Wnt Pathway Activation by Placental Mesenchymal Stem Cells Promotes Hepatic Regeneration in a Cirrhotic Rat Model

Abstract Background: Sinusoidal endothelial cells (SECs) in liver play important roles in hepatocyte regeneration. We recently reported placenta-derived mesenchymal stem cells (PD-MSCs) can promote hepatic regeneration in a damaged liver model via dynamic events. However, the effects of PD-MSCs on vascular structure in liver tissues remain unknown. We therefore investigated alteration of vascular structure and function in carbon tetrachloride (CCl4)-injured rat model following transplantation (Tx) with PD-MSCs. Methods: PD-MSCs were engrafted into CCl4-injured rat model via intravenous Tx. Expression markers related to angiogenic factors and Wnt signaling pathway were analyzed by quantitative real time-PCR, Western blot, and immunofluorescence in vitro and in vivo. Furthermore, endothelial permeability assay was performed to confirm the effect of PD-MSCs on the functional regeneration of injured endothelial cells in vitro co-culture system.Results: PD-MSCs were found to significantly reduce the expanded hepatic vein diameter and increased tube formation of the aorta in both in vitro and ex vivo co-culture systems. PD-MSCs also increased the expression of angiogenic factors and activated the Wnt signaling pathway. Furthermore, PD-MSCs reduced endothelial permeability via activation of β-catenin in the in vitro co-culture system. Conclusions: Taken together, PD-MSCs transplantation (PD-MSC Tx) improves the structure and function of SECs by activating Wnt signaling, which triggers hepatic regeneration, in a CCl4-injured rat model. Therefore, these findings suggest that vascular restoration induced by PD-MSCs supports liver regeneration in a hepatic failure model and can be applied as a cell-based therapy.

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Microvascular Structure and Function in Vitro

ASME 2009 7th International Conference on Nanochannels, Microchannels and Minichannels ◽

10.1115/icnmm2009-82124 ◽

2009 ◽

Author(s):

Abraham D. Stroock ◽

Nak Won Choi ◽

Tobias D. Wheeler ◽

Valerie Cross ◽

Scott Verbridge ◽

...

Keyword(s):

Mammalian Cells ◽

Structure And Function ◽

Three Dimensions ◽

Vascular Structure ◽

Biological Applications ◽

Convective Mass Transfer ◽

Negative Pressures ◽

And Function ◽

And Control

Vascular structure — a network of convective paths — is a ubiquitous element in multicellular, living systems. The key function of vascular structure in animals and plants is mediation of convective mass transfer over macroscopic distances; this transfer allows an organism to monitor and control the chemical state of its tissues. In our laboratory, we are developing methods to embed and operate microfluidic systems within tissue-like materials in order to capture this function for both biological and non-biological applications. I will present two examples to illustrate our efforts: 1) Capillary beds for the culture of mammalian cells in three-dimensions. In this section, I will discuss the development of methods both to fabricate synthetic capillary beds and to grow them directly out of endothelial cells. I will highlight how simple ideas from continuum mechanics and material science have guided our efforts. 2) Synthetic xylem networks that allow for the transpiration of water at large negative pressures. I will point out the unusual thermodynamic and transport phenomena that are involved in the transpiration process in plants. I will then present our perspectives on the design criteria for systems — synthetic and biological — that mediate this process. Finally, I will describe our experiments with “synthetic trees” in which we have reproduced the main features of transpiration. I will conclude with perspectives on applications and generalizations of both these classes of vascularized materials.

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