Downregulation of β2-microglobulin in human cord blood somatic stem cells after transplantation into livers of SCID-mice: an escape mechanism of stem cells?

Beerheide, Walter; Mach, M.-A. von; Ringel, Michael; Fleckenstein, Corinna; Schumann, Susanne; Renzing, N.; Hildebrandt, Andreas; Brenner, Walburgis; Jensen, Oliver E.; Gebhard, Susanne; Reifenberg, Kurt; Bender, Jörg; Oesch, Franz; Hengstler, Jan G.

doi:10.1016/s0006-291x(02)00596-x

Cited by 42 publications

(23 citation statements)

References 46 publications

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“…Embryonic stem cells were also shown to differentiate into hepatocytes (Hamazaki et al, 2001). In humans, embryonic stem cells (Rambhatla et al, 2003), bone marrow-derived cells (Danet et al, 2002), and cord blood cells (Beerheide et al, 2002;Danet et al, 2002;Kakinuma et al, 2003) have been shown to be possible candidate cell sources for hepatocyte transplantation.…”

Section: Introductionmentioning

confidence: 99%

Human Amniotic Epithelial Cells Possess Hepatocyte-like Characteristics and Functions

Takashima

Ise

Zhao

et al. 2004

Cell Struct. Funct.

134

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ABSTRACT. Hepatocyte transplantation is expected to become a novel method for treatment of liver disease. However, many questions remain regarding this approach, especially concerning donor cells. To evaluate whether human amniotic epithelial cells can be used as a cell source for hepatocyte transplantation, hepatic gene expression and functions of human amniotic epithelial cells were analyzed. Reverse transcription-polymerase chain reaction analysis demonstrated that human amniotic epithelial cells expressed albumin, α1-antitrypsin, and other hepatocyte-related genes. Cultivated human amniotic epithelial cells demonstrated albumin production, glycogen storage, and albumin secretion consistent with the hepatocyte gene expression profile. In organ culture, the amnion secreted 30-fold larger amounts of albumin than human amniotic epithelial cells in monolayer culture. Moreover, in organ culture the amnion also secreted α1-antitrypsin. Following transplantation into mice, the amnion survived and secreted albumin. These observations suggest that transplantation of human amniotic epithelial cells and/or amnion could be novel therapeutic strategy for treatment of hepatic diseases, including α1-antitrypsin deficiency.

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Section: Introductionmentioning

confidence: 99%

Human Amniotic Epithelial Cells Possess Hepatocyte-like Characteristics and Functions

Takashima

Ise

Zhao

et al. 2004

Cell Struct. Funct.

134

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“…Ishikawa et al 26 detected human albumin and the HepPar1 antigen in livers of immunodeficient mice, postulating that the engrafted cells from human cord blood "functioned as hepatocytes." However, other scientists 10,13,27,28 (for a review, see Hengstler et al 1 ), including our group, remained skeptical because we observed the expression of some but not all hepatocyte markers that should be expressed by a real human hepatocyte. Because of its high relevance, we decided to study more closely the fate of human stem cells in mouse livers.…”

Section: Discussionmentioning

confidence: 73%

“…The isolation of human adherently proliferating cord blood cells, 10 human monocyte-derived NeoHep cells, 11 nestin-positive hepatopancreatic precursor cells, 12,13 mesenchymal bone marrow cells, 14 and primary human hepatocytes 15 was performed as described (for a detailed description, see the supplementary material). Marking with CM-DiI was performed with a commercially available kit (Invitrogen, Karlsruhe, Germany).…”

Section: Methodsmentioning

confidence: 99%

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Fate of extrahepatic human stem and precursor cells after transplantation into mouse livers

et al. 2007

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“…For instance, analysis of the metastatic properties of human tumor cells in mice demands a clear-cut diVerentiation between the human and the host's cells (Voura et al 2004;Chambers et al 2002;Fidler 2003;Friedl and Wolf 2003;Hengstler et al 2006;Schmidt et al 2007;Tanner et al 2006;Hausherr et al 2006;Spangenberg et al 2006). Recently, numerous groups have analyzed the fate and diVerentiation capacity of human stem cells after transplantation into mice Aurich et al 2007;Eberhardt et al 2006;Ruhnke et al 2005a, b;Beerheide et al 2002). These studies usually aim at demonstrating that previously silent markers of diVerentiated cells become expressed in the transplanted stem cells.…”

Section: Introductionmentioning

confidence: 99%

Tracking of human cells in mice

Schormann

Hammersen

Brulport

et al. 2008

Histochem Cell Biol

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Tracking and tracing of transplanted cells in mice is required in many fields of research. Examples are transplantation of stem cells into organs of mice to study their differentiation capacity and injection of tumor cells to examine metastatic behavior. In the present study we tested the lipid dye CM-DiI and red fluorescent nanoparticles Qdot655 for their applicability in tagging and tracing of human cells in mice. Labeling of different cell types, including MCF-7 human breast cancer cells, human cord blood derived cells, human NeoHep cells and human hepatopancreatic precursor cells, is technically easy and did not compromise further cell culture. After transplantation of CM-DiI or Qdot655 marked cells, red fluorescent structures could be detected already in unprocessed paraffin slices of the studied organs, namely liver, lung, pancreas, kidney, spleen and bone marrow. Next, we examined whether the red fluorescent structures represent the transplanted human cells. For this purpose, we established an in situ hybridization (ISH) technique that allows clear-cut differentiation between human and murine nuclei, based on simultaneous hybridization with human alu and mouse major satellite (mms) probes. We observed a high degree of coincidence between CM-DiI-marked cells and alu positive nuclei. However, also some mms positive cells contained CM-DiI, suggesting phagocytosis of the transplanted CM-DiI-marked cells. The degree of such CM-DiI-positive mouse cells depended on the cell type and route of administration. From a technical point of view it was important that CM-DiI-positive structures in paraffin slices remained fluorescent also after ISH. In contrast, Qdot655 positive structures faded during further staining procedures. In conclusion, marking of cells with CM-DiI or Qdot655 prior to transplantation facilitates recovery of human cells, since a high fraction of positive structures in the host's tissue originate from the transplanted cells. However, CM-DiI or Qdot655 positive staining of individual cells in transplanted tissues is not sufficient to prove their human origin. Additional procedures, such as ISH with alu-probes, are essential, when characterizing individual cells.

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Downregulation of β2-microglobulin in human cord blood somatic stem cells after transplantation into livers of SCID-mice: an escape mechanism of stem cells?

Cited by 42 publications

References 46 publications

Human Amniotic Epithelial Cells Possess Hepatocyte-like Characteristics and Functions

Human Amniotic Epithelial Cells Possess Hepatocyte-like Characteristics and Functions

Fate of extrahepatic human stem and precursor cells after transplantation into mouse livers

Tracking of human cells in mice

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