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Viability of HEMA-MMA microencapsulated model hepatoma cells in rats and the host response
1Department of Chemical Engineering and Applied Chemistry, Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
Abstract:
Small diameter hydroxyethyl methacrylate-methyl methacrylate (HEMA-MMA; 75% HEMA) microcapsules containing an aggregate of viable rat hepatoma H4IIEC3 cells, after implantation into an omental pouch in Wistar rats, contained viable cells at 7 days but not 14 days. A similar transplantation of microencapsulated aggregates of human hepatoma HepG2 cells did not result in viable cells even at 7 days. The loss of viability was attributed to the tissue reaction, because both encapsulated cell types remained viable in vitro. However, it is not clear if the cells lost their viability in vivo, leading to the aggressive tissue reaction or if the latter caused the cells to starve or otherwise die. The tissue reactions to microcapsules containing rat or human hepatoma cells at day 1 was one cell layer thick and avascular. At later times, tissue reactions were comprised of three regions: macrophages, fibroblasts, and some foreign body giant cells apposed to the polymer membrane, a dense region of fibroblasts and collagen, and a region of vascularized granulation tissue. Prompt vascularization of the tissue reactions occurred after 4 days and was maintained for up to 14 days. Even at 14 days, immune cells were observed, suggesting a continued immune response toward antigens shed from the encapsulated cells.
Insights
Microencapsulated hepatoma cells showed reduced viability after transplantation in rats, likely due to immune and tissue reactions. Further research is needed to determine if cell death caused the reaction or vice versa.
Area of Science:
- Biomaterials Science
- Cell Biology
- Immunology
Background:
- Hydroxyethyl methacrylate-methyl methacrylate (HEMA-MMA) microcapsules are investigated for cell encapsulation.
- Hepatoma cell lines (rat H4IIEC3 and human HepG2) were used to assess microcapsule performance in vivo.
- Understanding host response to encapsulated cells is crucial for therapeutic applications.
Purpose of the Study:
- To evaluate the in vivo viability of encapsulated rat and human hepatoma cells after transplantation.
- To characterize the host tissue reaction to microencapsulated hepatoma cells.
- To investigate the interplay between cell viability and tissue response.
Main Methods:
- Small diameter HEMA-MMA microcapsules (75% HEMA) were prepared.
- Aggregates of H4IIEC3 (rat) and HepG2 (human) hepatoma cells were encapsulated.
- Microcapsules were implanted into the omental pouch of Wistar rats.
- Cell viability was assessed at 7 and 14 days post-implantation.
- Histological analysis characterized tissue reactions around the microcapsules.
Main Results:
- Encapsulated H4IIEC3 cells were viable at 7 days but not 14 days post-transplantation.
- Encapsulated HepG2 cells showed no viability even at 7 days.
- In vitro studies confirmed cell viability outside the host, suggesting in vivo factors caused cell death.
- Tissue reactions included macrophages, fibroblasts, giant cells, collagen deposition, and vascularization.
- Immune cells were present up to 14 days, indicating a sustained immune response.
Conclusions:
- HEMA-MMA microcapsules failed to maintain hepatoma cell viability in vivo beyond 7 days.
- Host tissue reactions, including inflammation and immune responses, likely contributed to cell death.
- The precise causal relationship between cell viability and tissue reaction requires further investigation.
