Differentiation of bone marrow cells into cells that express liver-specific genes in vitro: implication of the Notch signals in differentiation

Okumoto, Kazuo; Saito, Takafumi; Hattori, Etsuko; Ito, Junitsu; Adachi, Tsuyoshi; Terada, Tadashi; Sugahara, Kazuhiko; Watanabe, Hisayoshi; Saito, Koji; Togashi, Hitoshi; Kawata, Satoshi

doi:10.1016/s0006-291x(03)00637-5

Cited by 68 publications

(69 citation statements)

References 17 publications

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“…Subsequent PCR was performed in 100-l reaction mixture containing 1ϫ PCR buffer, 2 mM MgCl 2 , 2.5 units of TaqDNA polymerase, 1 l of cDNA, and 150 nM specific sets of primers. The primer sequence and cycling condition for CYP2C11 (Zaphiropoulos and Wood, 1993) and glyceraldehyde-3-phosphate dehydrogenase (Okumoto et al, 2003) were reported elsewhere. PCR was performed in a GeneAmp PCR System 9600 thermocycler (PerkinElmer Life and Analytical Sciences, Boston, MA).…”

Section: Methodsmentioning

confidence: 99%

Inadequacy of the Janus Kinase 2/Signal Transducer and Activator of Transcription Signal Transduction Pathway to Mediate Episodic Growth Hormone-Dependent Regulation of Hepatic CYP2C11

Verma

Dhir²,

Shapiro³

2004

Mol Pharmacol

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CYP2C11, the most commonly expressed hepatic cytochrome P450 isoform in male rats, is induced by the masculine "episodic" secretory growth hormone profile. A considerable number of reports have indicated that episodic growth hormone effects are mediated by the activation of the Janus kinase 2 (Jak2)/signal transducer and activator of transcription (Stat)5B signal transduction pathway. We observed that restoration of the normal masculine plasma growth hormone pulse in hypophysectomized male rats did indeed rapidly activate (phosphorylate) Jak2, shortly followed by activation and nuclear translocation of Stat5B. Infusion of a growth hormone pulse with an amplitude that was 10% of the normal height induced a dramatic overexpression of CYP2C11, had little effect activating Jak2, but induced a more rapid and greater accumulation of activated nuclear Stat5B. Restoration of a growth hormone pulse with an amplitude of only 1% of normal had little effect phosphorylating Jak2, activated and translocated to the hepatic nucleus ϳ70% of the normally induced levels of Stat5B, but had no inductive effect on CYP2C11. Last, the hypophysectomized male rat receiving no growth hormone replacement expressed 25 to 35% of normal concentrations of CYP2C11 despite no measurable activation of either Jak2 or Stat5B. These results raise concerns regarding the requisite role of the Jak2/Stat5B pathway in mediating episodic growth hormone regulation of CYP2C11. However, accumulation of activated extracellular signal-regulated kinase (ERK)1 and ERK2 were the only transducers measured in the study not affected by the 1% replacement pulse of growth hormone and were elevated 2-to 3-fold above normal when the pulse was renaturalized to 10% of physiological amplitude, suggesting the possible involvement of mitogen-activated protein kinase in episodic growth hormone regulation of CYP2C11.

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Section: Methodsmentioning

confidence: 99%

Inadequacy of the Janus Kinase 2/Signal Transducer and Activator of Transcription Signal Transduction Pathway to Mediate Episodic Growth Hormone-Dependent Regulation of Hepatic CYP2C11

Verma

Dhir²,

Shapiro³

2004

Mol Pharmacol

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“…Sca-1ϩ Cells Can Differentiate into Osteocytes and Adipocytes-It has been reported that Sca-1ϩ cells from skeletal muscle and bone marrow differentiate into various types of cells such as adipocytes, endothelial cells, muscle, neural, and hepatic cells (9,11,14). To determine whether the Sca-1ϩ cells from the adult murine heart have pluripotency, we examined whether these cells could differentiate into cells other than cardiomyocytes.…”

Section: Cell Surface Antigens Of Sca-1ϩ Cells Derived From the Adultmentioning

confidence: 99%

“…Recently many reports have demonstrated that multipotential stem cells derived from bone marrow and skeletal muscle express Sca-1. Okumoto et al (9) have reported that Sca-1ϩ cells from bone marrow differentiate into hepatocyte when treated with hepatic growth factor. Gojo et al (10) have reported that adult mesenchymal stem cells from bone marrow abundantly express Sca-1 and differentiate into cardiomyocyte in vivo.…”

mentioning

confidence: 99%

Adult Cardiac Sca-1-positive Cells Differentiate into Beating Cardiomyocytes

Matsuura

Nagai

Nishigaki

et al. 2004

Journal of Biological Chemistry

597

369

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Although somatic stem cells have been reported to exist in various adult organs, there have been few reports concerning stem cells in the heart. We here demonstrate that Sca-1-positive (Sca-1؉) cells in adult hearts have some of the features of stem cells. Sca-1؉ cells were isolated from adult murine hearts by a magnetic cell sorting system and cultured on gelatin-coated dishes. A fraction of Sca-1؉ cells stuck to the culture dish and proliferated slowly. When treated with oxytocin, Sca-1؉ cells expressed genes of cardiac transcription factors and contractile proteins and showed sarcomeric structure and spontaneous beating. Isoproterenol treatment increased the beating rate, which was accompanied by the intracellular Ca 2؉ transients. The cardiac Sca-1؉ cells expressed oxytocin receptor mRNA, and the expression was up-regulated after oxytocin treatment. Some of the Sca-1؉ cells expressed alkaline phosphatase after osteogenic induction and were stained with OilRed O after adipogenic induction. These results suggest that Sca-1؉ cells in the adult murine heart have potential as stem cells and may contribute to the regeneration of injured hearts.

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“…However, the characteristic surface markers of BDLSCs and their pedigrees in the derivation of bone marrow stem cells remain obscure [7] . It is difficult to identify and sort particular cells by immunological methods, such as fluorescence-activated and magnetic-activated cell sorting [8,9] . Furthermore, the sorting of stem cells with complicated surface markers is difficult [10] .…”

Section: Function Tests Of Differentiated Cellsmentioning

confidence: 99%

Passage of bone-marrow-derived liver stem cells in a proliferating culture system

Cai¹,

Chen²,

Su³

et al. 2009

WJG

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AIM:To explore the feasibility of passage of bonemarrow-derived liver stem cells (BDLSCs) in culture systems that contain cholestatic serum. METHODS:Whole bone marrow cells of rats were purified with conditioning selection media that contained 50 mL/L cholestatic serum. The selected BDLSCs were grown in a proliferating culture system and a differentiating culture system. The culture systems contained factors that stimulated the proliferation and differentiation of BDLSCs. Each passage of the proliferated stem cells was subjected to flow cytometry to detect stem cell markers. The morphology and phenotypic markers of BDLSCs were characterized using immunohistochemistry, reverse transcription polymerase chain reaction (RT-PCR) and electron microscopy. The metabolic functions of differentiated cells were also determined by glycogen staining and urea assay. RESULTS:The conditioning selection medium isolated BDLSCs directly from cultured bone marrow cells. The selected BDLSCs could be proliferated for six passages and maintained stable markers in our proliferating system. When the culture system was changed to a differentiating system, hepatocyte-like colony-forming units (H-CFUs) were formed. H-CFUs expressed markers of embryonic hepatocytes (alpha-fetoprotein, albumin and cytokeratin 8/18), biliary cells (cytokeratin 19), hepatocyte functional proteins (transthyretin and cytochrome P450-2b1), and hepatocyte nuclear factors 1α and -3β). They also had glycogen storage and urea synthesis functions, two of the critical features of hepatocytes. CONCLUSION:BDLSCs can be selected directly from bone marrow cells, and pure BDLSCs can be proliferated for six passages. The differentiated cells have hepatocyte-like phenotypes and functions. B D L S C s re p re s e n t a n e w m e t h o d t o p rov i d e a readily available alternate source of cells for clinical hepatocyte therapy.

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Differentiation of bone marrow cells into cells that express liver-specific genes in vitro: implication of the Notch signals in differentiation

Cited by 68 publications

References 17 publications

Inadequacy of the Janus Kinase 2/Signal Transducer and Activator of Transcription Signal Transduction Pathway to Mediate Episodic Growth Hormone-Dependent Regulation of Hepatic CYP2C11

Inadequacy of the Janus Kinase 2/Signal Transducer and Activator of Transcription Signal Transduction Pathway to Mediate Episodic Growth Hormone-Dependent Regulation of Hepatic CYP2C11

Adult Cardiac Sca-1-positive Cells Differentiate into Beating Cardiomyocytes

Passage of bone-marrow-derived liver stem cells in a proliferating culture system

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