Hematopoietic stem cell niche maintenance during homeostasis and regeneration

Abstract

The bone marrow niche has mystified scientists for many years, leading to widespread investigation to shed light into its molecular and cellular composition. Considerable efforts have been devoted toward uncovering the regulatory mechanisms of hematopoietic stem cell (HSC) niche maintenance. Recent advances in imaging and genetic manipulation of mouse models have allowed the identification of distinct vascular niches that have been shown to orchestrate the balance between quiescence, proliferation and regeneration of the bone marrow after injury. Here we highlight the recently discovered intrinsic mechanisms, microenvironmental interactions and communication with surrounding cells involved in HSC regulation, during homeostasis and in regeneration after injury and discuss their implications for regenerative therapy.

Osteopontin attenuates aging‐associated phenotypes of hematopoietic stem cells

“…Cells that are located < 10 cell diameters to the bone are enriched for stroma cells from the endosteal region of the bone referred to as the endosteal niche and were detached for our experiments by collagenase treatment (Fig 2Ai–iii). This cell population is thus enriched in non‐hematopoietic stroma cells and, as most of the vascular structures are present in this region, contains all types of stroma cells present in the BM (Mendelson & Frenette, 2014). Flow cytometric analyses identified a decrease in the frequency of stroma cells (CD45 − Ter119 − , Fig EV1A) as well as osteoblasts (OBs, CD45 − Ter119 − CD31 − Sca1 − CD51 + cells) upon aging, while the frequency of other niche cell populations like CD31 + endothelial cells (gated as CD45 − Ter119 − Sca1 + CD31 + ), mesenchymal stem cells (MSCs gated as CD45 − Ter119 − CD31 − Sca1 + CD51 + ) and CXCL12 abundant reticular cells (CAR + cells gated as CD45 − Ter119 − CD31 − CXCL12 + ) was similar (Fig 2B).…”

Communication of bone cells with hematopoiesis, immunity and energy metabolism

“…[26][27][28] Most of them are mesenchymal lineage cells, and, among them, nestin þ mesenchymal stem cells and CXCL12-abundant reticular cells (CAR cells) are proven to possess differentiation capacity into osteoblasts. 29,30 From the bone researcher's point of view, the structure of the BM as the hematopoietic microenvironment may be simplified as illustrated in Figure 1.…”

Ex vivo expansion of hematopoietic stem cells

“…In 1978, the concept of HSC niche was introduced by Schofield [26]. Since then, mounting evidence indicates that the niche plays a crucial role in quiescence, self-renewal, differentiation, apoptosis, migration, and immune privilege of HSCs [27][28][29]. Several types of cells that potentially form bone marrow HSC niches have been reported [27][28][29][30].…”