Understanding Of Bone Marrow Stem Cell Niche Expanded

The Linheng Li Lab collaborated with several of the Institute’s support facilities to develop a new technology — ex vivo Imaging of Stem Cells, or EVISC — to monitor the dynamic behavior of stem cells. This technology enabled the team to track the homing of hematopoietic stem cells after being transplanted in mice. The findings build on the Linheng Li Lab’s 2003 discovery of the hematopoietic stem cell (HSC) niche (Zhang, et al. in the October 23, 2003 issue of Nature).

“Using the EVISC technology, we were able to confirm our 2003 findings that HSCs tend to home to the inner bone surface,” said Yucai Xie, Predoctoral Researcher and co-equal first author on the paper. “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.”

Tong Yin, Ph.D., Postdoctoral Research Fellow, is also a co-equal first author on the paper.

A better understanding of the HSC niche may lead to more effective bone marrow transplants since a more precise understanding of the microenvironment that nurtures these therapeutically valuable cells will give physicians greater control over the entire process.

“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,” said Winfried Wiegraebe, Ph.D., Director of Advanced Instrumentation and Physics, who provided the key assistance in the two-photon microscopic experiments.

“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.”

Additional contributing authors from the Stowers Institute include Xi He, M.D., Senior Research Specialist; Danny Stark, Research Technician III; Katherine Perko, Research Technician I; Richard Alexander, Senior Research Technician; Joel Schwartz, Ph.D., Managing Director of Imaging Center; Justin Grindley, Ph.D., Senior Research Associate; Jungeun Park, Research Technician II; Jeff Haug, Managing Director - Cytometry Facility; Joshua Wunderlich, Research Technician; Hua Li, Ph.D., Biostatistician; Simon Zhang, Laboratory Assistant; Teri Johnson, Managing Director - Histology Facility; University of Maryland School of Medicine.

Contributing authors from the University of Maryland School of Medicine include Diana Miller and Ricardo Feldman, Ph.D.