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

Lee, Y.B.; Choi, Joan; Kim, E.N.; Seok, Jo Woon; Lee, H.-J.; Kim, G.J.

doi:10.1016/s0168-8278(18)31162-0

Cited by 1 publication

(1 citation statement)

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“…These previous reports support our conclusion that mtDNA and ATP synthesis are increased in liver tissues during liver regeneration following transplantation of functionally enhanced PD-MSCs. Additionally, we recently reported that mitochondrial energy metabolism following cellular ATP production was restored by naïve PD-MSC transplantation in a cholestatic liver disease model [47]. Our data elucidated that compared with naïve PD-MSCs, PD-MSCs PRL−1 generated using non-viral AMAXA system transplantation promoted mtDNA synthesis.…”

Section: Discussionmentioning

confidence: 60%

Enhanced PRL-1 expression in placenta-derived mesenchymal stem cells accelerates hepatic function via mitochondrial dynamics in a cirrhotic rat model

Kim

Choi

Jun

et al. 2020

Preprint

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Background: Placenta-derived mesenchymal stem cells (PD-MSCs) have been highlighted as an alternative cell therapy agent that becomes a next-generation stem cell treatment because of several advantages, including therapeutic effects in regenerative medicine and potential as vehicles for targeted gene delivery systems. Phosphatase of regenerating liver-1 (PRL-1), an immediate early gene, plays a critical role during liver regeneration. However, whether enhanced PRL-1 expression in cirrhotic liver accelerates the mitochondrial metabolic state for hepatic regeneration remains unknown. Here, we generated enhanced PRL-1 in PD-MSCs (PD-MSCsPRL-1, PRL-1+) using lentiviral and nonviral gene delivery systems and investigated mitochondrial functions by PD-MSCPRL-1 transplantation for hepatic functions in a rat model with bile duct ligation (BDL). Methods: PD-MSCsPRL-1 were generated by lentiviral and non-viral AMAXA gene delivery systems and analyzed for their characteristics and mitochondrial metabolic functions. Sprague-Dawley (SD) rats induced liver cirrhosis using common BDL for 10 days. PKH67+ naïve and PD-MSCsPRL-1 using a non-viral system (2x106 cells/animal) were intravenously administered into cirrhotic rats. The animals were sacrificed at 1, 2, 3, and 5 weeks after transplantation and engraftment of stem cells, and histopathological analysis and hepatic mitochondrial functions were performed. Results: PD-MSCsPRL-1 using lentiviral and non-viral AMAXA systems were successfully generated, and they maintained characteristics similar to those of naïve cells. PD-MSCsPRL-1 improved respirational metabolic states in mitochondria compared with naïve cells. In particular, compared with mitochondria in PD-MSCsPRL-1 generated by the nonviral AMAXA system, mitochondria in PD-MSCsPRL-1 generated by the lentiviral system showed a significant increase in the respirational metabolic state, including ATP production and mitochondrial biogenesis (*p<0.05). Furthermore, transplantation of PD-MSCsPRL-1 using a nonviral AMAXA system promoted engraftment into injured target liver tissues of a rat cirrhotic model with BDL and enhanced the metabolism of mitochondria via increased mtDNA and ATP production, thereby improving therapeutic efficacy. Conclusions: Our findings will further our understanding of the therapeutic mechanism of enhanced MSCs and provide useful data for the development of next-generation MSC-based cell therapy and therapeutic strategies for regenerative medicine in liver disease.

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Section: Discussionmentioning

confidence: 60%