June 30, 2011 10:26 9in x 6in Stem Cells: From Mechanisms to Technologies b1235-ch06 1st Reading 6 1 The Importance of Physiologically Inspired Physicochemical Parameters on Hematopoietic Stem-Cell Maintenance and Lineage-Specific Differentiation in Ex Vivo Cultures Stephan Lindsey and Eleftherios T. Papoutsakis 2 6.1. Introduction 3 6.1.1. The thesis for the chapter 4 Stem cell localization reflects the needs of these cells for maintenance, renewal 5 and need-driven differentiation. The stem cell niche is dictated not only by cells 6 that co-occupy the body locale of the stem cells, but also by the physicochemical 7 parameters or nutrient availability of that locale, including the pH, pO 2 , physical 8 forces due to flow (or lack of thereof), and the amount (i.e. abundance, lack or limited 9 supply) of nutrient and growth factors. These issues have largely remained out of 10 the radar screen of modern stem cell biology and bioengineering, but they now 11 emerge as potent, if not indispensable, modulators of stem cell fate. Here we focus 12 on issues associated with ex vivo expansion of hematopoietic stem and progenitor 13 cells (HSPCs). 14 6.1.2. Hematopoietic culture applications 15 and challenges, and the importance 16 of the physicochemical parameters 17 of the stem cell niche 18 Stem and progenitor cells from the bone marrow (BM), mobilized peripheral blood 19 (mPB), or cord blood (CB) can be used to restore hematopoietic activity in patients 20 whose BM has been ablated by chemotherapy (Bertolini et al., 1997; Brugger et al., 21 1