Improved conditions to induce hepatocytes from rat bone marrow cells in culture

Miyazaki, Masahiro; Akiyama, Ichiro; Sakaguchi, Masakiyo; Nakashima, Emiko; Okada, Mayumi; Kataoka, Ken; Huh, Nam

doi:10.1016/s0006-291x(02)02340-9

Cited by 84 publications

(65 citation statements)

References 30 publications

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“…25 There is evidence for the presence of a common progenitor cell population of hematopoietic and mesenchymal stem cells. 26,27 Cells in normal bone marrow that expressed some differentiation marker proteins of muscle cells 28 or hepatocytes 29 have been found. Further extensive studies are needed, however, to gain clear insights into stem cell populations, their plasticity, and the interrelationships among them in bone marrow.…”

Section: Discussionmentioning

confidence: 99%

Participation of Adult Mouse Bone Marrow Cells in Reconstitution of Skin

Kataoka

Medina

Kageyama

et al. 2003

The American Journal of Pathology

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122

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Results of recent studies have indicated that bone marrow cells can differentiate into various cells of ectodermal, mesodermal, and endodermal origins when transplanted into the body. However, the problems associated with those experiments such as the long latent period, rareness of the event, and difficulty in controlling the processes have hampered detailed mechanistic studies. In the present study, we examined the potency of mouse bone marrow cells to differentiate into cells comprising skin tissues using a skin reconstitution assay. Bone marrow cells from adult green fluorescent protein (GFP)-transgenic mice were transplanted in a mixture of embryonic mouse skin cells (17.5 days post-coitus) onto skin defects made on the backs of nude mice. Within 3 weeks, fully differentiated skin with hair was reconstituted. GFP-positive cells were found in the epidermis, hair follicles, sebaceous glands, and dermis. The localization and morphology of the cells, results of immunohistochemistry, and results of specific staining confirmed that the bone marrow cells had differentiated into epidermal keratinocytes, sebaceous gland cells, follicular epithelial cells, dendritic cells, and endothelial cells under the present conditions. These results indicate that this system is suitable for molecular and cellular mechanistic studies on differentiation of stem cells to various epidermal and dermal cells.

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Section: Discussionmentioning

confidence: 99%

Participation of Adult Mouse Bone Marrow Cells in Reconstitution of Skin

Kataoka

Medina

Kageyama

et al. 2003

The American Journal of Pathology

Self Cite

122

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“…Studies have been undertaken mostly in rodents [7,9,[14][15][16][17], but in humans, bone marrow [8,[18][19][20], amniotic tissue [21], cord blood [22], and adult and fetal liver have been studied.…”

Section: Discussionmentioning

confidence: 99%

Epithelial Colonies Cultured from Human Explanted Liver in Subacute Hepatic Failure Exhibit Hepatocyte, Biliary Epithelial, and Stem Cell Phenotypic Markers

et al. 2003

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The liver in subacute hepatic failure may become enriched for hepatic progenitor cells. Liver tissue from such a patient was collagenase digested and, from the nonparenchymal cell fraction, epithelioid colonies were developed. Albumin and alpha-1-antitrypsin (AAT) were secreted for greater than 120 days from these colonies. Reverse transcription-polymerase chain reaction showed expression of markers of both hepatocyte and biliary epithelial phenotypes (cytokeratins 7, 18, and 19, albumin and AAT, hepatocyte growth factor receptor, transforming growth factor beta receptor type II, gamma-glutamyl transpeptidase, biliary glycoprotein). The cell cycle regulator p21 was also expressed. The POU domain transcription factor octamer-binding protein 4 was present in these cells, but not in RNA or cDNA prepared from adult human liver. These markers were maintained even after 165 days culture. Proliferating epithelial-like cells with combined hepatocyte-and biliary-epithelial-specific functional markers and a stem cell marker can be isolated from the nonparenchymal fraction of liver cells in subacute hepatic failure. Stem

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“…6,7,28 Potential candidates include hepatocyte growth factor, epidermal growth factor, oncostatin M, and vascular endothelial growth factor, and these factors were therefore nominated as modulators of stem cell differentiation. 5,[29][30][31] However, the length of time required during hepatic differentiation of MSCs under prolonged exposure in the specific culture media is the major drawback. On average, the expression of hepatic-specific genes in MSCs were detectable by culturing in growth factor-enriched medium for more than 1 week.…”

Section: Discussionmentioning

confidence: 99%

Activation of interleukin-6-induced glycoprotein 130/signal transducer and activator of transcription 3 pathway in mesenchymal stem cells enhances hepatic differentiation, proliferation, and liver regeneration

et al. 2010

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Adult bone marrow-derived mesenchymal stem cells (MSCs) exist in all living species and are capable of differentiating into different types of specific cells. In this study, we demonstrate the therapeutic effectiveness of rat MSC transplantation in D-galactosamine (GalN)-induced acute liver injury and identified the novel pathways which are involved in hepatic differentiation of MSCs. In vivo, intraportal transplantation with 5 Â 10 6 MSCs at 24 hours after GalN administration resulted in significant reduction in serum levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin compared to the control group. Engrafted MSCs actively proliferated, differentiated, and further enhanced hepatocyte proliferation activity. In vitro, coculture of MSCs with GalN-induced injured hepatocytes showed efficient differentiation and was evidenced by progressive increase in messenger RNA levels of hepatic markers, including albumin, a-fetoprotein, CCAAT-enhancer binding protein a, a-1-antitryspin, and hepatocyte nuclear factor-3b. Immunofluorescent staining revealed that these cells were positive for albumin, a-fetoprotein, and cytokeratin 18, but not clusters of differentiation 34, cytokeratin 19, or OV6. During hepatic differentiation, signal transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling were constantly activated, and a gradual down-regulation of b-catenin expression in messenger RNA and protein levels was detected. Hyper-interleukin-6 fusion protein but not interleukin-6 (IL-6) alone caused reduction in b-catenin expression associated with the up-regulation of Wnt-5a in MSCs via activating the glycoprotein 130 (gp130)-mediated STAT3 signaling pathway, which indicates the operation of the trans-signaling mechanism. Activation of IL-6/gp130-mediated STAT3 signaling pathway in MSCs triggered wound healing, cell migration, and proliferation. In conclusion, transplantation of MSCs promotes cell proliferation and organ repair, and activation of IL-6/gp130-mediated STAT3 signaling pathway via soluble IL-6 receptor is crucial in hepatic differentiation of MSCs. Liver Transpl 16:1195-1206. V C 2010 AASLD. Received February 19, 2010 accepted July 7, 2010. Additional Supporting Information may be found in the online version of this article.Abbreviations: AFP, a-fetoprotein; ALT, alanine aminotransferase; APC, adenomatous polyposis coli; AR, androgen receptor; AST, aspartate aminotransferase; CEBP, CCAAT/enhancer binding protein; CK, cytokeratin; CTNN b 1, b-catenin; DAPI, 4 0 ,6-diamidino-2-phenylindole; DVL1, dishevelled; ERK, extracellular signal-regulated kinase; FISH, fluorescent in situ hybridization; FITC, fluorescein isothiocyanate; DMEM, Dulbecco's modified Eagle medium; FBS, fetal bovine serum; GalN, D-galactosamine; GFP, green fluorescent protein; GSK3bglycoprotein synthase kinase 3b; IL, interleukin; IP, immunoprecipitation; MAPK, mitogenactivated protein kinase; mRNA, messenger RNA; MSC, mesenchy...

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Improved conditions to induce hepatocytes from rat bone marrow cells in culture

Cited by 84 publications

References 30 publications

Participation of Adult Mouse Bone Marrow Cells in Reconstitution of Skin

Participation of Adult Mouse Bone Marrow Cells in Reconstitution of Skin

Epithelial Colonies Cultured from Human Explanted Liver in Subacute Hepatic Failure Exhibit Hepatocyte, Biliary Epithelial, and Stem Cell Phenotypic Markers

Activation of interleukin-6-induced glycoprotein 130/signal transducer and activator of transcription 3 pathway in mesenchymal stem cells enhances hepatic differentiation, proliferation, and liver regeneration

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