Efficacy of Autologous Skeletal Myoblast Cell Sheet Transplantation for Liver Regeneration in Liver Failure

Islet transplantation (ITx) is an established and safe alternative to pancreas transplantation for type 1 diabetes mellitus (T1DM) patients. However, most ITx recipients lose insulin independence by 3 years after ITx due to early graft loss, such that multiple donors are required to achieve insulin independence. In the present study, we investigated whether skeletal myoblast cells could be beneficial for promoting angiogenesis and maintaining the differentiated phenotypes of islets. In vitro experiments showed that the myoblast cells secreted angiogenesis-related cytokines (vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and stromal-derived factor-1α (SDF-1α)), contributed to maintenance of differentiated islet phenotypes, and enhanced islet cell insulin secretion capacity. To verify these findings in vivo, we transplanted islets alone or with myoblast cells under the kidney capsule of streptozotocin-induced diabetic mice. Compared with islets alone, the group bearing islets with myoblast cells had a significantly lower average blood glucose level. Histological examination revealed that transplants with islets plus myoblast cells were associated with a significantly larger insulin-positive area and significantly higher number of CD31-positive microvessels compared to islets alone. Furthermore, islets cotransplanted with myoblast cells showed JAK-STAT signaling activation. Our results suggest two possible mechanisms underlying enhancement of islet graft function with myoblast cells cotransplantation: “indirect effects” mediated by angiogenesis and “direct effects” of myoblast cells on islets via the JAK-STAT cascade. Overall, these findings suggest that skeletal myoblast cells enhance the function of transplanted islets, implying clinical potential for a novel ITx procedure involving myoblast cells for patients with diabetes.

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Effect of Adipose-Derived Stem Cells Embedded in Fibrin Gel on Post-Hepatectomy Liver Regeneration: A Therapeutic Model Inducing a Paracrine Effect

Imamura,

Tomimaru,

Kobayashi

et al. 2024

Preprint

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We investigated the potential of adipose-derived stem cells (ADSCs) in preventing post-hepatectomy liver failure, emphasizing the necessity of direct administration using a scaffold to harness their paracrine effects. A fibrin gel scaffold was employed for ADSCs (gelADSCs) to assess their therapeutic impact on liver regeneration in both in vitro and in vivo settings. Experiments were conducted on C57BL/6 mice with normal livers and those with chronic hepatitis. We also explored the role of extracellular vesicles (EVs) secreted by ADSCs in conjunction with fibrin gel. GelADSCs showed sustained release of hepatocyte growth factor, vascular endothelial growth factor, and stromal cell–derived factor 1 for at least 7 days in vitro. In vivo, gel ADSCs significantly enhanced postoperative liver regeneration by upregulating the cell cycle and fatty acid oxidation in both normal and chronically hepatitis-affected mice. The therapeutic effects of gel ADSCs were notably superior to those of intravenously administered ADSCs, especially in mice with chronic hepatitis. Increased EV secretion associated with fibrin gel use was significantly linked to enhanced liver regeneration post-surgery through the promotion of fatty acid oxidation. The findings underscore the enhanced therapeutic potential of gelADSCs, particularly in the context of chronic hepatitis, compared to intravenous administration.

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Efficacy of Autologous Skeletal Myoblast Cell Sheet Transplantation for Liver Regeneration in Liver Failure

Cited by 3 publications

References 46 publications

Application of a laparoscopic device for cell-derived sheet transplantation on the liver in a porcine model

Application of a laparoscopic device for cell-derived sheet transplantation on the liver in a porcine model

Skeletal Myoblast Cells Enhance the Function of Transplanted Islets in Diabetic Mice

Effect of Adipose-Derived Stem Cells Embedded in Fibrin Gel on Post-Hepatectomy Liver Regeneration: A Therapeutic Model Inducing a Paracrine Effect

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