Abstract:
BACKGROUND:Thrombocytopenia is a serious side effect following high-dose chemotherapy or whole-body irradiation. For many patients, a hematopoietic stem cell (HSC) transplant is required as part of the treatment or to restore the integrity of the hematopoietic system. In this article, we first review the origin of thrombocytopenia in the context of umbilical cord blood (UCB) transplantation and current cellular therapies developed to overcome this condition. Results obtained in recent clinical trials and in the laboratory using a mouse-based xenograft model were also discussed. Second, we investigate the kinetic of human platelet production in two immunodeficient mouse strains transplanted with UCB cells to determine which of the two is better suited to measure the thrombopoietic potential of human hematopoietic cells. STUDY DESIGN AND METHODS:NOD/SCID/IL2Rγ(null) or NOD.CB17-Prkdcscid/NcrCrl (NOD/SCID) mice were transplanted with ex vivo expanded UCB cells. Human platelet levels and marrow engraftments were measured by cytometry analyses. RESULTS:Human platelets appeared earlier and at greater levels in the NOD/SCID/IL2Rγ(null) mouse strain. Consistent with these results and previous reports, human marrow engraftment was also greater in the IL2Rγ(null) -based NOD/SCID mice. CONCLUSION:The NOD/SCID/IL2Rγ(null) mouse strain is an ideal choice for preclinical studies aimed at measuring the in vivo thrombopoietic potential of human HPCs. Exploitation of such a model should facilitate the development of new cellular therapies aimed at improving hematological recoveries following HSC transplantation.
journal_name
Transfusionjournal_title
Transfusionauthors
Pineault N,Boyer Ldoi
10.1111/j.1537-2995.2011.03369.xsubject
Has Abstractpub_date
2011-11-01 00:00:00pages
72S-81Seissn
0041-1132issn
1537-2995journal_volume
51 Suppl 4pub_type
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