By Christine Duncan, MD, and Tobias Neff, MD
Stem cells continue to be all the rage — just ask any bone
marrow transplant specialist. Much has been learned in recent years about the
physiology of embryonic and adult stem cells. In yesterday’s much anticipated
Plenary Session, we witnessed the convergence of many recent important findings
that in isolation have moved the stem cell research field ahead substantially:
Hematopoietic stem cells (HSCs) depend on endosteal niches and can be
manipulated via parathyroid hormone (PTH) (Calvi et al. 2003; Nature.
425:841-6); HSCs are found in perivascular niches (Kiel et al. 2005; Cell. 121:1109-21); HSC
mobilization is regulated via signals mediated by adrenergic innervations (Katayama et al. 2006; Cell. 124:407-21); and
bone marrow contains multipotential stem and progenitor cells (Jiang et al.
2002; Nature. 418:41-49).
Méndez-Ferrer from Mount Sinai School of Medicine presented data that
characterize the elusive mesenchymal stem cell (MSC) in more detail. Dr.
Méndez-Ferrer and his colleagues prospectively isolated this rare population of
bone marrow cells by selecting for the expression of nestin, hitherto known as
a marker of neural stem cells and hair follicle stem cells, and selecting
against the expression of the endothelial marker CD31 and the panhematopoietic
marker CD45. The investigators demonstrated for the first time in vivo
self-renewal and multilineage differentiation of MSCs and provided evidence
that this cell is a critical component for the formation of the HSC niche. The
studies included transplantation experiments that demonstrated the recruitment
of bona fide HSCs to MSCs and genetic ablation experiments that demonstrated
dependence of the niche and of HSCs in vivo on MSCs. Furthermore,
manipulation of MSC physiology via sympathetic innervation, PTH, and G-CSF
resulted in alterations in the cell cycle or in the differentiation of these
cells. This is an intriguing observation, as all three interventions have been
implicated in changing HSC behavior.
These exciting results point the way toward a resolution
of a number of previously unanswered questions in the field. For example, what is the nature of the
signals that maintain “stemness” in the HSC pool? How does stem cell
mobilization work? Do HSCs and MSCs reciprocally signal to each other?
The clinical and basic discovery potential for MSCs is
substantial. MSCs have already entered the clinic for regenerative purposes and
for the treatment of GVHD. The data described yesterday provide an additional
boost to this exciting area of investigation.
Drs. Duncan and Neff indicated no relevant conflicts
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