Engraftment Kinetics of Human Cord Blood and Murine Fetal Liver Stem Cells Following In Utero Transplantation into Immunodeficient Mice

Schoeberlein, Andreina; Schatt, Stephan; Troeger, Carolyn; Surbek, Daniel; Holzgreve, Wolfgang; Hahn, Sinuhe

doi:10.1089/scd.2004.13.677

Cited by 18 publications

(9 citation statements)

References 20 publications

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“…Similar results have also been observed in other species, most notably, humans (4) and cotton top tamarin (5). In the past decade, the multilineage hematopoietic chimerism in fetal mouse was well documented after adult bone marrow (BM) derived HSC transplantation (6,7) and human cord blood transplantation (8,9). In addition, we established an experimental model of in utero transplantation of human hematopoietic stem cells into fetal goats under B-scan ultrasonography.…”

Section: Introductionsupporting

confidence: 77%

In utero transplantation of human hematopoietic stem/progenitor cells partially repairs injured liver in mice

Qian

Wang²,

Wang³

et al. 2006

Int J Mol Med

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Abstract. The aim of this study is to establish a novel mouse model with high achievement and chimerism by in utero transplantation of human hematopoietic stem/progenitor cells and to explore the possibility that human adult hematopoietic stem/progenitor cells can differentiate into hepatocyte-like cells and partially repair the liver damage induced by carbon tetrachloride (CCl 4 ). Mononuclear cells (MNCs) were isolated from fresh human umbilical cord blood (hUCB) and CD34 + cells were enriched from the MNCs by magnetic cell isolation. These cells were injected respectively into the fetal mice at 11-13 days of gestation. At one month after birth, the specific markers of human cells, human ·-satellite sequence (h17·), CD14, CD34, CD45, and GPA were detected by PCR and FACS. At three and six months after birth, the established human-mouse chimeras were administered with CCl 4 by intraperitoneal injection. The biochemical markers (ALT, AST, ALP, albumin) in serum were determined and human hepatocyte-specific proteins, such as human albumin, hepatocyte nuclear factor-4, hepatocyte specific antigen, tryptophan 2,3-dioxygenase and · fetoprotein were analyzed by PCR, RT-PCR, real-time PCR and immunohistochemistry staining, respectively. More than 77% of recipients demonstrated human-mouse chimera. Significantly, hUCB hematopoietic stem/progenitor cells may differentiate into human hepatocytelike cells with evidence of the expression of human hepatocytespecific proteins as well as partially repair or protect liver damage induced by CCl 4 . The mouse model described in this article provides a useful tool for the studies of regeneration of human hepatocyte-like cells from adult hematopoietic stem/ progenitor cells as well as facilitates the therapeutic potential for liver diseases or damage by in utero transplantation.

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Section: Introductionsupporting

confidence: 77%

In utero transplantation of human hematopoietic stem/progenitor cells partially repairs injured liver in mice

Qian

Wang²,

Wang³

et al. 2006

Int J Mol Med

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“…The resulting “humanized” mice serve as model organisms for a variety of disorders and for pre-clinical research [1], [3], [6], [7]. Introduction of hematopoietic stem cells into immunodeficient mice, for example, allows for the in vivo study of their differentiation into the various components of human blood [7]–[11]. Humanized mice have aided in the development of gene therapies and cell-based therapies for hematopoietic disorders in humans [7], [12]–[26].…”

Section: Introductionmentioning

confidence: 99%

Identification of an Astrovirus Commonly Infecting Laboratory Mice in the US and Japan

Kondov

Hayashimoto

et al. 2013

PLoS ONE

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Mice (Mus musculus) are the most commonly used laboratory animals. Viral metagenomics on tissues of immunodeficient mice revealed sequences of a novel mammalian astrovirus. Using PCR, we screened mice from 4 breeders, 4 pharmaceutical companies, 14 research institutes and 30 universities in the US and Japan. Mice from one US breeder tested positive while none from Japanese breeders were positive for MuAstV. Mice in over half of the universities (19/30), institutes (7/14) and pharmaceutical animal facilities (2/4) investigated revealed the presence of MuAstV. Nine mice strains tested positive including both immunodeficient strains (NSG, NOD-SCID, NSG-3GS, C57BL6-Timp-3 −/−, and uPA-NOG) and immunocompetent strains (B6J, ICR, Bash2, BALB/c). Our data indicates that MuAstV has a wide geographical, institutional and host strain distribution. Comparison of the MuAstV RdRp sequences showed numerous mutations indicating ongoing viral divergence in different facilities. This study demonstrates the need for metagenomic screening of laboratory animals to identify adventitious infections that may affect experimental outcomes.

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“…In a xenogeneic model, donor HSCs rapidly diminish following IUHSCT due to lack of cross-species reactivity from self-renewal and differentiation cues in the host’s environment (38). Others have demonstrated that transplanted human MSCs differentiate in the BM niche in mice into pericytes, myofibroblasts, BM stromal cells, osteocytes in bone, bone-lining osteoblasts, and endothelial cells, which resulted in enhanced human HSC engraftment in adult recipients (20).…”

Section: Discussionmentioning

confidence: 99%

Influence of a dual-injection regimen, plerixafor and CXCR4 on in utero hematopoietic stem cell transplantation and engraftment with use of the sheep model

et al. 2014

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Background Inadequate engraftment of hematopoietic stem cells (HSCs) following in-utero HSC transplantation (IUHSCT) remains a major obstacle for the prenatal correction of numerous hereditary disorders. HSCs express CXCR4 receptors that allow homing and engraftment in response to SDF1 ligand present in the bone marrow (BM) stromal niche. Plerixafor, a mobilization drug, works through the interruption of the CXCR4-SDF1 axis. Methods We used the fetal sheep large animal model to test our hypotheses that: a) by administering plerixafor in-utero before performing IUHSCT to release fetal HSCs and thus vacating recipient HSC niches, b) by using human mesenchymal stromal/stem cells (MSCs) to immunomodulate and humanize the fetal BM niches, and c) by increasing the CXCR4+ fraction of CD34+ HSCs, we could improve engraftment. Human cord blood-derived CD34+ cells and human bone marrow-derived MSCs were used for these studies. Results When MSCs were transplanted one week prior to CD34+ cells with plerixafor treatment, we observed 2.80% donor hematopoietic engraftment. Combination of this regimen with additional CD34+ cells at the time of MSC infusion increased engraftment levels to 8.77%. Next, increasing the fraction of CXCR4+ cells in the CD34+ population albeit transplanting at a late gestation age was not beneficial. Our results show engraftment of both lymphoid and myeloid lineages. Discussion Prior MSC and HSC cotransplantation followed by manipulation of the CXCR4-SDF1 axis in IUHSCT provides an innovative conceptual approach for conferring competitive advantage to donor HSCs. Our novel approach could provide a clinically relevant approach for enhancing engraftment early in the fetus.

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Engraftment Kinetics of Human Cord Blood and Murine Fetal Liver Stem Cells Following In Utero Transplantation into Immunodeficient Mice

Cited by 18 publications

References 20 publications

In utero transplantation of human hematopoietic stem/progenitor cells partially repairs injured liver in mice

In utero transplantation of human hematopoietic stem/progenitor cells partially repairs injured liver in mice

Identification of an Astrovirus Commonly Infecting Laboratory Mice in the US and Japan

Influence of a dual-injection regimen, plerixafor and CXCR4 on in utero hematopoietic stem cell transplantation and engraftment with use of the sheep model

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