Abstract

Stem cells are nurtured and regulated by a specialized microenvironment known as stem cell niche. While the functions of the niches are well defined, their structure and location remain unclear. We have identified, in rat bone marrow, the seat of hematopoietic stem cells—extensively vascularized node-like compartments that fit the requirements for stem cell niche and that we called hemmules. Hemmules are round or oval structures of about one millimeter in diameter that are surrounded by a fine capsule, have afferent and efferent vessels, are filled with the extracellular matrix and mesenchymal, hematopoietic, endothelial stem cells, and contain cells of the megakaryocyte family, which are known for homeostatic quiescence and contribution to the bone marrow environment. We propose that hemmules are the long sought hematopoietic stem cell niches and that they are prototypical of stem cell niches in other organs.

Highlights

  • The bone marrow stem cells are very sensitive to their immediate environment [1]

  • We will demonstrate that hemmule structural and cellular properties are very distinct from those of the control samples of bone marrow, lymph node, and blood vessel, and we will examine whether or not the hemmule properties meet the Schofield criteria of a stem cell niche [22]: (1) a distinct anatomic position, (2) a space where stem cells can be maintained and replicate, (3) a place where differentiation was inhibited, and (4) a restricted space that limited the quantities of stem cells

  • While replicating the Blazsek hematon procedure [11], we noticed that peculiar nodes can be extracted from the split bone without aspiration of bone marrow

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Summary

Introduction

The bone marrow stem cells are very sensitive to their immediate environment [1]. it is important to nurture these cells in a specialized environment known as the stem cell niche [2,3,4]. Blazsek and colleagues described a structure later termed hematon [8,9] that was proposed as the primary fundamental unit of hematopoiesis. The hematon is a spheroid (node) that measures around 100–500 micrometers in diameter. The procedure of hematon separation from the adult mouse femoral bone includes mechanical fractionation of bone marrow that involves dilacerations by scalpels and the removal of hematons by aspiration [11]. This procedure makes it difficult to determine the original location of hematons and their potential interconnections, questioning whether the hematon is a stem cell niche

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