Monday, December 8, 2008

Understanding of bone marrow SC niche expanded

Detection of functional haematopoietic stem cell niche using real-time imaging by Yucai Xie, Tong Yin, Winfried Wiegraebe and 15 co-authors, including Ricardo A Feldman and Linheng Li, Nature 2008(Dec 3) [Epub ahead of print]. PubMed Abstract:
Haematopoietic stem cell (HSC) niches, although proposed decades ago, have only recently been identified as separate osteoblastic and vascular microenvironments. Their interrelationships and interactions with HSCs in vivo remain largely unknown. Here we report the use of a newly developed ex vivo real-time imaging technology and immunoassaying to trace the homing of purified green-fluorescent-protein-expressing (GFP(+)) HSCs. We found that transplanted HSCs tended to home to the endosteum (an inner bone surface) in irradiated mice, but were randomly distributed and unstable in non-irradiated mice. Moreover, GFP(+) HSCs were more frequently detected in the trabecular bone area compared with compact bone area, and this was validated by live imaging bioluminescence driven by the stem-cell-leukaemia (Scl) promoter-enhancer. HSCs home to bone marrow through the vascular system. We found that the endosteum is well vascularized and that vasculature is frequently localized near N-cadherin(+) pre-osteoblastic cells, a known niche component. By monitoring individual HSC behaviour using real-time imaging, we found that a portion of the homed HSCs underwent active division in the irradiated mice, coinciding with their expansion as measured by flow assay. Thus, in contrast to central marrow, the endosteum formed a special zone, which normally maintains HSCs but promotes their expansion in response to bone marrow damage.
Found via: Understanding Of Bone Marrow Stem Cell Niche Expanded, Health News. Excerpt:
“EVISC technology will allow us to study HSC lineage commitment in vivo,” said Linheng Li, Ph.D., Investigator and senior author on the paper. “Furthermore, we will be able to use this technology to study leukemia (and other cancer) stem cells to better understand whether they use the same or different niches that normal stem cells use, and even to evaluate drug resistance and treatment responses. This is an exciting new avenue for our work.”

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