We recently developed a clinical grade ex vivo cord blood (CB) expansion procedure
enabling a massive amplification of hematopoietic progenitors without any loss of
stem cell potential as revealed on the basis of serial engraftment of Nod/SCID mice
(Ivanovic et al, Cell Transplant. 2011). This procedure, in line with our concept
“Oxygen Stem Cell Paradigm” (Ivanovic, J Cell Physiol 2009), is based on Day 14 liquid
cultures of CB CD34+ cells, in medium Macopharma HP01 (containing several antioxidant
molecules and nicotinamide) and in presence of Stem Cell Factor - SCF (100 ng/ml),
fms-Related Tyrosine Kinase 3 – Ligand - FLT3-ligand (100ng/ml), Megakaryocyte Growth
and Developmental Factor - MGDF (100 Ng/ml) (these two cytokines acting in favor of
HIF-1alpha transcript stabilization) and Granulocyte – Colony Stimulating Factor -G-CSF
(10 Ng/ml). This cocktail had to be modified due to the commercially unavailability
of clinical grade MGDF molecule. So, MGDF was replaced by Thrombopoietin - TPO in
five-fold lower dose (20 ng/ml) and culture time was reduced to 12 days (Duchez et
al Cell Transplant 2012). That way, a mean expansion fold of 400, 80, and 150 was
obtained for total cells, CD34+ cells and Colony Forming Cells – CFC, respectively.
This amplification was associated with a slight enhancing effect on stem cells (Scid
Repopulating Cells - SRC). These are the ultimate pre-clinical modifications of a
clinical grade expansion protocol which is already employed in an ongoing clinical
trial (adult allogeneic context) started in 2010). The preliminary results are encouraging
– rapid and durable hematopoietic reconstitution after injection of one ex vivo expanded
CB unit only.
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© 2014 Published by Elsevier Inc.