The effect of covalent cross-links between the membrane components of microcapsules on the dissemination of encapsulated malignant cells.
Stem cells and immortalized cells have considerable therapeutic potential but present risks of malignant transformation. Cell microencapsulation allows transplantation without immunosuppression. We have developed a method for microencapsulating living cells within covalently cross-linked membranes that are chemically and mechanically extremely resistant. We provide herein direct evidence that these microcapsules can prevent malignant cell dissemination. When 20,000 or more nonencapsulated EL-4 thymoma cells were implanted intraperitoneally in mice, all recipients died with widespread metastasis within 26.3+/-1.0 days. All recipients of 250,000 EL-4 cells microencapsulated in covalently cross-linked membranes were living and disease-free, 150 days post-implantation. Encapsulation in standard microcapsules only slightly delayed the recipient death. Pancreatic islets transplanted using either type of microcapsule presented similar survival. We conclude that microencapsulation in covalently cross-linked membranes prevents malignant cell dissemination.
Maisonneuve-Rosemont Hospital Research Centre, Université de Montréal, 5415 boul. de l'Assomption, Montréal, Québec, Canada H1T 2M4.
Julie
J
Dusseault
Geneviève
G
Langlois
Marie-Christine
MC
Meunier
Martin
M
Ménard
Claude
C
Perreault
Jean-Pierre
JP
Hallé
D000818:Animals; D015415:Biomarkers; D002214:Capsules; D045744:Cell Line, Tumor; D002470:Cell Survival; D003432:Cross-Linking Reagents / Q000737:chemistry*; D007515:Islets of Langerhans / Q000166:cytology; D008297:Male; D051379:Mice; D008954:Models, Biological; D018800:Thy-1 Antigens / Q000378:metabolism; D013945:Thymoma / Q000378:metabolism / Q000473:pathology; D013953:Thymus Neoplasms / Q000378:metabolism / Q000473:pathology
D015415:Biomarkers; D002214:Capsules; D003432:Cross-Linking Reagents; D018800:Thy-1 Antigens