Ex vivo culture of human CD34+ cord blood cells with thrombopoietin (TPO) accelerates platelet engraftment in a NOD/SCID mouse model.
OBJECTIVE
Hematopoietic recovery, in particular platelet reconstitution, can be severely delayed after transplantation with cord blood (CB) stem cells (SC). Expansion of CB SC may be one way to improve the recovery, but there is concern that ex vivo expansion compromises the repopulating ability of SC.


METHODS
We used a short-term expansion protocol with TPO as single growth factor. The expanded cells were tested in the NOD/SCID mouse model and both platelet recovery and repopulation capacity were examined and compared with unexpanded CD34+ CB cells of the same CB donor.


RESULTS
Platelet recovery started 1 week earlier in mice transplanted with TPO-expanded CD34+ cells and at days 5 and 8 after transplantation, 6.2 +/- 2.6 and 13.9 +/- 6.7 plt/microL were observed, respectively. At similar time intervals 0.0 and 1.5 +/- 0.2 plt/microL respectively were detected in mice receiving the unmanipulated CD34+ grafts. This was accompanied by a higher number of CFU-Mk in the bone marrow (BM) 7 days after transplantation. Moreover, the BM engraftment and the lineage differentiation of human cells at 6 weeks after transplantation was similar, suggesting that long-term engraftment was not compromised by the expansion procedure.


CONCLUSIONS
Ex vivo expansion with TPO as single growth factor results in an accelerated platelet recovery in NOD/SCID mice and appears not to affect the long-term repopulation capacity.
van Hensbergen
Yvette
Y
Sanquin Blood Bank, Department of Research and Education, Leiden, The Netherlands.
Schipper
Laurus F
LF
Brand
Anneke
A
Slot
Manon C
MC
Welling
Mick
M
Nauta
Alma J
AJ
Fibbe
Willem E
WE
D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology*; D001792:Blood Platelets / Q000166:cytology*; D019070:Cell Lineage; D002478:Cells, Cultured; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D023421:Models, Animal
D018952:Antigens, CD34