Wu Wan

Novel insight into stem cell mobilization-plasma sphingosine-1-phosphate is a major chemoattractant that directs the egress of hematopoietic stem progenitor cells from the bone marrow and its level in peripheral blood increases during mobilization due to activation of complement cascade/membrane attack complex.

The complement cascade (CC) becomes activated and its cleavage fragments play a crucial role in the mobilization of hematopoietic stem/progenitor cells (HSPCs). Here, we sought to determine which major chemoattractant present in peripheral blood (PB) is responsible for the egress of HSPCs from the bone marrow (BM). We noticed that normal and mobilized plasma strongly chemoattracts HSPCs in a stromal-derived factor-1 (SDF-1)-independent manner because (i) plasma SDF-1 level does not correlate with mobilization efficiency; (ii) the chemotactic plasma gradient is not affected in the presence of AMD3100 and (iii) it is resistant to denaturation by heat. Surprisingly, the observed loss of plasma chemotactic activity after charcoal stripping suggested the involvement of bioactive lipids and we focused on sphingosine-1-phosphate (S1P), a known chemoattracant of HSPCs. We found that S1P (i) creates in plasma a continuously present gradient for BM-residing HSPCs; (ii) is at physiologically relevant concentrations a chemoattractant several magnitudes stronger than SDF-1 and (iii) its plasma level increases during mobilization due to CC activation and interaction of the membrane attack complex (MAC) with erythrocytes that are a major reservoir of S1P. We conclude and propose a new paradigm that S1P is a crucial chemoattractant for BM-residing HSPCs and that CC through MAC induces the release of S1P from erythrocytes for optimal egress/mobilization of HSPCs.

Hunt for Pluripotent Stem Cell – Regenerative Medicine Search for Almighty Cell

Regenerative medicine and tissue engineering are searching for a novel stem cell based therapeutic strategy that will allow for efficient treatment or even potential replacement of damaged organs. The pluripotent stem cell (PSC), which gives rise to cells from all three germ lineages, seems to be the most ideal candidate for such therapies. PSC could be extracted from developing embryos. However, since this source of stem cells for potential therapeutic purposes remains controversial, stem cell researchers look for PSC that could be isolated from the adult tissues or generated from already differentiated cells. True PSC should possess both potential for multilineage differentiation in vitro and, more importantly, also be able to complement in vivo blastocyst development. This review will summarize current approaches and limitations to isolate PSC from adult tissues or, alternatively, to generate it by nuclear reprogramming from already differentiated somatic cells.

Higher number of stem cells in the bone marrow of circulating low Igf-1 level Laron dwarf mice—novel view on Igf-1, stem cells and aging

Aging-associated changes in the nuclear architecture, chromatin structure, altered expression and activity of chromatin remodeling factors, and the change in pattern of epigenetic marks (DNA methylation and histone modification) affect all cells in the adult body, including the population of stem cells (SCs) that is responsible for proper tissue rejuvenation.1 The elucidation of these precise mechanisms will help to develop more efficient anti-aging strategies as well as facilitate a better understanding of age-related risks for cancer genesis.

A Pivotal Role of Activation of Complement Cascade (CC) in Mobilization of Hematopoietic Stem/Progenitor Cells (HSPC)

Complement cascade (CC) and innate immunity emerge as important and underappreciated modulators of trafficking of hematopoietic stem/progenitor cells (HSPC). Accordingly, we reported that (i) C becomes activated in bone marrow (BM) during G-CSF-induced mobilization by the classical immunoglobulin (Ig)-dependent pathway, and that (ii) C3 cleavage fragments increase the responsiveness of HSPC to an stromal derived factor-1 (SDF-1) gradient. Furthermore, our recent data in immunodeficient mice support the concept that the CC is a major factor modulating egress of HSPC from bone marrow (BM) into peripheral blood (PB). Thus, in light of these findings, mobilization of HSPC could be envisioned as part of an immune response that requires CC activation by the classical Ig-dependent and/or Ig-independent pathways. Hence modulation of CC activation could allow for the development of more efficient mobilization strategies in patients who are poor mobilizers of HSPC.