Abstract
Models of mice carrying a human immune system, so-called humanized mice, are used increasingly as preclinical models to bridge the gap between model organisms and human beings. Challenges of the humanized mouse model include finding suitable sources for human hematopoietic stem cells (HSC) and reaching sufficient engraftment of these cells in immunocompromised mice. In this study, we compared the use of CD34+ HSC from cord blood (CB) vs HSC from adult mobilized peripheral blood. Furthermore, we developed a simple and highly specific test for donor identification in humanized mice by applying the detection method of short tandem repeats (STR). It was found that, in vitro, CB-derived and adult HSC show comparable purity, viability, and differentiation potential in colony-forming unit assays. However, in vivo, CB-derived HSC engrafted to a significantly higher extent in NOD.Cg-Prkdcscid IL2rγtm1Wjl /SzJ (NSG) mice than adult HSC. Increasing the cell dose of adult HSC or using fresh cells without cryopreservation did not improve the engraftment rate. Interestingly, when using adult HSC, the percentage of human cells in the bone marrow was significantly higher than that in the peripheral blood. Using the STR-based test, we were able...Continue Reading
References
Nov 27, 1999·Blood Cells, Molecules & Diseases·O BelvedereA Degrassi
Mar 21, 2000·Bone Marrow Transplantation·C De BruynD Bron
Aug 10, 2000·Molecular Biotechnology·C Hohoff, B Brinkmann
Sep 10, 2003·Experimental Hematology·Takuya MatsumuraSonoko Habu
Nov 27, 2004·Klinische Pädiatrie·S SchönbergerD Dilloo
May 21, 2008·Current Protocols in Immunology·Todd PearsonLeonard D Shultz
Jun 16, 2009·Human Immunology·Christin M LepusMartha J Harding
Oct 17, 2012·PloS One·Johanna ScholbachFranziska Lange
Jan 18, 2013·Science Translational Medicine·Jian ZhengWenwei Tu
Feb 27, 2013·Infection and Immunity·Wolfgang ErnstAnja K Wege
Mar 19, 2014·Nature Biotechnology·Anthony RongvauxRichard A Flavell
Aug 21, 2016·Blood·Yasuyuki SaitoMarkus G Manz
Aug 26, 2016·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Nadja HilgerStephan Fricke
Jun 10, 2017·Journal of Cellular Physiology·Ryoji ItoMamoru Ito
Aug 24, 2017·Cell Reports·Nigel G KooremanJoseph C Wu
Nov 9, 2018·Frontiers in Immunology·Nadja HilgerStephan Fricke
Mar 9, 2019·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Leonard D ShultzMichael A Brehm
Jun 5, 2019·Nature Immunology·Todd M AllenMercy PrabhuDas
Jun 11, 2019·Frontiers in Immunology·Lilly StahlStephan Fricke