New Discoveries May Make Stem Cell Expansion Possible

[Guest guest]

Bone Marrow Transplantation (2007) 39, 11–23.

doi:10.1038/sj.bmt.1705538

Ex vivo expansion of umbilical cord blood stem cells for

transplantation: growing knowledge from the hematopoietic niche

C C Hofmeister1, J Zhang1, K L Knight1, P Le1 and P J Stiff1

1Cardinal Bernardin Cancer Center, Loyola University Medical Center,

Maywood, IL, USA

Correspondence: Dr PJ Stiff, Cardinal Bernardin Cancer Center,

Loyola University Medical Center, 2160 S First Avenue, Building 112,

Room 240, Maywood, IL 60153, USA. E-mail: pstiff@...

Received 12 October 2006; Accepted 12 October 2006.

Abstract

Umbilical cord blood transplantation (UCBT) in adults is limited by

the small number of primitive hematopoietic stem cells (HSC) in each

graft, resulting in delayed engraftment post transplant, and both

short- and long-term infectious complications.

Initial efforts to expand UCB progenitors ex vivo have resulted in

expansion of mature rather than immature HSC, confounded by the

inability to accurately and reliably measure long-term

reconstituting cells. Ex vivo expansion of UCB HSC has failed to

improve engraftment because of resulting defects that promote

apoptosis, disrupt marrow homing and initiate cell cycling.

Here we discuss the future of ex vivo expansion, which we suggest

will include the isolation of immature hematopoietic progenitors on

the basis of function rather than surface phenotype and will employ

both cytokines and stroma to maintain and expand the stem cell

niche. We suggest that ex vivo expansion could be enhanced by

manipulating newly discovered signaling pathways (Notch, Wnt, bone

morphogenetic protein 4 and Tie2/angiopoietin-1) and intracellular

mediators (phosphatase and tensin homolog and glycogen synthase

kinase-3) in a manner that promotes HSC expansion with less

differentiation.

Improved methods for ex vivo expansion will make UCBT available to

more patients, decrease engraftment times and allow more rapid

immune reconstitution post transplant.

Read the full-text article at:

http://m1e.net/c?39915698-huTfe2N4f/aPE%402153106-rhaNH6ZTE9P92