Cellular-based therapies to prevent or reduce thrombocytopenia.

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

Transfusion

journal_title

Transfusion

authors

Pineault N,Boyer L

doi

10.1111/j.1537-2995.2011.03369.x

subject

Has Abstract

pub_date

2011-11-01 00:00:00

pages

72S-81S

eissn

0041-1132

issn

1537-2995

journal_volume

51 Suppl 4

pub_type

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