Effect of implanted microencapsulated xenogeneic cells on the recipient immune system.
Published: 2004
Language: eng
Number of pages: 149
Description: Remarkably, all such co-implants suppressed splenocyte proliferation at 10 days post-implant, though this effect disappeared by 60 days. In contrast, the antibody response was equal to or greater than that for a skin graft alone at both timepoints. Th1/2 polarization did not explain these observations, since it did not correlate with suppression of splenocyte proliferation, but rather depended on mode of xenogeneic cell delivery.Microencapsulation has potential clinical application for islet transplantation. To better understand the ongoing destructive host response, I examined whether the adaptive immune system recognised encapsulated xenogeneic cells, and how immune responses interacted with implanted biomaterials.The influence of Th1/2 bias did not explain the observed suppression. Encapsulated xenogeneic cells elicited a consistent Th2 response, unencapsulated cells elicited a mixed response, and skin xenografts showed an initial Th2 response that transformed to a Th1 response by 60 days based on antibody isotypes and cytokines.These novel effects of biomaterials have wide relevance: most tissue-engineered constructs contain biomaterials and will elicit immune responses, so suppressions mediated by biomaterials merits further examination and should affect future design approaches.I then monitored host immune responses to skin xenografts accompanied by one of three co-implants: encapsulated xenogeneic cells; unprotected cells accompanied by the encapsulation biomaterials; and encapsulation-biomaterials without cells.Encapsulation did not prevent a strong host antibody response (day 10 and day 60). Splenocyte proliferation in vitro did not differ whether primed by implanted, encapsulated cells, or unencapsulated cells (60 days). Thus, capsule membranes did not prevent indirect recognition of shed antigens. However, splenocyte proliferation to these cell/biomaterial implants was delayed compared to skin xenografts: after 10 days implantation, proliferation was dramatically lower than to skin grafts, though the difference disappeared by 60 days. This transient T-cell suppression was unexpected, since encapsulated cell viability was already compromised by 10 days.Mice were implanted intraperitoneally with encapsulated and unencapsulated xenogeneic cells, and the responses were compared with xenografted skin (positive control). Splenocyte proliferation upon re-challenge in vitro, antibody titre in serum, and Th1/2 polarisation (by IL-4 and IFN-gamma in splenocyte challenge supernatants and IgGl and IgG2a antibody isotypes in serum) were measured.
Notes: Adviser:  Michael V. Sefton.

Thesis (Ph.D.)--University of Toronto, 2004.

Electronic version licensed for access by U. of T. users.

Source: Dissertation Abstracts International, Volume: 65-05, Section: B, page: 2495.