ABSTRACT
HOXB4 Protein Transfer ...................................................................... 263
15.3.1 Amplification of the Production of Total Cells and
Clonogenic Progenitors (CFCs) in Long-Term Coculture
of CD34C Cells with hHOXB4-Producing MS-5 Cells ........ 263
15.3.2 Amplification of CFCs and LTC-ICs in Long-Term
Cocultures of CD34CCD38low Cells with
hHOXB4-Producing MS-5 Cells ............................................ 264
15.3.3 Enhanced NOD-SCID Mice Engraftment and
Repopulating Activity of HOXB4-Expanded Human
Primitive Hematopoietic Cells ................................................ 265
15.4 Discussion and Conclusions .................................................................. 266
Acknowledgments ............................................................................................ 268
References ........................................................................................................ 268
All blood cells derive from multipotent hematopoietic stem cells (HSCs) through
lineage-specific committed progenitors that undergo terminal differentiation
following a single pathway. As in most stem cells, HSCs represent a very rare
population and have the capacity to both long-term selfrenew and differentiate,
according to body needs.1,2 Hematopoiesis is a process tightly regulated by a series
of signals, either endogenous (intrinsic regulation through transcription factors) or
exogenous provided by the stem cell environment, mainly in so-called “bone
marrow hematopoietic niches” (extrinsic regulation) (Figure 15.1). Difficulties
in identifying and isolating HSCs are not only related to their scarcity, but also to
their heterogeneity in both their phenotype and potentialities and to the absence of a
precise localization inside the bone marrow. Therefore, HSC-enrichment techniques
in humans are based on their phenotypic characteristics (cell surface antigens such
as CD34 and CD38) and metabolic characteristics (dye efflux of Hoechst 33342).
