Mesenchymal stem cells seeded on a human amniotic membrane improve liver regeneration and mouse survival after extended hepatectomy

Abstract

Liver failure remains the leading cause of post-operative mortality after hepatectomy. This study investigated the effect of treatment with allogenic mesenchymal stem cells (MSCs) on survival and liver regeneration 48 hr and 7 days after 80% hepatectomy in C57Bl/6 mice. To optimize their biodistribution, MSCs were grown on acellular human amniotic membranes (HAM) and applied as a patch on the remnant liver. This approach was compared with MSC infusion and HAM patch alone. Hepatectomized mice without any treatment were used as control group. Survival rate was calculated and biological and histopathological parameters were analysed to monitor liver function and regeneration. MSCs grown on HAM retained their ability to proliferate, to differentiate into osteoblasts and adipocytes and to respond to pro-inflammatory stimuli. Extended hepatectomy (80%) led to liver failure that resulted in death within 72 hr in 76% of mice. MSC infusion showed an early but transitory positive effect on survival. MSC/HAM patches stimulated regeneration and significantly improved survival rate (54% vs. 24% in the control group at 7 days). They also decreased the severity of hepatectomy-induced steatosis, suggesting a modulation of lipid metabolism in hepatocytes. MSCs were still present on HAM at Days 2 and 7 posthepatectomy. In conclusion, engineered tissue constructs that combine MSCs and HAM improve survival and liver regeneration after 80% hepatectomy in mice. These encouraging results pave the way to potential clinical application.

Tauroursodeoxycholic Acid Protects against the Effects of P-Cresol-Induced Reactive Oxygen Species via the Expression of Cellular Prion Protein

“…Previous studies have suggested potential application of MSCs in the treatment of injured tissues [ 31 , 32 ]. However, there are limitations of such applications because of poor conditions near the application area from pathophysiological conditions including high ROS levels, inflammation, and apoptosis [ 33 ].…”

Human Stem Cells Promote Liver Regeneration After Partial Hepatectomy in BALB/C Nude Mice

“…Steatosis was evaluated as follows: (a) the percentage of steatotic cells relative to the total number of cells per section by manual counting all cells containing one or more lipid droplets, and (b) the number of lipid droplets in hepatocytes was used to define steatosis as mild (one droplet/cell), moderate (few droplets/cells), or severe (numerous droplets filling the cytoplasm). 17 Histological evaluation was conducted by two blinded observers (A.A. and S.W).…”

“…The administration of multipotent cells, for example, mesenchymal stem cells (MSC) and hematopoietic stem cells (HSC), and their potential for modulating vascular inflammation and organ regeneration has caught the attention of various groups during the last years. Others and we have gained broad experiences early with multipotent stem cells in different experimental liver failure models 12,13,[15][16][17][18][19] and in clinical settings. [20][21][22] Although, immunomodulatory and regenerative capacities of multipotent stem cells have been confirmed in different experimental settings, the administration of MSC to investigate liver regeneration in a clinical setting has not been investigated so far.…”

Development of Injectable Amniotic Membrane Matrix for Postmyocardial Infarction Tissue Repair

“…The matrix derived from human amniotic membrane has various components and bioactivities, which allow such matrix to be widely applied in corneal transplantation, retinal regeneration, liver regeneration, and wound healing. [21][22][23][24] Due to its anti-inflammatory effects, anti-fibrotic effect, and angiogenic potentials, [25][26][27][28] we postulate that materials derived from hAM could beneficial for restoring cardiac function following MI.…”