scholarly journals Identification of the small molecule compound which induces hepatic differentiation of human mesenchymal stem cells

2015 ◽  
Vol 2 ◽  
pp. 32-41 ◽  
Author(s):  
Noriko Itaba ◽  
Tomohiko Sakabe ◽  
Keita Kanki ◽  
Junya Azumi ◽  
Hiroki Shimizu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Small Molecule ◽  
Human Mesenchymal Stem Cells ◽  
Hepatic Differentiation ◽  
Small Molecule Compound

Expression of HLA-G1 and G5 Enables Human Mesenchymal Stem Cells To Engraft at High Levels across Xenogeneic Barriers Following Transplantation into Immunocompetent Recipients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1195-1195 ◽  
Author(s):  
Takashi Yamagami ◽  
Chad Sanada ◽  
Heinz Wiendl ◽  
Esmail D. Zanjani ◽  
Christopher D. Porada ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune System ◽  
Cytotoxic T Cells ◽  
Human Lymphocytes ◽  
Human Mesenchymal Stem Cells ◽  
Hepatic Differentiation ◽  
Fetal Sheep ◽  
Time Points ◽  
Donor Cells

Abstract Although mesenchymal stem cells (MSC) have been shown to be fairly non-immunogenic, recent studies demonstrated that MSC are capable of activating and becoming targets of NK-mediated lysis. Furthermore, the ability of IFN-γ to induce MSC expression of HLA-II molecules shows that MSC are not completely immuno-inert. Expression of HLA-G has been associated with the maintenance of fetomaternal tolerance during pregnancy through its inhibition of the cytolytic functions of NK and cytotoxic T cells and of dendritic cell maturation. Here we investigated whether transduction of human MSC with a retroviral vector encoding HLA-G1 (MSC-G1) or G5 (MSC-G5) would render these cells and their differentiated progeny undetectable by the recipient’s immune system, and thereby allow us to efficiently transplant these cells into immuno-competent xenogeneic recipients. First, we performed mixed lymphocyte reactions using unmodified MSC (unMSC), MSC-G1 or MSC-G5 as stimulators, and lymphocytes from allogeneic human or sheep donors as responders. While neither unMSC nor MSC-G1 or -G5 elicited a significant proliferative response from human lymphocytes, sheep lymphocytes proliferated 2-6 fold more when cultured with unMSC than with MSC-G1 or MSC-G5. Next, we tested whether HLA-G1 and HLA-G5 expression would enable the engraftment of human MSC in fetal sheep later in gestation when donor cells are normally rejected due to the presence of a competent immune system. To this end, 105 unMSC, MSC-G1, or MSC-G5 were transplanted (Tx) into fetal sheep recipients during the pre-immune period (55 days; n=9), or after immunocompetence was achieved, at 82 days (n=10) or 104 days (n=8) of gestation. Evaluation of the recipients’ hematopoietic system at 42 days post-transplant for the presence of human cell engraftment, using a panel of antibodies specific to human blood cells, revealed that Tx at 55 days resulted in similar levels of engraftment for all cell types (MSC:4±0.9; MSC-G1:6±0.3; MSC-G5:5±0.3%). In contrast, while unMSC engrafted at very low levels at 82d and 104d, Tx of MSC-G1 and-G5 at these later time points not only overcame the immune barriers, but resulted in levels of engraftment that were considerably higher than those achieved during the pre-immune period (82d:7±1;18±2.% and 104d:12±2;16±2%). A similar outcome was seen with liver engraftment and hepatic differentiation with MSG-1 and -G5 giving rise to 3–5 times more hepatocytes than unMSC at later time points. However, even at the early Tx time point of 55days, MSC-G1 and -G5 gave rise to, respectively, 5 times and 2 times more donor-derived hepatocytes than their unMSC counterpart. Our studies demonstrate that the forced expression of HLA-G1 or G5 enables MSC to evade a competent recipient immune system and engraft at significant levels at times in gestation when donor cells are normally rejected. These studies may allow the broadening of the use of MSC to diseases in which an underlying MSC defect precludes the use of the patient’s own MSC.

Membrane bioreactor to guide hepatic differentiation of human mesenchymal stem cells

2018 ◽  
Vol 564 ◽  
pp. 832-841 ◽  
Author(s):  
Antonella Piscioneri ◽  
Haysam Mohamed Magdy Ahmed ◽  
Sabrina Morelli ◽  
Shervin Khakpour ◽  
Lidetta Giorno ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Membrane Bioreactor ◽  
Human Mesenchymal Stem Cells ◽  
Hepatic Differentiation

scholarly journals Ultrasensitive in Vivo Fluorescence Imaging of Mesenchymal Stem Cells and Small Molecule-Induced Pluripotent Stem Cells in BALB/c mice.

2021 ◽  
Author(s):  
Sang Yeon Lee ◽  
Ho-Seong Han ◽  
Sang Tae Kim ◽  
Tae Hyun Kim ◽  
Kye Ho Lee
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Injection Site ◽  
Small Molecule ◽  
Pluripotent Stem Cells ◽  
Clinical Studies ◽  
Human Mesenchymal Stem Cells ◽  
Multipotent Stem Cells ◽  
The Brain

Abstract BackgroundMesenchymal cell has been frequently used in clinical studies. Mesenchymal stem cells (MSCs) are self-renewing, multipotent stem cells with the potential to differentiate into multiple mesoderm lineages. But MSC have limitation in clinical application for treating human diseases because they can differentiate several types of cell but not all types. PSL (Pluripotent Stem cell Like cell) are newly developed pluripotent stem cells from human mesenchymal stem cells (hMSC) induced by small molecule compounds. These cells have potential advantages for clinical cell treatment compared with ESCs and iPSCs.MethodsWe induced pluripotency from MSC using small molecules. It has tried to trace MSC and PSL in mice using bioluminescent techniques, which can detect visible light emitted from cells labeled with miRNA conjugated fluorescent molecules. ResultsMSCs predominantly migrate into the brain and testis. They also migrate to the liver, omentum, mesentery, kidneys and spleen. Migration of PSL is similar to MSCs, in that they go to the brain, testis and other intraperitoneal organs. Fluorescent images of explanted organs show that the intensity of brain images is higher in the PSL mouse group than the MSC mouse group. However, testis, image intensity is higher in MSC mouse group than the PSL mouse group. In PSL but not MSC mice, fluorescence persisted at the injection site in the tail.ConclusionsIn this study, injected MSCs and PSL predominantly migrated to the brain and testis. But, PSL migration was more than MSC migration in Brain. Both cell types had a similar migration pattern except for persistent fluorescence at injection site in the tail vein of PSL mice. We expect these cell therapy may have many potentials for clinical studies on these notable treatments.

In vitro hepatic differentiation of human mesenchymal stem cells

Hepatology ◽  
2004 ◽  
Vol 40 (6) ◽  
pp. 1275-1284 ◽  
Author(s):  
Kuan-Der Lee ◽  
Tom Kwang-Chun Kuo ◽  
Jacqueline Whang-Peng ◽  
Yu-Fen Chung ◽  
Ching-Tai Lin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Hepatic Differentiation

Hepatic Differentiation of Rat Mesenchymal Stem Cells by a Small Molecule

ChemMedChem ◽  
2012 ◽  
Vol 7 (8) ◽  
pp. 1447-1452 ◽  
Author(s):  
Jingfeng Ouyang ◽  
Jiaan Shao ◽  
Hongbin Zou ◽  
Yijia Lou ◽  
Yongping Yu
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Small Molecule ◽  
Hepatic Differentiation
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