Hepatocyte Growth Factor Induces Differentiation of Adult Rat Bone Marrow Cells into a Hepatocyte Lineage in Vitro

Anemia is a severe complication in patients with chronic kidney disease (CKD). Treatment with exogenous erythropoietin (EPO) can correct anemia in many with CKD. We produced 5/6-nephrectomized rats that became uremic and anemic at 25 days post surgery. Injection of the anemic 5/6-nephrectomized rats with 2.8 mg zinc/kg body weight raised their red blood cell (RBC) levels from approximately 85% of the control to 95% in one day and continued for 4 days. We compared the effect of ZnSO4 and recombinant human erythropoietin (rHuEPO) injections on relieving anemia in 5/6-nephrectomized rats. After three consecutive injections, both the ZnSO4 and rHuEPO groups had significantly higher RBC levels (98 ± 6% and 102 ± 6% of the control) than the saline group (90 ± 3% of the control). In vivo, zinc relieved anemia in 5/6-nephrectomized rats similar to rHuEPO. In vitro, we cultured rat bone marrow cells supplemented with ZnCl2, rHuEPO, or saline. In a 4-day suspension culture, we found that zinc induced erythropoiesis similar to rHuEPO. When rat bone marrow cells were supplement-cultured with zinc, we found that zinc stimulated the production of EPO in the culture medium and that the level of EPO produced was dependent on the concentration of zinc supplemented. The production of EPO via zinc supplementation was involved in the process of erythropoiesis.

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A comparative study on BMP-induced osteoclastogenesis and osteoblastogenesis in primary cultures of adult rat bone marrow cells

Growth Factors ◽

10.1080/08977190802707324 ◽

2009 ◽

Vol 27 (2) ◽

pp. 121-131 ◽

Cited By ~ 22

Author(s):

Sangita Paul ◽

John C. Lee ◽

Lee-Chuan C. Yeh

Keyword(s):

Bone Marrow ◽

Comparative Study ◽

Bone Marrow Cells ◽

Primary Cultures ◽

Adult Rat ◽

Rat Bone ◽

Marrow Cells

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Effect of Normal and Neutropenic Dog Sera on Nucleic Acids of Rat Bone Marrow Cells in vitro*

Journal of Veterinary Medicine Series A ◽

10.1111/j.1439-0442.1986.tb00516.x ◽

1986 ◽

Vol 33 (1-10) ◽

pp. 123-130 ◽

Cited By ~ 1

Author(s):

G. A. Montes ◽

A. S. Islas ◽

E. Ocharan ◽

J. A. Correa ◽

W. G. Rudolph

Keyword(s):

Bone Marrow ◽

Nucleic Acids ◽

Bone Marrow Cells ◽

Rat Bone ◽

Marrow Cells

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Erythropoietin induces production of hepatocyte growth factor from bone marrow mesenchymal stem cells in vitro

Biologicals ◽

10.1016/j.biologicals.2016.10.010 ◽

2017 ◽

Vol 45 ◽

pp. 15-19 ◽

Cited By ~ 4

Author(s):

Kaveh Tari ◽

Amir Atashi ◽

Saied Kaviani ◽

Mahshid AkhavanRahnama ◽

Azadeh Anbarlou ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Growth Factor ◽

Hepatocyte Growth Factor ◽

Marrow Mesenchymal Stem Cells ◽

Hepatocyte Growth

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ФЕНОТИПОВІ ТА МОРФОЛОГІЧНІ ЗМІНИ КУЛЬТУРИ КЛІТИН КІСТКОВОГО МОЗКУ ЩУРІВ В ПРОЦЕСІ ЇХ КУЛЬТИВУВАННЯ

Scientific Messenger of LNU of Veterinary Medicine and Biotechnology ◽

10.15421/nvlvet6626 ◽

2016 ◽

Vol 18 (2(66)) ◽

pp. 126-132

Author(s):

A.I. Mazurkiewicz ◽

V.V. Kovpak ◽

O.S. Kovpak

Keyword(s):

Stem Cells ◽

Cell Culture ◽

Bone Marrow ◽

Bone Marrow Cells ◽

Morphological Changes ◽

Embryonic Stem ◽

In Vitro Cultivation ◽

Rat Bone ◽

Marrow Cells

Bone marrow is the only adult tissue which normally consists of immature undifferentiated and low differentiated cells which called stem cells and they are similar in structure to embryonic stem cells. But literature data analysis doesn't give an unambiguous answer regarding phenotypic and morphological changes of bone marrow cells culture of rats during their in vitro cultivation which necessitated further research.Investigate phenotypic and morphological changes of bone marrow cells culture of rats during their in vitro cultivation from first to fourth passage.We were used in these research bone marrow cells of rats from the first to the fourth passages. Microscopic analysis and evaluation morphological changes of bone marrow cells culture of rats during cultivation were carried out using inverted microscope Axiovert 40. Control of changes phenotype was performed by detecting CD markers (CD10, CD38, CD34, CD45, CD48, CD54, CD56, CD66e, CD96, CD227, CD326, pan–keratin). The evaluation was performed by the semi– quantitative method (H–Score).The research of primary culture of rat bone marrow cells showed that it morphologically heterogeneous, noted the small number of cells polygonal shape, surrounded by the fibroblast cells. During the cultivation cell culture becomes more homogenous at the expense of fibroblast–like cells. As a result of occurred the transition process from heterogeneous culture in zero passage to the most homogeneous culture in 4 passage. Immunophenotyping population of cell culture derived from rat bone marrow, revealed a high level of expression of pan–keratin; moderate level – CD34, CD48, CD66e, CD95; low level – CD38, CD45, CD56, CD227, CD326; lack of expression – CD10, CD54. Change of the expression of surface markers varies in each passage CD48, CD66e, CD95 increased significantly; CD38, SD45, SD326, pan–keratin reduced significantly. The markers CD34, CD 56, CD 227 were expressed on the one level from the first to the fourth passage. The expression of the CD10, CD54 markers during the study period was not identified.

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Zebularine Promotes Hepatic Differentiation of Rabbit Bone Marrow Mesenchymal Stem Cells by Interfering with p38 MAPK Signaling

Stem Cells International ◽

10.1155/2018/9612512 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Yong-Heng Luo ◽

Juan Chen ◽

En-Hua Xiao ◽

Qiu-Yun Li ◽

Yong-Mei Luo

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Growth Factor ◽

Hepatocyte Growth Factor ◽

Hepatic Differentiation ◽

Urea Production ◽

Marrow Mesenchymal Stem Cells ◽

Hepatocyte Growth

Demethylating agent zebularine is reported to be capable of inducing differentiation of stem cells by activation of methylated genes, though its function in hepatocyte differentiation is unclear. p38 signal pathway is involved in differentiation of hepatocytes and regulating of DNA methyltransferases 1 (DNMT1) expression. However, little is known about the impact of zebularine on bone marrow mesenchymal stem cells (BMMSCs) and p38 signaling during hepatic differentiation. The present study investigated the effects of zebularine on hepatic differentiation of rabbit BMMSCs, as well as the role of p38 on DNMT1 and hepatic differentiation, with the aim of developing a novel strategy for improving derivation of hepatocytes. BMMSCs were treated with zebularine at concentrations of 10, 20, 50, and 100 μM in the presence of hepatocyte growth factor; changes in the levels of hepatic-specific alpha-fetoprotein and albumin were detected and determined by RT-PCR, WB, and immunofluorescence staining. Expression of DNMT1 and phosphorylated p38 as well as urea production and ICG metabolism was also analyzed. Zebularine at concentrations of 10, 20, and 50 μM could not affect cell viability after 48 h. Zebularine treatment leads to an inhibition of DNMT activity and increase of hepatic-specific proteins alpha-fetoprotein and albumin in BMMSCs in vitro; zebularine addition also induced expression of urea production of and ICG metabolism. p38 signal was activated in BMMSCs simulated with HGF; inhibition of p38 facilitated the synthesis of DNMT1 and albumin in cells. Zebularine restrained DNMT1 and phosphorylated p38 which were induced by HGF. Therefore, this study demonstrated that treatment with zebularine exhibited terminal hepatic differentiation of BMMSCs in vitro in association with hepatocyte growth factor; p38 pathway at least partially participates in zebularine-induced hepatic differentiation of rabbit BMMSCs.

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