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Chapter 14 Interactions Between Hematopoietic Stem and Progenitor Cells and the Bone Marrow 151

Relevance to Clinical Hematology—cont’d

Clearly, because BMT is used increasingly in elderly adults and patients to achieve transient engraftment until the CB cells reconstitute the BM.
previously exposed to intense chemotherapy, novel approaches for In addition, circumventing this inherent limitation of CB use may be
optimizing mobilization are warranted. Several promising approaches achieved by improving HSPC homing potential. For instance, inhibition of
are looming over the clinical horizon; among them are novel mobilization CD26 allows augmented engraftment of stem cells to the recipient’s BM.
agents such as AMD3465, SB-251353, T140, and PTH acting in its Upregulation of CXCR4 by PGE 2 stimulation increases SDF-1 chemoat-
capacity as a pivotal regulator of hematopoietic niches. Additional avenues traction to the BM. Another pathway is activated by CD44 glycosylation,
to be explored in this area include the use of cord blood, which at present which may enhance navigation of treated MSCs to the BM. Taking into
is limited to pediatric patients and adults of low body weight because of consideration bone and BM niche integrity, influencing factors such as
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the low number of CD34 progenitors contained in each CB unit. For this age, timing of mobilization, and interplay among different mobilizing
reason, the major disadvantage of CB transplantation in adult patients is agents may be crucial in optimizing HSPC yield after mobilization, as
delayed engraftment. Approaches aimed at overcoming delayed engraft- well as their homing after transplantation. This approach might lead to
ment with CB transplantation include double-CB transplants or, together advanced development of new safe and efficient therapeutic strategies
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with mobilized or BM-derived CD34 cell infusion from a matched donor, for HSPC transplantation protocols.
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