Human hepatocytes in mice receiving pre-immune injection with human cord blood cells

Turrini, Paolo; Monego, Giovanni; González, José Emilio Caballero; Cicuzza, S.; Bonanno, Giuseppina; Zelano, Giovanni; Rosenthal, Nadia; Paonessa, Giacomo; Laufer, Ralph; Padrón, Julio Rodríguez

doi:10.1016/j.bbrc.2004.10.204

Cited by 24 publications

(20 citation statements)

References 39 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: 50%

“…Many authors have reported that multipotent stem cells of bone marrow or umbilical cord blood gave rise to hepatocytes, endothelial cells and muscle (9,(11)(12)(13). These experiments have demonstrated that multipotent stem cells (or their progeny) have the characteristics of unexpected plasticity or transdetermination when located in ectopic environments.…”

Section: Introductionmentioning

confidence: 99%

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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: 50%

Section: Introductionmentioning

confidence: 99%

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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“…In utero or blastocyst transplantation of hSCs from multiple sources can form all possible donor-derived human cell types in the recipient liver, which in turn constitute human hepatic parenchymal and stromal components [2,6,[18][19][20]22,24] . In contrast to the immunodeficient mice harboring a humanized liver, HAC in liver humanization possess and potential human immune system can be reconstituted with donor-derived human differentiated cells (data not shown).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to the immunodeficient mice harboring a humanized liver, HAC in liver humanization possess and potential human immune system can be reconstituted with donor-derived human differentiated cells (data not shown). Besides the functional donor-derived human mature HLCs positive for human Alb, AFP, HNF-4, etc, throughout the host liver parenchyma, an "ideal humananimal chimeric liver" can also synthesize and secrete human Alb, ALT, AST and ALP into the circulation of host animals [2,6,[18][19][20]22,24] . Our findings demonstrate that donor-derived human mature hepatocytes, endothelial and biliary duct cells in human-rat chimeric liver, constitute the "humanized hepatic functional units" in animal liver [2,19,20] .…”

Section: Discussionmentioning

confidence: 99%

“…In utero transplantation of hSCs, such as human hematopoietic stem cells and mesenchymal stem cells, into fetal sheep [2,6] , goats [24] , rats [19,20] , and mice [18,22] or blastocyst transplantation of hSCs into mice [22] , has led to the establishment of non-injury human-animal xenograft models carrying humanized liver, in which a significant number of functional donor-derived human mature hepatocyte-like cells (HLCs) stained positively for human albumin (Alb), alpha fetoprotein (AFP) and hepatocyte nuclear factor-4 can be found. Moreover, such a "HAC liver" can also produce and secrete human Alb, alanine aminotransferase (ALT), aspartic acid aminotransferase (AST) and alkaline phosphatase (ALP) in the circulation of host mice [18] and sheep [2,6] that have undergone transplantation.…”

Section: Introductionmentioning

confidence: 99%

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Phenotypic changes of human cells in human-rat liver during partial hepatectomy-induced regeneration

Sun

Xiao²,

Li³

et al. 2009

WJG

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Implication of hepatic stem cells in functional liver repopulation

Christ

Pelz

2012

Cytometry Pt A

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The liver has an enormous potential to restore the parenchymal tissue loss due to injury. This is accomplished by the proliferation of either the hepatocytes or liver progenitor cells in cases where massive damage prohibits hepatocytes from entering the proliferative response. Under debate is still whether hepatic stem cells are involved in liver tissue maintenance and regeneration or even whether they exist at all. The definition of an adult tissue‐resident stem cell comprises basic functional stem cell criteria like the potential of self‐renewal, multipotent, i.e. at least bipotent differentiation capacity and serial transplantability featuring the ability of functional tissue repopulation. The relationship between a progenitor and its progeny should exemplify the lineage commitment from the putative stem cell to the differentiated cell. This is mainly assessed by lineage tracing and immunohistochemical identification of markers specific to progenitors and their descendants. Flow cytometry approaches revealed that the liver stem cell population in animals is likely to be heterogeneous giving rise to progeny with different molecular signatures, depending on the stimulus to activate the putative stem cell compartment. The stem cell criteria are met by a variety of cells identified in the fetal and adult liver both under normal and injury conditions. It is the purpose of this review to verify hepatic stem cell candidates in the light of the stem cell definition criteria mentioned. Also from this point of view adult stem cells from non‐hepatic tissues such as bone marrow, umbilical cord blood or adipose tissue, have the potential to differentiate into cells featuring functional hepatocyte characteristics. This has great impact because it opens the possibility of generating hepatocyte‐like cells from adult stem cells in a sufficient amount and quality for their therapeutical application to treat end‐stage liver diseases by stem cell‐based hepatocytes in place of whole organ transplantation. © 2012 International Society for Advancement of Cytometry

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Human hepatocytes in mice receiving pre-immune injection with human cord blood cells

Cited by 24 publications

References 39 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

Phenotypic changes of human cells in human-rat liver during partial hepatectomy-induced regeneration

Implication of hepatic stem cells in functional liver repopulation

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