Abstract

Blood contains a diverse cell population of low concentration hematopoietic as well as non-hematopoietic cells. The majority of such rare cells may be bone marrow-derived progenitor and stem cells. This paucity of circulating rare cells, in particular in the peripheral circulation, has led many to believe that bone marrow as well as other organ-related cell egress into the circulation is a response to pathological conditions. Little is known about this, though an increasing body of literature can be found suggesting commonness of certain rare cell types in the peripheral blood under physiological conditions. Thus, the isolation and detection of circulating rare cells appears to be merely a technological problem. Knowledge about rare cell types that may circulate the blood stream will help to advance the field of cell-based liquid biopsy by supporting inter-platform comparability, making use of biological correct cutoffs and “mining” new biomarkers and combinations thereof in clinical diagnosis and therapy. Therefore, this review intends to lay ground for a comprehensive analysis of the peripheral blood rare cell population given the necessity to target a broader range of cell types for improved biomarker performance in cell-based liquid biopsy.

Highlights

  • A new window has opened into the diagnostic and theranostic exploitation of blood circulating rare cells (CRC) [1,2]

  • Isolation included the selection of low-density mononuclear cell (MNC) fractions that were obtained by density gradient centrifugation methods

  • An association was found between BCR-ABL transcripts in CML bone marrow cells and likewise high BCR-ABL expression and high nucleated red blood cells (NRBC) counts in the peripheral blood

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Summary

Introduction

A new window has opened into the diagnostic and theranostic exploitation of blood circulating rare cells (CRC) [1,2]. It has been asserted that health and disease are directly associated with the physiology of rare cell populations foremost in bone marrow and tissue and most certainly in the blood [13]. With respect and in realization of the idea of a CRCP, this review intends to comprehend for the first time the possible composition of CRCP in the peripheral blood under physiologic conditions. We intend to identify the “true” biological concentration range in healthy individuals and thirdly, to assess clinical usefulness of each CRC type or in combination with respect to cbLB. This knowledge would largely facilitate the interpretation of cell function for research as well as biomarker translation for early stage diseases. This review shall support our efforts and those of others in CRC biomarker translation, potentially opening up new diagnostic and therapeutic possibilities in cbLB

Megakaryocyte General Background
Circulating
Megakaryocyte Isolation
MKC Clinical Usefulness
Endothelial Cell General Background
Circulating Endothelial Cells
Endothelial Cell Isolation
Collection
Endothelial Cell Clinical Use
Erythroblast General Background
Circulating Erythroblasts
Fibroblast-like Cells
Fibrocyte General Background
Mesenchymal Stem Cells General Background
Circulating Fibroblast-Like Cells Clinical Usefulness
Very Small Embryonic Stem Cell General Background
VSEL Stem Cell Clinical Usefulness
Epithelial Cell General Background
Circulating Epithelial Cells
Circulating EC Usefulness
Miscellaneous
Circulating Rare Cell Population Concentrations
Findings
10. Concluding Remarks
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