Macro‐encapsulation of mesenchymal stem cells in acute and chronic liver injury animal models

Abstract

Background and Aim: Stem cell treatments using scaffolds for liver disease have been well studied. However, macro-encapsulation of mesenchymal stem cells (MSCs) to minimize or inhibit stem cell homing has not been evaluated. Here, we conducted a proof-ofconcept study using MSCs macro-encapsulated in poly lactic-co-glycolic acid in liver disease models. Methods: Poly lactic-co-glycolic acid semipermeable membranes (surface pore size up to 40 μm) were used as the macro-encapsulation system. Macro-encapsulated pouches were loaded with MSCs and sealed. Each pouch was implanted in the subcutaneous region of the dorsum or interlobular space of the liver. Acute liver injury was induced using thioacetamide intraperitoneal injection thrice a week. For the chronic liver fibrosis model, thioacetamide dose was gradually increased, starting from 100 to 400 mg/kg over 16 weeks (thrice a week). Results: In the acute liver injury model, the treated groups showed decreased liver inflammation and necrosis compared with the control. Hepatic fibrosis decreased in the treated group in the chronic liver fibrosis model compared with that in the control group. Encapsulated MSCs exhibited changed cell morphology and characteristics after implantation, showing increased periodic acid-Schiff staining and CYP2E1 expression. Migration and homing of MSCs into the liver was not observed. Under hypoxic conditions, macro-encapsulated MSCs secreted more growth hormones, including vascular endothelial growth factor, platelet-derived growth factor, angiopoietin-2, and placental growth factor, than monolayered MSCs in vitro. Conclusions: Macro-encapsulated MSCs attenuate hepatic inflammation and fibrosis by upregulating hypoxia-induced growth hormone secretion in liver disease models.

Microencapsulation-based cell therapies

“…This polymer is of interest due to its FDA approval and tuneable degradation under biological conditions with degradation products that are already produced in vivo. However, studies have also demonstrated that PLGA can cause inflammation and toxicity [ 17 ]. In a recent study, PLGA/Pluronic membranes were synthesised and converted into envelope-shaped pouches with one side open.…”

Recent advances in the immunomodulation mechanism of mesenchymal stem cell therapy in liver diseases

“…Moreover, Kang et al . had confirmed that encapsulating MSCs with poly lactic‐co‐glycolic acid would increase the secretion of cytokines from MSCs 11 . Importantly, immune regulation is one of the most critical mechanisms by which MSCs can ameliorate the symptoms of several intractable diseases 12 .…”

“…6 Moreover, Kang et al had confirmed that encapsulating MSCs with poly lactic-co-glycolic acid would increase the secretion of cytokines from MSCs. 11 Importantly, immune regulation is one of the most critical mechanisms by which MSCs can ameliorate the symptoms of several intractable diseases. 12 However, previous studies on the immune regulatory mechanisms of MSCs have not elucidated their modulatory effects on immune cells in detail as we do.…”

Design and Usability Evaluations of a 3D‐Printed Implantable Drug Delivery Device for Acute Liver Failure in Preclinical Settings

“…macro-encapsulation technique comprising mesenchymal stem cells to treat acute and chronic liver injuries. [9] However, the strategy used in the previous study had the following limitations: difficult to repeatedly deliver the API through refilling and difficult to properly design the shape of the implantable delivery device to fit the damaged tissues.…”