Stem cells on patrol

Abstract

Hematopoietic stem cells (HSCs) exist in the bone marrow and circulate in the blood. In this issue, Massberg et al. (2007) report that HSCs also travel through the lymphatic system. Furthermore, migration of HSCs--which express Toll-like receptors--allows the recognition of pathogenic molecules in peripheral tissues thereby promoting the local generation of innate immune cells at the site of infection.

Figure 1. Migration of hematopoietic stem and progenitor cells

(1) Many stem cells reside in association with osteoblasts in trabecular bone. (2) An even greater number are close to centrally located vascular sinuses, but little is known about exchange between these two locations. (3) Pathogen products and cytokines released during infection can mobilize hematopoietic stem and progenitor cells (HSPCs), which migrate out of the marrow into blood, but small numbers exit under normal circumstances. HSPCs remain in the circulation for only seconds but reside in tissues such as the lungs, liver and spleen for at least 36 hours. (4) Their stay is extended by recognition of microbial or viral products by the Toll-like receptors (TLR) that they express. Dendritic and myeloid cells are produced locally from HSPCs in response to particular TLR ligands, and these effectors of the innate immune system presumably fight infections and promote tissue repair. (5) Unstimulated HSPCs use their sphingosine-1-phosphate receptors (such as S1P₁) to recognize steep gradients of sphingosine -1-phosphate and to enter the lymph (green). (6) HSPCs quickly transit through one or more lymph nodes before returning to the blood via the thoracic duct. (7) At least some stem cells return to marrow niches, but it is not known if they are affected by the journey.