In-Uthro Transplantation of Fetal Liver Haemopoietic Stem Cells in Monkeys

Harrison, M. R.; Crombleholme, T. M.; Tarantal, Alice F.; Slotnick, R. Nathan; Golbus, M S; Zanjani, ED

doi:10.1016/s0140-6736(89)92036-9

Cited by 126 publications

(61 citation statements)

References 13 publications

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“…While mouse and human adult stem cells were in utero transplanted into the fetus at a couple of days of gestation, adult engraftment of allogeneic and xenogeneic cells were frequently detectable in hematopoietic and nonhematopoietic organs, including PB, BM, spleen, liver, kidney, thymus, muscle, lung, gut, stomach, skin, brain and heart of the recipient sheep [5,7] , mice [6,22] , monkeys [3] , pigs [2] and goats [8,23] , and rats in this study, although the pattern of allogeneic and xenogeneic transplanted cell distribution over all tissues examined in individual recipient differed.…”

Section: Multiorgan Engraftment and Unevenly Distribution Of Donor-dementioning

confidence: 99%

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Generation of human/rat xenograft animal model for the study of human donor stem cell behaviorsin vivo

Sun

Xiao²,

Pan³

et al. 2007

WJG

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AIM:To accurately and realistically elucidate human stem cell behaviors in vivo and the fundamental mechanisms controlling human stem cell fates in vivo , which is urgently required in regenerative medicine and treatments for some human diseases, a surrogate human-rat chimera model was developed. METHODS:Human-rat chimeras were achieved by in utero transplanting low-density mononuclear cells from human umbilical cord blood into the fetal rats at 9-11 d of gestation, and subsequently, a variety of methods, including flow cytometry, PCR as well as immunohistochemical assay, were used to test the human donor contribution in the recipients.

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Section: Multiorgan Engraftment and Unevenly Distribution Of Donor-dementioning

confidence: 99%

“…To address these issues, there are active sustaining efforts to pursue developing human/animal xenograft models (including mice, sheep, goats, monkeys and pigs) to in vivo study the related fundmental mechanisms [2][3][4][5][6][7][8] .…”

Section: Introductionmentioning

confidence: 99%

Generation of human/rat xenograft animal model for the study of human donor stem cell behaviorsin vivo

Sun

Xiao²,

Pan³

et al. 2007

WJG

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“…Thus, the need for immunosuppression and myeloablation used for postnatal transplantation can be avoided. Allogeneic and xenogeneic chimerism has been generated by in utero transplantation procedures, and fetal engraftment of allogeneic and xenogeneic HSC has been tested in mouse, sheep, and monkey and more recently in pigs and goats (8)(9)(10)(11)(12). Questions remain regarding the engraftment, homing, and differentiation of allogeneic or xenogeneic HSC, as well as the gene expression of the engrafted cells in different tissues of the recipients.…”

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confidence: 99%

Multiorgan engraftment and differentiation of human cord blood CD34 ⁺ Lin ⁻ cells in goats assessed by gene expression profiling

Zeng

Chen

Baldwin

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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To investigate multitissue engraftment of human primitive hematopoietic cells and their differentiation in goats, human CD34 ؉ Lin ؊ cord blood cells transduced with a GFP vector were transplanted into fetal goats at 45-55 days of gestation. GFP ؉ cells were detected in hematopoietic and nonhematopoietic organs including blood, bone marrow, spleen, liver, kidney, muscle, lung, and heart of the recipient goats (1.2-36% of all cells examined). We identified human ␤2 microglobulin-positive cells in multiple tissues. GFP ؉ cells sorted from the perfused liver of a transplant goat showed human insulin-like growth factor 1 gene sequences, indicating that the engrafted GFP ؉ cells were of human origin. A substantial fraction of cells engrafted in goat livers expressed the human hepatocyte-specific antigen, proliferating cell nuclear antigen, albumin, hepatocyte nuclear factor, and GFP. DNA content analysis showed no evidence for cellular fusion. Long-term engraftment of GFP ؉ cells could be detected in the blood of goats for up to 2 yr. Microarray analysis indicated that human genes from a variety of functional categories were expressed in chimeric livers and blood. The human͞goat xenotransplant model provides a unique system to study the kinetics of hematopoietic stem cell engraftment, gene expression, and possible stem cell plasticity under noninjured conditions. hematopoietic stem cell ͉ transplantation ͉ plasticity ͉ microarray

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“…25,26,28,29 It appears that significant chimerism is achieved only when the donor HSCs or their progeny have a competitive advantage over the host cells. 30 Allogeneic and xenogeneic IUT in large animals has had mixed results with some studies achieving clinically significant levels of chimerism [31][32][33][34][35][36] whereas others have failed to engraft donor cells above 1%. 37,38 An explanation for the disparate results in the various animal models is not apparent.…”

Section: Discussionmentioning

confidence: 99%

Transplantation of a fetus with paternal Thy-1+CD34+cells for chronic granulomatous disease

Muench

Rae²,

Bárcena

et al. 2001

Bone Marrow Transplant

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Summary:A fetus diagnosed with X-linked chronic granulomatous disease was transplanted with Thy-1 ؉ CD34 ؉ cells of paternal origin. The transplant was performed at 14 weeks gestation by ultrasound guided injection into the peritoneal cavity. The fetus was delivered at 38 weeks gestation after an otherwise uneventful pregnancy. Umbilical cord blood was collected and used to determine the level of peripheral blood chimerism as well as levels of functional engrafted cells. Flow cytometry was used to detect donor leukocytes identified as HLA-A2 ؊ B7 ؉ cells, whereas recipient cells were identified as HLA-A2 ؉ B7 ؊ cells. No evidence of donor cell engraftment above a level of 0.01% was found. PCR was used to detect HLA-DRB1*15 ؉ donor cells among the recipient's HLA-DRB1*15 ؊ cells, but no engraftment was seen with a sensitivity of 1:1000. The presence of functional, donor-derived neutrophils was assessed by flow cytometry using two different fluorescent dyes that measure reactive oxygen species generated by the phagocyte NADPH oxidase. No evidence of paternal-derived functional neutrophils above a level of 0.15% was observed. Peripheral blood and bone marrow samples were collected at 6 months of age. Neither sample showed engraftment by HLA typing using both flow cytometry and PCR. Functional phagocytes were also not observed. Furthermore, no indication of immunological tolerance specific for the donor cells was indicated by a mixed lymphocyte reaction assay performed at 6 months of age. While there appears to be no engraftment of the donor stem cells, the transplant caused no harm to the fetus and the child was healthy at 6 months of age. Analyses of fetal tissues, obtained from elective abortions, revealed that CD3 ؉ T cells and CD56 ؉ CD3 ؊ NK cells are present in the liver at 8 weeks gestation and in the blood by 9 weeks gestation. The presence of these lymphocytes may contribute to the

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In-Uthro Transplantation of Fetal Liver Haemopoietic Stem Cells in Monkeys

Cited by 126 publications

References 13 publications

Generation of human/rat xenograft animal model for the study of human donor stem cell behaviorsin vivo

Generation of human/rat xenograft animal model for the study of human donor stem cell behaviorsin vivo

Multiorgan engraftment and differentiation of human cord blood CD34 ⁺ Lin ⁻ cells in goats assessed by gene expression profiling

Transplantation of a fetus with paternal Thy-1+CD34+cells for chronic granulomatous disease

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In-Uthro Transplantation of Fetal Liver Haemopoietic Stem Cells in Monkeys

Cited by 126 publications

References 13 publications

Generation of human/rat xenograft animal model for the study of human donor stem cell behaviorsin vivo

Generation of human/rat xenograft animal model for the study of human donor stem cell behaviorsin vivo

Multiorgan engraftment and differentiation of human cord blood CD34 + Lin − cells in goats assessed by gene expression profiling

Transplantation of a fetus with paternal Thy-1+CD34+cells for chronic granulomatous disease

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Multiorgan engraftment and differentiation of human cord blood CD34 ⁺ Lin ⁻ cells in goats assessed by gene expression profiling