Functional Isolation of the Low-oxygenic Niche Derived Primitive Hematopoietic Stem Cells By Differential ROS Activity

Abstract (Set) A low-oxygenic niche in bone marrow limits reactive oxygen species (ROS) production, thus providing long-term protection for hematopoietic stem cells (HSCs) from ROS stress. Although many approaches have been used to enrich HSCs, none have been designed to isolate primitive HSCs located within the low-oxygenic osteoblastic-niche due to difficulties of direct physical access. Scientists at JHU show that an early HSC population that might reside in the osteoblastic niche can be functionally isolated by taking advantage of the relative intracellular ROS activity. Primitive HSCs in the low-oxygenic osteoblastic niche, the ROS low population, exhibit attributes such as quiescence, and higher levels of calcium receptor, N-cadherin, Notch1, and p21. The ROS1ow population also has a higher self-renewal potential than HSC populations derived from greater oxygenic environments. More potent and primitive HSCs associated with the low-oxygenic niche can be indirectly isolated by selecting for the low-level of ROS expression. The ROS related signaling pathways, together with specific characteristics of niche-HSCs, may serve as targets for beneficial therapies. Description (Set) Proposed Use (Set) This invention is the first approach for purifying the low-oxygenic niche derived hematopoietic stem cells which are the most potent HSCs. When compared to the current HSC isolation methods such as cell surface phenotype selection, this novel invention functionally selects for the low-oxygenic niche specific HSC population. The methods described in this invention for isolating ROSlow hematopoietic stem cells may be adapted into commercial stem cell isolation kits to be sold by the laboratory reagents market. It is also envisioned that the functionally selected niche HSC subsets may be marketed as tangible property and could aid in the discovery of potential targets for therapies for human diseases, especially hematologic malignancies.

Inventor(s): Jang, Yoon-Young ,Sharkis, Saul

Type of Offer: Licensing

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