Recovery and Biodistribution of Ex Vivo Expanded Human Erythroblasts Injected into NOD/SCID/IL2Rγnull mice

Ex vivo expanded erythroblasts (EBs) may serve as advanced transfusion products provided that lodgment occurs in the macrophage-niche of the marrow permitting maturation. EBs expanded from adult and cord blood expressed the receptors (CXCR4, VLA-4, and P-selectin ligand 1) necessary for interaction...

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Main Authors: Barbara Ghinassi, Leda Ferro, Francesca Masiello, Valentina Tirelli, Massimo Sanchez, Giovanni Migliaccio, Carolyn Whitsett, Stefan Kachala, Isabelle Riviere, Michel Sadelain, Anna Rita Migliaccio
Format: Article
Language:English
Published: Wiley 2011-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.4061/2011/673752
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author Barbara Ghinassi
Leda Ferro
Francesca Masiello
Valentina Tirelli
Massimo Sanchez
Giovanni Migliaccio
Carolyn Whitsett
Stefan Kachala
Isabelle Riviere
Michel Sadelain
Anna Rita Migliaccio
author_facet Barbara Ghinassi
Leda Ferro
Francesca Masiello
Valentina Tirelli
Massimo Sanchez
Giovanni Migliaccio
Carolyn Whitsett
Stefan Kachala
Isabelle Riviere
Michel Sadelain
Anna Rita Migliaccio
author_sort Barbara Ghinassi
collection DOAJ
description Ex vivo expanded erythroblasts (EBs) may serve as advanced transfusion products provided that lodgment occurs in the macrophage-niche of the marrow permitting maturation. EBs expanded from adult and cord blood expressed the receptors (CXCR4, VLA-4, and P-selectin ligand 1) necessary for interaction with macrophages. However, 4-days following transfusion to intact NOD/SCID/IL2Rγnull mice, CD235apos EBs were observed inside CD235aneg splenic cells suggesting that they underwent phagocytosis. When splenectomized and intact NOD/SCID/IL2Rγnull mice were transfused using retrovirally labeled human EBs, human cells were visualized by bioluminescence imaging only in splenectomized animals. Four days after injection, human CD235apos cells were detected in marrow and liver of splenectomized mice but only in spleen of controls. Human CD235apos erythrocytes in blood remained low in all cases. These studies establish splenectomized NOD/SCID/IL2Rγnull mice as a suitable model for tracking and quantification of human EBs in vivo.
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spelling doaj-art-33fafcce1aa74af29415a67ab81bcca42025-02-03T01:32:02ZengWileyStem Cells International1687-966X1687-96782011-01-01201110.4061/2011/673752673752Recovery and Biodistribution of Ex Vivo Expanded Human Erythroblasts Injected into NOD/SCID/IL2Rγnull miceBarbara Ghinassi0Leda Ferro1Francesca Masiello2Valentina Tirelli3Massimo Sanchez4Giovanni Migliaccio5Carolyn Whitsett6Stefan Kachala7Isabelle Riviere8Michel Sadelain9Anna Rita Migliaccio10The Tisch Cancer Institute and Myeloproliferative Disease Research Consortium (MPD-RC), Mount Sinai School of Medicine, One Gustave L. Levy Place, P.O. Box 1079, New York, NY 10029, USACenter for Cell Engineering, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USACell Biology and Neuroscience, Istituto Superiore di Sanità, 00161 Rome, ItalyCell Biology and Neuroscience, Istituto Superiore di Sanità, 00161 Rome, ItalyCell Biology and Neuroscience, Istituto Superiore di Sanità, 00161 Rome, ItalyCell Biology and Neuroscience, Istituto Superiore di Sanità, 00161 Rome, ItalyThe Tisch Cancer Institute and Myeloproliferative Disease Research Consortium (MPD-RC), Mount Sinai School of Medicine, One Gustave L. Levy Place, P.O. Box 1079, New York, NY 10029, USACenter for Cell Engineering, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USACenter for Cell Engineering, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USACenter for Cell Engineering, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USAThe Tisch Cancer Institute and Myeloproliferative Disease Research Consortium (MPD-RC), Mount Sinai School of Medicine, One Gustave L. Levy Place, P.O. Box 1079, New York, NY 10029, USAEx vivo expanded erythroblasts (EBs) may serve as advanced transfusion products provided that lodgment occurs in the macrophage-niche of the marrow permitting maturation. EBs expanded from adult and cord blood expressed the receptors (CXCR4, VLA-4, and P-selectin ligand 1) necessary for interaction with macrophages. However, 4-days following transfusion to intact NOD/SCID/IL2Rγnull mice, CD235apos EBs were observed inside CD235aneg splenic cells suggesting that they underwent phagocytosis. When splenectomized and intact NOD/SCID/IL2Rγnull mice were transfused using retrovirally labeled human EBs, human cells were visualized by bioluminescence imaging only in splenectomized animals. Four days after injection, human CD235apos cells were detected in marrow and liver of splenectomized mice but only in spleen of controls. Human CD235apos erythrocytes in blood remained low in all cases. These studies establish splenectomized NOD/SCID/IL2Rγnull mice as a suitable model for tracking and quantification of human EBs in vivo.http://dx.doi.org/10.4061/2011/673752
spellingShingle Barbara Ghinassi
Leda Ferro
Francesca Masiello
Valentina Tirelli
Massimo Sanchez
Giovanni Migliaccio
Carolyn Whitsett
Stefan Kachala
Isabelle Riviere
Michel Sadelain
Anna Rita Migliaccio
Recovery and Biodistribution of Ex Vivo Expanded Human Erythroblasts Injected into NOD/SCID/IL2Rγnull mice
Stem Cells International
title Recovery and Biodistribution of Ex Vivo Expanded Human Erythroblasts Injected into NOD/SCID/IL2Rγnull mice
title_full Recovery and Biodistribution of Ex Vivo Expanded Human Erythroblasts Injected into NOD/SCID/IL2Rγnull mice
title_fullStr Recovery and Biodistribution of Ex Vivo Expanded Human Erythroblasts Injected into NOD/SCID/IL2Rγnull mice
title_full_unstemmed Recovery and Biodistribution of Ex Vivo Expanded Human Erythroblasts Injected into NOD/SCID/IL2Rγnull mice
title_short Recovery and Biodistribution of Ex Vivo Expanded Human Erythroblasts Injected into NOD/SCID/IL2Rγnull mice
title_sort recovery and biodistribution of ex vivo expanded human erythroblasts injected into nod scid il2rγnull mice
url http://dx.doi.org/10.4061/2011/673752
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