Exhaustion of nucleus pulposus progenitor cells with ageing and degeneration of the intervertebral disc.

Despite the high prevalence of intervertebral disc disease, little is known about changes in intervertebral disc cells and their regenerative potential with ageing and intervertebral disc degeneration. Here we identify populations of progenitor cells that are Tie2 positive (Tie2+) and disialoganglioside 2 positive (GD2+), in the nucleus pulposus from mice and humans. These cells form spheroid colonies that express type II collagen and aggrecan. They are clonally multipotent and differentiated into mesenchymal lineages and induced reorganization of nucleus pulposus tissue when transplanted into non-obese diabetic/severe combined immunodeficient mice. The frequency of Tie2+ cells in tissues from patients decreases markedly with age and degeneration of the intervertebral disc, suggesting exhaustion of their capacity for regeneration. However, progenitor cells (Tie2+GD2+) can be induced from their precursor cells (Tie2+GD2-) under simple culture conditions. Moreover, angiopoietin-1, a ligand of Tie2, is crucial for the survival of nucleus pulposus cells. Our results offer insights for regenerative therapy and a new diagnostic standard

Extracellular mRNA transported to the nucleus exerts translation-independent function

Nonvesicular extracellular RNA (nex-RNA) that are not packed in extracellular vesicles is detected outside the cell, but it is poorly understood. Here the authors report that nex-RNA is captured by a zinc finger protein and transported to the nucleus to enhance antimetastatic characters of the cell

Hepato‐entrained B220+CD11c+NK1.1+ cells regulate pre‐metastatic niche formation in the lung

Abstract Primary tumours establish metastases by interfering with distinct organs. In pre‐metastatic organs, a tumour‐friendly microenvironment supports metastatic cells and is prepared by many factors including tissue resident cells, bone marrow‐derived cells and abundant fibrinogen depositions. However, other components are unclear. Here, we show that a third organ, originally regarded as a bystander, plays an important role in metastasis by directly affecting the pre‐metastatic soil. In our model system, the liver participated in lung metastasis as a leucocyte supplier. These liver‐derived leucocytes displayed liver‐like characteristics and, thus, were designated hepato‐entrained leucocytes (HepELs). HepELs had high expression levels of coagulation factor X (FX) and vitronectin (Vtn) and relocated to fibrinogen‐rich hyperpermeable regions in pre‐metastatic lungs; the cells then switched their expression from Vtn to thrombospondin, both of which were fibrinogen‐binding proteins. Cell surface marker analysis revealed that HepELs contained B220+CD11c+NK1.1+ cells. In addition, an injection of B220+CD11c+NK1.1+ cells successfully eliminated fibrinogen depositions in pre‐metastatic lungs via FX. Moreover, B220+CD11c+NK1.1+ cells demonstrated anti‐metastatic tumour ability with IFNγ induction. These findings indicate that liver‐primed B220+CD11c+NK1.1+ cells suppress lung metastasis