Formation of human hepatocytes by human hematopoietic stem cells in sheep

Almeida-Porada, Graça; Porada, Christopher D.; Chamberlain, Jason; Torabi, Alireza; Zanjani, Esmail D.

doi:10.1182/blood-2004-01-0259

Cited by 123 publications

(80 citation statements)

References 44 publications

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“…Nevertheless, bone marrow cell therapies in animal models and patients have produced some interesting results. For example, while bone marrow fails to contribute to liver development in neonatal mice [102], impressive numbers of hepatocytes appear to be human cord blood (CD34 − lin − ) -derived when the cord blood is transplanted in to either pre-immune fetal sheep [103] or goats [104]. In animal models, the most promising cells for therapy appear to be mesenchymal stem cells (MSCs).…”

Section: Bone Marrowmentioning

confidence: 99%

Stem cells in liver regeneration, fibrosis and cancer: the good, the bad and the ugly

Alison

Islam

Lim

2008

The Journal of Pathology

201

149

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The worldwide shortage of donor livers to transplant end stage liver disease patients has prompted the search for alternative cell therapies for intractable liver diseases, such as acute liver failure, cirrhosis and hepatocellular carcinoma (HCC). Under normal circumstances the liver undergoes a low rate of hepatocyte 'wear and tear' renewal, but can mount a brisk regenerative response to the acute loss of two-thirds or more of the parenchymal mass. A body of evidence favours placement of a stem cell niche in the periportal regions, although the identity of such stem cells in rodents and man is far from clear. In animal models of liver disease, adopting strategies to provide a selective advantage for transplanted hepatocytes has proved highly effective in repopulating recipient livers, but the poor success of today's hepatocyte transplants can be attributed to the lack of a clinically applicable procedure to force a similar repopulation of the human liver. The activation of bipotential hepatic progenitor cells (HPCs) is clearly vital for survival in many cases of acute liver failure, and the signals that promote such reactions are being elucidated. Bone marrow cells (BMCs) make, at best, a trivial contribution to hepatocyte replacement after damage, but other BMCs contribute to the hepatic collagen-producing cell population, resulting in fibrotic disease; paradoxically, BMC transplantation may help alleviate established fibrotic disease. HCC may have its origins in either hepatocytes or HPCs, and HCCs, like other solid tumours appear to be sustained by a minority population of cancer stem cells.

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Section: Bone Marrowmentioning

confidence: 99%

Stem cells in liver regeneration, fibrosis and cancer: the good, the bad and the ugly

Alison

Islam

Lim

2008

The Journal of Pathology

201

149

View full text Add to dashboard Cite

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“…However, it has been demonstrated by several groups that purified HSCs may differentiate into or fuse with several non-hematopoietic cell (HC) types. [4][5][6][7][8][9][10] The ectopic expression of hematopoietic genes in non-hematopoietic tissues raises safety concerns. Further improvements in vector design to achieve specific and efficient expression of transgenes in target tissues would increase the safety of the procedure and are therefore desirable.…”

Section: Introductionmentioning

confidence: 99%

Lentiviral vectors transcriptionally targeted to hematopoietic cells by WASP gene proximal promoter sequences

et al. 2005

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“…Furthermore, fusion as a major contributor to the observed donor-derived chimerism was excluded in several recently published elegant studies. [18][19][20][21][22][23][24] In the deliberations concerning stem cell plasticity, the concept that BM may contain heterogeneous populations of stem cells was surprisingly not taken carefully enough into consideration. To support this notion several studies from our and other laboratories provided direct evidence that BM stem cells are heterogenous and perhaps pluripotent.…”

Section: Introductionmentioning

confidence: 99%

A population of very small embryonic-like (VSEL) CXCR4+SSEA-1+Oct-4+ stem cells identified in adult bone marrow

et al. 2006

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By employing multiparameter sorting, we identified in murine bone marrow (BM) a homogenous population of rare (B0.02% of BMMNC) Sca-1 þ lin À CD45 À cells that express by RQ-PCR and immunohistochemistry markers of pluripotent stem cells (PSC) such as SSEA-1, Oct-4, Nanog and Rex-1. The direct electronmicroscopical analysis revealed that these cells are small (B2-4 lm), posses large nuclei surrounded by a narrow rim of cytoplasm, and contain open-type chromatin (euchromatin) that is typical for embryonic stem cells. In vitro cultures these cells are able to differentiate into all three germ-layer lineages. The number of these cells is highest in BM from young (B1-monthold) mice and decreases with age. It is also significantly diminished in short living DBA/2J mice as compared to long living B6 animals. These cells in vitro respond strongly to SDF-1, HGF/SF and LIF and express CXCR4, c-met and LIF-R, respectively, and since they adhere to fibroblasts they may be coisolated with BM adherent cells. We hypothesize that this population of Sca-1 þ lin À CD45 À very small embryonic-like (VSEL) stem cells is deposited early during development in BM and could be a source of pluripotent stem cells for tissue/ organ regeneration.

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Formation of human hepatocytes by human hematopoietic stem cells in sheep

Cited by 123 publications

References 44 publications

Stem cells in liver regeneration, fibrosis and cancer: the good, the bad and the ugly

Stem cells in liver regeneration, fibrosis and cancer: the good, the bad and the ugly

Lentiviral vectors transcriptionally targeted to hematopoietic cells by WASP gene proximal promoter sequences

A population of very small embryonic-like (VSEL) CXCR4+SSEA-1+Oct-4+ stem cells identified in adult bone marrow

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