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Encapsulation Thermogenic Preadipocytes for Transplantation into Adipose Tissue Depots
Published on: June 2, 2015
Effect of microcapsule composition and short-term immunosuppression on intraportal biocompatibility
Christian Toso1, Zoltan Mathe, Philippe Morel
1Centre d'isolement et de transplantation cellulaire, Service de chirurgie viscérale, Hôpital Universitaire, 4, rue Micheli-du-Crest, CH-1211 Geneva 14, Switzerland. christian.toso@hcuge.ch
Abstract:
With higher nutrient and oxygen supply and close contact to blood, the portal vein is a possible alternative to the peritoneal cavity for transplantation of encapsulated cells. Data regarding intraportal biocompatibility of microcapsules are lacking. Microcapsules were built from five alginate types differing in their molar mass and mannuronic/guluronic acid ratios by complex formation with divalent cations (barium or calcium) or mixtures of divalent cations and polycations. They were injected in the portal vein of rats, and cellular and fibrotic pericapsular infiltration thickness was measured 3 and 7 days after implantation. Overgrowth was characterized using various stainings or immunohistochemistry (hematoxylin and eosin, Giemsa, ED-1 for monocyte/macrophage, alpha-actin for myofibroblasts, CD31 for endothelial cells). The impact of short-term immunosuppression (gadolinium-chloride IV 20 mg/kg/day on days--1 and 4 as well as 10 days of rapamycin PO 1 mg/kg/day, tacrolimus PO 3 mg/kg/day, or combinations of rapamycin/tacrolimus or gadolinium/tacrolimus) was further assessed 3, 7, and 42 days after implantation. Overall, overgrowth increased from day 3 to day 7 (p < 0.05). Three and 7 days after implantation, polycation-containing microcapsules induced more reaction than microbeads (p < 0.0001 and p < 0.01). Considering polycation-free beads, barium-alginate induced the weakest reaction. Biocompatibility of microbeads was independent of mannuronic/guluronic acid ratio and molar mass of the alginate. Infiltration was mainly a monocyte/macrophage-rich foreign body reaction, but an eosinophil-containing immunoallergic reaction was also observed. Short-term immunosuppression significantly reduced infiltration in all conditions and up to 42 days after implantation. Biocompatibility after intraportal infusion was best for barium-alginate microbeads and poorest for polycation-containing microcapsules. Short- and long-term overgrowth could be significantly reduced by short-term immunosuppression.
Insights
The portal vein offers a nutrient-rich environment for cell transplantation. Barium-alginate microcapsules show the best biocompatibility, with immunosuppression significantly reducing adverse reactions.
Area of Science:
- Biomaterials Science
- Transplantation Biology
- Vascular Surgery
Background:
- The portal vein is a potential site for encapsulated cell transplantation due to its vascularization.
- Limited data exists on the intraportal biocompatibility of microcapsules.
Purpose of the Study:
- To evaluate the biocompatibility of various microcapsule formulations within the rat portal vein.
- To assess the impact of short-term immunosuppression on microcapsule integration.
Main Methods:
- Microcapsules were fabricated from five alginate types, complexed with barium, calcium, or polycations.
- Microcapsules were implanted into the rat portal vein, with analysis at 3, 7, and 42 days.
- Immunohistochemistry and various stainings were used to characterize cellular infiltration and fibrotic reactions.
Main Results:
- Microcapsule overgrowth increased from day 3 to day 7.
- Polycation-containing microcapsules elicited a stronger foreign body reaction than polycation-free beads.
- Barium-alginate microcapsules demonstrated the weakest cellular and fibrotic infiltration.
- Short-term immunosuppression significantly reduced infiltration, improving long-term biocompatibility.
Conclusions:
- Barium-alginate microcapsules are the most biocompatible for intraportal transplantation.
- Short-term immunosuppression effectively mitigates adverse inflammatory and fibrotic responses.
- The portal vein is a viable site for encapsulated cell delivery, with careful material selection and immunosuppression strategies.
