An update of circulating rare cell types in healthy adult peripheral blood: findings of immature erythroid precursors

Abstract

Background: Circulating rare cells (CRCs) are benign or malignant minuscule events in the peripheral blood or other bodily fluids. The detection and quantification of certain CRC types is an invaluable or proposed candidate biomarker for diagnosis, prognosis and prediction of various pathological conditions. The list of CRC types and biomarker applicability thereof continues to expand along with improvements in cell selection technology. Past findings may suggest commonness of healthy donor peripheral blood circulating mature erythroblasts. This work suggests the occurrence of morphologically distinct bone marrow native circulating early erythroid precursors that we intend to add to the list of CRCs. Methods: We tested 15 healthy individuals that varied in age and gender employing a negative cell selection assay based on magnetic bead technology to characterize healthy adult circulating CD45 negative cell events using cell surface markers CD71 and glycophorin-A. Results: Positive events were detected and varied in cell and nuclear size ranging between 7.5 µm till 15 µm and 4.5 till 9.2 µm, respectively with distinct appearance under bright field microscope. Cell rarity increased with cell and nuclear size. Largest cells exceeded 13.5 µm in cell diameter and were found in 7 out of 15 donors. Conclusions: Circulating erythroid precursors occur at different stages of maturation and may be part of the benign CRC spectrum.

The Blood Circulating Rare Cell Population. What Is It and What Is It Good for?

“…Nevertheless, NRBC are commonly present in the peripheral blood even in healthy individuals. Prove has been provided consistently throughout the decades by non-invasive pre-natal testing (NIPT) [114,115] and recent investigations on rare cells in peripheral blood [2,10] Most explanations for the presence of NRBC in the peripheral blood relate to impaired erythropoiesis that has been divided into three categories; inefficient erythropoiesis for example caused by thalassemia, stress induced erythropoiesis for example erythropoietic resumption after chemotherapy, and pathological erythropoiesis due to primary abnormalities in hematopoiesis (for example caused by various leukemias). In general pathological erythropoietic activity is considered a consequence of hypoxic stress [113,116].…”

“…Given the abundance in findings even though at low concentrations, a regular or physiological traffic between circulation and bone marrow can be expected. Unusual may be the finding of NRBC at different maturation stages suggesting a non-accidental [10]. In fact, immune activity has been postulated as well as the ability of EB to actively leave the bone marrow [117].…”

“…Kwon et al [119] compared density gradient modalities and concluded that high EB yield can be achieved by optimized osmolarity and double-density gradient system. Negative selection magnetic particle technology was proposed for efficient EB detection [2,10,120]. More recently, Schreier et al [10].…”

“…Negative selection magnetic particle technology was proposed for efficient EB detection [2,10,120]. More recently, Schreier et al [10]. relied on RBC lysis followed by macroscale automated rare cell enrichment and [2] employed the CTC-iCHIP platform, a microchip that firstly removes RBC and then separates magnetic from non-magnetic material.…”

“…Therefore, the potentials of cbLB extend beyond their current boundaries. Consequently, in view of accidental findings and occasional investigations on CRC other than cancer-associated cell types, the CRC concept needs further adaption and comprehension [2,10,11].…”