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New Study Sheds Light on the Mysteries of the Bone Marrow Stem Cell Niche

Nature, December 5, 2008

Scientists have finally determined the answer to a question that has been on the minds of most stem cell scientists for years: namely, where, exactly, in precise anatomical terms, are bone marrow stem cells produced? Thanks to the invention of new imaging technology, this mystery has now been solved.

In collaboration with several of the support facilities at the Stowers Institute in Kansas City, Missouri, the Linheng Li Lab led the development of the new "ex vivo imaging of stem cells" (EVISC) technology, which monitors in real time the dynamic behavior of stem cells. Using the EVISC, scientists were finally able to observe and track the homing of hematopoietic stem cells after transplantation in mice, which led to the discovery of the newly identified bone marrow niche. This is not the first time that the Linheng Li Lab has pioneered such breakthroughs, as the Lab was already renowned for its discovery in 2003 of the hematopoietic stem cell (HSC) niche, which was reported by Zhang et al. in Nature.

Now, according to Dr. Yucai Xie, predoctoral researcher and a coauthor of the most recent paper, "Using the EVISC technology, we were able to confirm our 2003 findings that HSCs tend to home to the inner bone surface. Additionally, we were able to resolve a debate in the field about whether the bone-forming niche or the blood-vessel-forming niche actually nurtures HSCs. Surprisingly, we revealed that the inner bone surface forms a special zone that includes both osteoblastic and endothelial components. This HSC zone maintains HSCs in their resting state and promotes HSC expansion in response to bone marrow stressors, such as irradiation."

Scientists have long wondered about the precise location of the HSC niche, as well as details about the nature of the microenvironment of this niche, a better understanding of which would assist with the development of more effective bone marrow transplants by giving scientists and physicians greater control over the entire process by which stem cells from bone marrow are harvested and expanded. According to Dr. Winfried Wiegraebe, director of the Stowers Institute's Advanced Instrumentation and Physics division, who assisted with the famed two-photon experiments, "The new technique developed in this study may have a variety of applications including monitoring other types of cells in low population numbers in vivo." As Dr. Linheng Li adds, "EVISC technology will allow us to study HSC lineage commitment in vivo. 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."

Additional study and experimentation are now planned that will further examine the characteristics and processes that are unique to this niche. The mere fact that the inner bone surface actually forms a separate, distinct, unique zone with both osteoblastic and endothelial components, in which HSCs are maintained in their resting state and expanded in response to bone marrow stressors, is in and of itself a discovery with far-reaching applications to the field of regenerative medicine.



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