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Fast But Durable Megakaryocyte Repopulation and Platelet Production in NOD/SCID Mice Transplanted with Ex-Vivo Expanded Human Cord Blood CD34⁺ Cells

^a Department of Oncological Sciences, University of Torino Medical School,
^b Division of Clinical Oncology, Institute for Cancer Research and Treatment, Candiolo, Torino, Italy;
^c The Pediatric Department, University of Torino Medical School, Torino, Italy

Key Words. Cord blood • CD34⁺ cell expansion • NOD/SCID • Megakaryocyte engraftment

Correspondence: Wanda Piacibello, M.D., University of Torino Medical School, Department of Oncological Sciences, Institute for Cancer Research and Treatment, Laboratory of Clinical Oncology, Prov. 142, 10060 Candiolo, Torino, Italy. Telephone: 39-011-9933349; Fax: 39-011-9933522; e-mail: wanda.piacibello{at}ircc.it

We have previously established a stroma-free culture with Flt-3 ligand (FL), stem cell factor (SCF), and thrombopoietin (TPO) that allows the maintenance and the expansion for several weeks of a cord blood (CB) CD34⁺ cell population capable of multilineage and long-lasting hematopoietic repopulation in non-obese diabetic/ severe combined immunodeficient (NOD/SCID) mice.

In this work the kinetics of megakarocyte (Mk)-engraftment that is often poor and delayed in CB transplantation, and human platelet (HuPlt) generation in NOD/SCID mice of baseline CD34⁺ cells (b34⁺), and of CD34⁺ cells reisolated after a 4-week expansion with FL+SCF+TPO (4w34⁺) were compared.

With b34⁺ cells Mk-engraftment was first seen at week 3 (CD41⁺: 0.4%); 4w34⁺ cells allowed a more rapid Mk-engraftment (at weeks 2 and 3 the CD41⁺ cells were 0.3% and 0.8%). Circulating HuPlts were first seen at weeks 2 and 1, respectively.

Mk-engraftment levels of b34⁺ and 4w34⁺ cells 6–8 weeks after transplantation were similar (12 ± 3.5 versus 15 ± 5% CD45⁺; 1.3 ± 0.5 versus 1.8 ± 0.5% CD41⁺ cells). Also serial transplant experiments were performed with expanded and reselected CB cells. In secondary and tertiary recipients the Mk population was detected with bone marrow fluorescence-activated cell sorter analysis; these experiments indicate the effective long-term repopulation of expanded cells. Selected CD34⁺ cells after a 4-week expansion with FL+SCF+TPO are more efficient in Mk engraftment than the same number of unmanipulated cells.

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