Is CD34 truly a negative marker for mesenchymal stromal cells?

Abstract

The prevailing school of thought contents that mesenchymal stem cells (MSCs) do not express CD34, and this sets MSCs apart from hematopoietic stem cells (HSCs), which express CD34. However, the evidence for MSCs being CD34- is largely based on cultured MSCs, not tissue-resident MSCs, and the existence of CD34- HSCs is in fact well documented. Furthermore, the Stro-1 antibody, which has been extensively used for the identification/isolation of MSCs, was generated by using CD34+ bone marrow cells as immunogen. Thus, neither MSCs being CD34- nor HSCs being CD34+ is entirely correct. In particular, two studies that analyzed CD34 expression in uncultured human bone marrow nucleated cells both found that MSCs (BMSCs) existed in the CD34+ fraction. Several studies also found that freshly isolated adipose-derived MSCs (ADSCs) expressed CD34. In addition, all of these ADSC studies and several other MSC studies observed disappearance of CD34 expression when the cells were propagated in culture. Thus, available evidence points to CD34 being expressed in tissue-resident MSCs, and its negative finding being a consequence of cell culturing.

CD34-negative mesenchymal stem-like cells may act as the cellular origin of human aortic valve calcification

“…These MSLCs comprised both CD34-positive and -negative cells, despite being CD45-negative. [20]. In this study, we confirmed that calcification of CD34-negative MSLCs was rapidly induced using high inorganic phosphate (3.2 mM).…”

The Human Mesenchymal Stem Cells and the Chick Embryo Chorioallantoic Membrane: The Key and the Lock in Revealing Vasculogenesis

“…Lin et al suggest that available evidence points to CD34 being expressed in tissue-resident MSC and its negative finding being a consequence of cell culturing. In addition, CD34 expression in vivo 31: 1139-1144 (2017) correlates with enhanced vasculogenic and angiogenic potential, but also with replicative capacity and stemness, while loss of CD34 expression might be related to lineage commitment (15). In our study, we evaluated the CD34 expression using two antibodies, one for chicken/human CD34 (cCD34) and another one for human CD34 (hCD34).…”

Podoplanin discriminates distinct stromal cell populations and a novel progenitor subset in the liver

“…CD34, a hematopoetic stem cell marker, has also been identified in bone marrowmesenchymal stem cells and adipose tissue-derived stem cells (20). Importantly, the frequency of this progenitor population showed selective expansion in liver injury associated with Mdr2 deficiency.…”