Nestin expression in osteocytes following myeloablation and during bone marrow metastasis

Abstract

Nestin, originally described in neuroepithelial stem cells, 1 is an intermediate filament expressed during early stages of development. Its expression inversely correlates with cellular differentiation. In the bone marrow (BM), nestin is expressed in perivascular mesenchymal stem cells (MSCs) which contribute to bone development and are in direct contact with haematopoietic stem cells (HSCs). MSCs are multipotent cells capable of differentiating into osteoblastic, chondrocytic and adipocytic cells. Their presence in the BM was first described by Caplan. 2 Subsequently, nestin was broadly used as an MSC and HSC marker in the BM with little attention as to its expression pattern in mature osteocytes. Notably, researchers found distinct nestin + MSCs distributed around blood vessels. 3 Based on cell fluorescence intensity and cellular morphology in nestin fluorescent protein fusion protein tagged (Nes-GFP) transgenic mice, two distinct types of Nes-GFP+ mesenchymal progenitor cell types (Nes-GFPbright and Nes-GFPdim) were identified. Nes-GFPbright cells contained most CFU-Fs and a higher expression of genes which are associated with the HSC niche. By contrast, DNA replication and cell cycle pathways were significantly enriched in

Neuropilin2 in Mesenchymal Stromal Cells as a Potential Novel Therapeutic Target in Myelofibrosis

“…Myelofibrosis grading was performed according to the WHO criteria for MPN [20]. NRP2 immunohistochemistry (IHC) on standard paraffin sections (2-3 µm) was performed manually as previously described with the addition of avidin/biotin blocking as described by the manufacturer (Avidin/Biotin Blocking Kit, Vector Laboratories, Burlingham, CA, USA) [21]. For other staining, epitope retrieval was performed at pH6 (Medak PMB-1-250; 20 min at 99 • C) and sections were developed using DAB IHC detection system on a semi-automatic immunohistochemistry stainer (Autostainer 480S; Medac, Wedel, Germany) [22].…”