens
Solution Approach 1:
The patent segments the molecular characterization process into distinct analytical layers: transcriptomic analysis (gene expression), genetic analysis (DNA variants), epigenomic analysis (chromatin accessibility, DNA methylation), and protein expression analysis. Each layer provides specific diagnostic information, and the segmented approach allows for targeted analysis based on the clinical question rather than requiring all analyses simultaneously.
Solution Approach 2:
The enriched HSPC population serves multiple diagnostic and research functions simultaneously. The same enriched cell population can be used for transcriptomic profiling, genetic sequencing, epigenomic characterization, and functional assays, making the enrichment process a universal starting point for comprehensive molecular characterization across multiple analytical platforms.
Data Source
AI summary
The present disclosure encompasses systems, methods, and compositions for enriching a population of rare circulating cells, including progenitor cells, from peripheral blood. Specific embodiments encompass methods of analyzing rare circulating cell transcriptomic, genetic, protein expression, metabolic, epigenomic, and/or other functional assay data to identify differential gene or protein expression and/or chromatin accessibility, and/or functional characteristics. Particular methods relate to enriching and analyzing rare circulating cells in patients following COVID-19 infection, and treating the patient based on the analysis. Embodiments also relate to an enriched population of rare circulating cells from peripheral blood and uses thereof.