Anti-fibrotic effect of chorionic plate-derived mesenchymal stem cells isolated from human placenta in a rat model of CCl4-injured liver: Potential application to the treatment of hepatic diseases

In cholestatic liver diseases, impaired bile excretion disrupts lipid homeostasis. We investigated changes of lipid metabolism, including mitochondrial β-oxidation, in a rat model of bile duct ligation (BDL) in which chorionic plate-derived mesenchymal stem cells (CP-MSCs) were transplanted. Serum cholesterol level, which was elevated after BDL, was significantly decreased following CP-MSC transplantation. The expression levels of genes involved in intracellular lipid uptake, including long-chain fatty acyl-CoA synthetases and fatty acid transport proteins, were decreased in rats after BDL; however, they were not significantly changed by subsequent CP-MSC transplantation. Carnitine palmitoyltransferase 1A (CPT1A), a rate-limiting enzyme in mitochondrial β-oxidation, was upregulated after BDL and then was downregulated after CP-MSC transplantation. CPT1A expression was changed via microRNA-33—a posttranscriptional regulator of CPT1A—in a peroxisome proliferator-activated receptor α-independent manner. Cellular adenosine triphosphate production—an indicator of mitochondrial function—was reduced after BDL and was restored by CP-MSC transplantation. Expression levels of heme oxygenases also were significantly affected following BDL and CP-MSC transplantation. Lipid metabolism is altered in response to chronic cholestatic liver injury and can be restored by CP-MSC transplantation. Our study findings support the therapeutic potential of CP-MSCs in cholestatic liver diseases and help in understanding the fundamental mechanisms by which CP-MSCs affect energy metabolism.

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Human placenta-derived mesenchymal stem cells trigger repair system in TAA-injured rat model via antioxidant effect

Aging ◽

10.18632/aging.202348 ◽

2020 ◽

Author(s):

Jeeyoon Na ◽

Joseph Song ◽

Hyun Ho Kim ◽

Jin Seok ◽

Jae Yeon Kim ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Rat Model ◽

Human Placenta ◽

Antioxidant Effect ◽

Repair System

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Combination Therapy of Placenta-Derived Mesenchymal Stem Cells with WKYMVm Promotes Hepatic Function in a Rat Model with Hepatic Disease via Vascular Remodeling

Cells ◽

10.3390/cells11020232 ◽

2022 ◽

Vol 11 (2) ◽

pp. 232

Author(s):

Ji Hye Jun ◽

Sohae Park ◽

Jae Yeon Kim ◽

Ja-Yun Lim ◽

Gyu Tae Park ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Combination Therapy ◽

Rat Model ◽

Vascular Remodeling ◽

Hepatic Function ◽

Hepatic Regeneration ◽

Primary Role ◽

Efficient Treatment ◽

Hepatic Diseases

Changes in the structure and function of blood vessels are important factors that play a primary role in regeneration of injured organs. WKYMVm has been reported as a therapeutic factor that promotes the migration and proliferation of angiogenic cells. Additionally, we previously demonstrated that placenta-derived mesenchymal stem cells (PD-MSCs) induce hepatic regeneration in hepatic failure via antifibrotic effects. Therefore, our objectives were to analyze the combination effect of PD-MSCs and WKYMVm in a rat model with bile duct ligation (BDL) and evaluate their therapeutic mechanism. To analyze the anti-fibrotic and angiogenic effects on liver regeneration, it was analyzed using ELISA, qRT-PCR, Western blot, immunofluorescence, and immunohistochemistry. Collagen accumulation was significantly decreased in PD-MSCs with the WKYMVm combination (Tx+WK) group compared with the nontransplantation (NTx) and PD-MSC-transplanted (Tx) group (p < 0.05). Furthermore, the combination of PD-MSCs with WKYMVm significantly promoted hepatic function by increasing hepatocyte proliferation and albumin as well as angiogenesis by activated FPR2 signaling (p < 0.05). The combination therapy of PD-MSCs with WKYMVm could be an efficient treatment in hepatic diseases via vascular remodeling. Therefore, the combination therapy of PD-MSCs with WKYMVm could be a new therapeutic strategy in degenerative medicine.

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Human chorionic-plate-derived mesenchymal stem cells restore hepatic lipid metabolism in a rat model of bile duct ligation

Journal of Hepatology ◽

10.1016/s0168-8278(18)31162-0 ◽

2018 ◽

Vol 68 ◽

pp. S459

Author(s):

Y.B. Lee ◽

J.H. Choi ◽

E.N. Kim ◽

J. Seok ◽

H.-J. Lee ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Lipid Metabolism ◽

Bile Duct ◽

Rat Model ◽

Bile Duct Ligation ◽

Hepatic Lipid Metabolism ◽

Hepatic Lipid ◽

Duct Ligation ◽

Chorionic Plate

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Autologous transplantation of mesenchymal stem cells into the portal vein of the miniature pig; a preliminary experiment for NOTES approach

Perspectives in Surgery ◽

10.33699/pis.2019.98.9.350-355 ◽

2019 ◽

Vol 98 (9) ◽

pp. 350-355

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cell Therapy ◽

Portal Vein ◽

Liver Parenchyma ◽

Miniature Pig ◽

Hepatic Diseases ◽

Study Results

Introduction: There is evidence that mesenchymal stem cells (MSCs) could trans-differentiate into the liver cells in vitro and in vivo and thus may be used as an unfailing source for stem cell therapy of liver disease. Combination of MSCs (with or without their differentiation in vitro) and minimally invasive procedures as laparoscopy or Natural Orifice Transluminal Endoscopic Surgery (NOTES) represents a chance for many patients waiting for liver transplantation in vain. Methods: Over 30 millions of autologous MSCs at passage 3 were transplanted via the portal vein in an eight months old miniature pig. The deposition of transplanted cells in liver parenchyma was evaluated histologically and the trans-differential potential of CM-DiI labeled cells was assessed by expression of pig albumin using immunofluorescence. Results: Three weeks after transplantation we detected the labeled cells (solitary, small clusters) in all 10 samples (2 samples from each lobe) but no diffuse distribution in the samples. The localization of CM-DiI+ cells was predominantly observed around the portal triads. We also detected the localization of albumin signal in CM-DiI labeled cells. Conclusion: The study results showed that the autologous MSCs (without additional hepatic differentiation in vitro) transplantation through the portal vein led to successful infiltration of intact miniature pig liver parenchyma with detectable in vivo trans-differentiation. NOTES as well as other newly developed surgical approaches in combination with cell therapy seem to be very promising for the treatment of hepatic diseases in near future.

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