Such terms as “osteoblasts” and “endosteal region” have been commonly used in scientific literature to describe the bone marrow niche for hematopoietic stem cells (HSC). However, a recent review by Maria Askmyr warns that using these terms could mislead us in attempts to describe the true nature of the HSC nice.
… the term ‘osteoblastic niche’ is oversimplified and potentially incorrect in regard to which cells actively regulate HSC maintenance and self-renewal. Researchers have used the generic term ‘osteoblasts’ to refer to a spectrum of cell types of the osteoblastic lineage. However, osteoblasts are a well-defined population of differentiated cells actively involved in bone formation. The terminology ‘endosteal niche’ is also misrepresentative because the endosteal surface of bone includes all cells that line the interface between bone and marrow, including both endocortical (i.e. inner cortical) and trabecular surfaces.
The review highlight that some cell types withing osteoblastic lineage in the bone marrow actively regulate HSC maintenance, but some are more likely not.
There is some evidence that HSC can function without support of osteoblastic lineage cells. For example – embryonic hematopoiesis, extramedullar hematopoiesis in bone marrow ablation conditions or some hematological diseases, long-term hematopoietic cell culture on stromal feeder. Also, if we look at all studies that describe extrinsic factors regulating HSC in bone marrow (osteopontin, angiopoetins, SCF, SDF-1, TPO, Jagged, calcium, N-cadherin…), we can see lack of evidence for their exclusive expression by a particular cell type.
Precursors of the osteoblast lineage, such as pre-osteoblasts and SSCs (Skeletal Stem Cells), express molecules shown to be important for HSC regulation (such as CXCL12, Ang-1 and SCF) and might play an active part in the HSC niche. Indeed, stromal cells that support hematopoiesis are reminiscent of immature osteoblasts and are grown in culture conditions in which spontaneous mature osteoblast cell differentiation does not normally occur. In contrast, mature cells of the osteoblast lineage (including osteoblasts, bone lining cells and osteocytes) are unlikely to be active participants in the HSC-supportive niche.
It seems to me that HSC maintenance, together with intrinsic, regulated by extrinsic factors (niche microenvironment), produced by different cell types. Conditional knockout mice models for particular cell type withing osteoblastic lineage can resolve the controversy surrounding the true nature of the HSC niche.
Nice review. Highly recommended.
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