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Nonmarrow Hematopoiesis Occurs in a Hyaluronic-Acid-Rich Node and Duct System in Mice
Hwang, Sunhee,Lee, Seung J.,Park, Sang H.,Chitteti, Brahmananda R.,Srour, Edward F.,Cooper, Scott,Hangoc, Giao,Broxmeyer, Hal E.,Kwon, Byoung S. Mary Ann Liebert 2014 STEM CELLS AND DEVELOPMENT Vol.23 No.21
<P>A hyaluronic-acid-rich node and duct system (HAR-NDS) was found on the surface of internal organs of mice, and inside their blood and lymph vessels. The nodes (HAR-Ns) were filled with immune cells of the innate system and were especially enriched with mast cells and histiocytes. They also contained hematopoietic progenitor cells (HPCs), such as granulocyte-macrophage, erythroid, multipotential progenitors, and mast cell progenitors (MCPs). MCPs were the most abundant among the HPCs in HAR-Ns. Their frequency was fivefold higher than that of the MCPs in bone marrow. In addition, the system contained pluripotent stem cells (PSCs) capable of producing CD45(-)Flk1(+) hemangioblast-like cells, which subsequently generated various types of HPCs and differentiated blood cells. Although HAR-Ns did not appear to harbor enough number of cells capable of long-term reconstitution or short-term radioprotection of lethally irradiated recipients, bone marrow cells were able to engraft in the HAR-NDS and reconstitute hematopoietic potentials of the system. PSCs and HPCs were consistently found in intravenous, intralymphatic, and intestinal HAR-ND. We infer that PSCs and HPCs reside in the HAR-ND and that this novel system may serve as an alternative means to traffic immature and mature blood cells throughout the body.</P>
Enhancing Hematopoietic Stem Cell Transplantation Efficacy by Mitigating Oxygen Shock
Mantel, Charlie R.,O'Leary, Heather A.,Chitteti, Brahmananda R.,Huang, X.,Cooper, S.,Hangoc, G.,Brustovetsky, N.,Srour, Edward F.,Lee, M.,Messina-Graham, S.,Haas, David M.,Falah, N.,Kapur, R.,Pelus, L Cell Press ; MIT Press 2015 Cell Vol.161 No.7
Hematopoietic stem cells (HSCs) reside in hypoxic niches within bone marrow and cord blood. Yet, essentially all HSC studies have been performed with cells isolated and processed in non-physiologic ambient air. By collecting and manipulating bone marrow and cord blood in native conditions of hypoxia, we demonstrate that brief exposure to ambient oxygen decreases recovery of long-term repopulating HSCs and increases progenitor cells, a phenomenon we term extraphysiologic oxygen shock/stress (EPHOSS). Thus, true numbers of HSCs in the bone marrow and cord blood are routinely underestimated. We linked ROS production and induction of the mitochondrial permeability transition pore (MPTP) via cyclophilin D and p53 as mechanisms of EPHOSS. The MPTP inhibitor cyclosporin A protects mouse bone marrow and human cord blood HSCs from EPHOSS during collection in air, resulting in increased recovery of transplantable HSCs. Mitigating EPHOSS during cell collection and processing by pharmacological means may be clinically advantageous for transplantation.