Concise Review: Paracrine Functions of Vascular Niche Cells in Regulating Hematopoietic Stem Cell Fate

Abstract

The functions of endothelial cells (ECs) in regulating oxygen delivery, nutrient exchange, coagulation, and transit of inflammatory cells throughout the body are well--established. ECs have also been shown to regulate the maintenance and regeneration of organ-specific stem cells in mammals. In the hematopoietic system, hematopoietic stem cells (HSCs) are dependent on signals from the bone marrow (BM) vascular niche for their maintenance and regeneration after myelosuppressive injury. Recent studies have demonstrated the essential functions of BM ECs and perivascular stromal cells in regulating these processes. In the present study, we summarize the current understanding of the role of BM ECs and perivascular cells in regulating HSC maintenance and regeneration and highlight the contribution of newly discovered EC-derived paracrine factors that regulate HSC fate. Stem Cells Translational Medicine 2017;6:482-489.

Keywords: Bone marrow stromal cells; Endothelial cell; Hematopoietic stem cells; Microenvironment; Self-renewal.

Figure 1

Paracrine factors in the bone marrow (BM) vascular niche. A schematic diagram of a BM vessel in longitudinal view and representation of several paracrine factors that are secreted by BM endothelial cells and perivascular cells. Abbreviations: CXCL12, C‐X‐C chemokine ligand 12; CXCR4, C‐X‐C chemokine receptor type 4; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; HSC, hematopoietic stem cell; Jag1, Jagged‐1; Jag2, Jagged‐2; PTN, pleiotrophin; PTP‐ζ, protein receptor tyrosine phosphatase‐ζ; SCF, stem cell factor.