Abstract
BackgroundWith the progress in medicine, the average human life expectancy is continuously increasing. At the same time, the number of patients who require full organ transplantations is augmenting. Consequently, new strategies for cell transplantation are the subject of great interest.Methodology/Principal FindingsThis work reports the design, the synthesis and the characterisation of robust and biocompatible mineralised beads composed of two layers: an alginate-silica composite core and a Ca-alginate layer. The adequate choice of materials was achieved through cytotoxicity LDH release measurement and in vitro inflammatory assay (IL-8) to meet the biocompatibility requirements for medical purpose. The results obtained following this strategy provide a direct proof of the total innocuity of silica and alginate networks for human cells as underscored by the non-activation of immune defenders (THP-1 monocytes). The accessible pore size diameter of the mineralised beads synthesized was estimated between 22 and 30 nm, as required for efficient immuno-isolation without preventing the diffusion of nutrients and metabolites. The model human cells, HepG2, entrapped within these hybrid beads display a high survival rate over more than six weeks according to the measurements of intracellular enzymatic activity, respiration rate, as well as the “de novo” biosynthesis and secretion of albumin out of the beads.Conclusions/SignificanceThe current study shows that active mammalian cells can be protected by a silica-alginate hybrid shell-like system. The functionality of the cell strain can be maintained. Consequently, cells coated with an artificial and a biocompatible mineral shell could respond physiologically within the human body in order to deliver therapeutic agents in a controlled fashion (i.e. insulin), substituting the declining organ functions of the patient.
Highlights
Since the original idea published in 1933 by Bisceglie [1], significant advances have been achieved to develop immunoisolation methods for long-term transplantation of xenogenic cells or tissues
Conclusions/Significance: The current study shows that active mammalian cells can be protected by a silica-alginate hybrid shell-like system
If a molecular weight (MW) cut-off of around 150 kDa is generally accepted [6,7], which is the MW of the immunoglobulin G (IgG), the diameter related to this value is still debated
Summary
Since the original idea published in 1933 by Bisceglie [1], significant advances have been achieved to develop immunoisolation methods for long-term transplantation of xenogenic cells or tissues. Immuno-isolation should be understood as a way to protect cells against mechanical stress and rejection from the immune system of the host body while allowing the diffusion of nutrients, oxygen and metabolites. They are separated by a biocompatible and semi-permeable membrane. The porosity of this cell-entrapping material is a key parameter for successful immuno-isolation. Apart from porosity issues, the robustness and the biocompatibility of the semi-permeable system are important features for the successful transplantation of cells. New strategies for cell transplantation are the subject of great interest
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