Sources of Hematopoietic Stem and Progenitor Cells and Methods to Optimize Yields for Clinical Cell Therapy  Sandhya R. Panch, James Szymanski, Bipin N. Savani, David F. Stroncek  Biology of Blood and Marrow Transplantation  Volume 23, Issue 8, Pages 1241-1249 (August 2017) DOI: 10.1016/j.bbmt.2017.05.003 Copyright © 2017 Terms and Conditions

Figure 1 Milestones in HSPC collection and characterization for clinical cellular therapy. FACS indicates fluorescence-activated cell sorting; MABs, monoclonal antibodies; FDA, US Food and Drug Administration; NHL, non-Hodgkin lymphoma. Biology of Blood and Marrow Transplantation 2017 23, 1241-1249DOI: (10.1016/j.bbmt.2017.05.003) Copyright © 2017 Terms and Conditions

Figure 2 Novel niche pathways in HSPC mobilization. 1. CXCR4 receptors on HSCs interact with chemokine SDF-1. A disruption in this interaction causes mobilization (as modulated by G-CSF and plerixafor). Conversely, the S1P gradient draws HSCs peripherally. Hence, S1P agonists are hypothesized to cause mobilization. 3. Integrin receptor VLA-4 on HSCs interacts with VCAM-1 on niche vascular endothelial cells. VLA-4 antagonists mediate mobilization. 4. NSAIDs block PGE2-EP4 interactions to induce mobilization with G-CSF. PTH agonists (5), antagonists of endogenous HSPG (6), and nitric oxide inhibitors activating niche procoagulant pathways (7) activate novel HSC mobilization pathways. PTH indicates parathyroid hormone; CXCR-4, C-X-C chemokine receptor type 4; HSPG, heparan sulfate proteoglycans; PGE2, prostaglandin E2; EP4, prostaglandin E2 receptor 4; NSAIDS, nonsteroidal anti-inflammatory drugs; S1P, spingosine-1-phosphate; VLA-4, very late antigen-4; VCAM, vascular cell adhesion molecule. Biology of Blood and Marrow Transplantation 2017 23, 1241-1249DOI: (10.1016/j.bbmt.2017.05.003) Copyright © 2017 Terms and Conditions

Figure 3 Novel niche pathways in UCB HSPC expansion. Hematopoietic cytokines (1) were found to be permissive but not sufficient as stand-alone expanders. BM niche mimicking strategies, such as use of MSCs (2) and notch ligand (3), have resulted in short-term multilineage reconstitution. Newer small molecules, such as SR1 and NAM (4), have shown more promise with long-term multilineage reconstitution. MSC indicates mesenchymal stromal cells; SR1, StemReginin1; NAM, nicotinamide. Biology of Blood and Marrow Transplantation 2017 23, 1241-1249DOI: (10.1016/j.bbmt.2017.05.003) Copyright © 2017 Terms and Conditions