Scaffold implantation vs. intravenous delivery: a comparative preclinical animal study evaluating peroxisome proliferator-activated receptor gamma coactivator 1-alpha adipose-derived stem cells in liver fibrosis treatment

Article

作者: Kim, Ok-Hee ; Choi, Ho Joong ; Lee, Dosang ; Ahn, Joseph ; Hong, Ha-Eun ; Kim, Say-June ; Park, Jung Hyun

PurposeRegenerative medicine is expected to offer an alternative to liver transplantation for treating liver diseases in the future, with one significant challenge being the establishment of an effective stem cell administration route. This study assessed the antifibrogenic effects of adipose-derived stem cells (ASCs) in a liver fibrosis mouse model, focusing on 2 methods of delivery: intravenous injection and scaffold implantation.MethodsAn extracellular matrix mimic scaffold was utilized for culturing peroxisome proliferator-activated receptor gamma coactivator 1-alpha-overexpressing ASCs (tASCs). These scaffolds, laden with tASCs, were then implanted subcutaneously in mice exhibiting liver fibrosis. In contrast, the Cell groups received biweekly intravenous injections of tASCs for 4 weeks. After 4 weeks, tissue samples were harvested from the euthanized mice for subsequent analysis.ResultsReal-time PCR and Western blot analyses on liver tissues, focusing on markers like alpha-smooth muscle actin (α-SMA), matrix metalloproteinase-2, and transforming growth factor-beta 1 (TGF-β1), showed that both delivery routes substantially lowered fibrotic and inflammatory markers compared to controls (P < 0.05), with no significant differences between the routes. Histological examinations, along with immunohistochemical analysis of α-SMA, collagen type I alpha, and TGF-β1, revealed that the scaffold implantation approach resulted in a greater reduction in fibrosis and lower immunoreactivity for fibrotic markers than intravenous delivery (P < 0.05).ConclusionThese findings indicate that delivering tASCs via a scaffold could be more effective, or at least similarly effective, in treating liver fibrosis compared to intravenous delivery. Scaffold implantation could offer a beneficial alternative to frequent intravenous treatments, suggesting its potential utility in clinical applications for liver disease treatment.

2024-01-01·Annals of Surgical Treatment and Research

Pioneering PGC-1α–boosted secretome: a novel approach to combating liver fibrosis

Article

作者: Choi, Ho Joong ; Kim, Ok-Hee ; Park, Jung Hyun ; Hong, Tae Ho ; Kim, Say-June ; Lee, Sang Chul ; Kim, Kee-Hwan ; Lee, Dosang ; Seo, Chang Ho ; Na, Gun Hyung

PurposeLiver fibrosis is a critical health issue with limited treatment options. This study investigates the potential of PGC-Sec, a secretome derived from peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)-overexpressing adipose-derived stem cells (ASCs), as a novel therapeutic strategy for liver fibrosis.MethodsUpon achieving a cellular confluence of 70%-80%, ASCs were transfected with pcDNA-PGC-1α. PGC-Sec, obtained through concentration of conditioned media using ultrafiltration units with a 3-kDa cutoff, was assessed through in vitro assays and in vitro mouse models.ResultsIn vitro, PGC-Sec significantly reduced LX2 human hepatic stellate cell proliferation and mitigated mitochondrial oxidative stress compared to the control-secretome. In an in vivo mouse model, PGC-Sec treatment led to notable reductions in hepatic enzyme activity, serum proinflammatory cytokine concentrations, and fibrosis-related marker expression. Histological analysis demonstrated improved liver histology and reduced fibrosis severity in PGC-Sec-treated mice. Immunohistochemical staining confirmed enhanced expression of PGC-1α, optic atrophy 1 (a mitochondrial function marker), and peroxisome proliferator-activated receptor alpha (an antifibrogenic marker) in the PGC-Sec-treated group, along with reduced collagen type 1A expression (a profibrogenic marker).ConclusionThese findings highlight the therapeutic potential of PGC-Sec in combating liver fibrosis by enhancing mitochondrial biogenesis and function, and promoting antifibrotic processes. PGC-Sec holds promise as a novel treatment strategy for liver fibrosis.

Biomedicines

Intraparenchymal Penicillin G Injection Promotes Wound Healing and Lowers POPF in Pigs After Pancreatic Surgery

Article

作者: Hong, Tae Ho ; Kim, Kee-Hwan ; Kim, Ok-Hee ; Lee, Dosang ; Kim, Say-June ; Park, Jung Hyun ; Han, Jae Hyun ; Choi, Ho Joong ; Jeon, Sang-Jin

Background: Postoperative pancreatic fistula (POPF) is a significant complication following pancreatic surgery, considerably influenced by the texture of the pancreatic tissue. This study aims to explore the potential of Penicillin G (PG) in reducing the severity of POPF in a porcine surgical model. Study Design: After performing distal pancreatectomy with pancreaticojejunostomy (PJ), pigs were administered either normal saline or varying concentrations of PG (0.75, 1.5, and 3.0 mM) at the PJ site. The study estimated POPF by measuring pancreatic hardness, tensile force, fibrosis, and amylase levels in Jackson-Pratt (JP) drain samples. Results: Intraparenchymal PG injection significantly increased pancreatic hardness and tensile force (p < 0.05) while upregulating profibrotic markers like MMP2 and TGF-β1, indicating enhanced fibrosis (p < 0.05). Importantly, these profibrotic changes reverted to baseline levels by POD 14, suggesting reversible fibrosis without lasting consequences. The 0.75 PG and 1.5 PG groups exhibited significantly lower JP amylase levels than the control group on both POD 3 and POD 4 (p < 0.05). Notably, the 0.75 PG group also demonstrated the highest survival rate compared to the 1.5 PG and NS groups (p < 0.05). Conclusions: The intrapancreatic PG injection could effectively reduce the severity of POPF by promoting wound healing through intensified fibrosis around the PJ site.

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