Creating an immune-privileged site using retinal progenitor cells and biodegradable polymers.
We describe the creation of local immune privilege (IP) using retinal progenitor cells (RPCs) and biodegradable polymers. Murine RPCs were seeded on poly(lactic-coglycolic acid) polymers to generate composite grafts. Composites or RPCs alone were transplanted into allogeneic kidney capsules. Grafts survived at all time points, differentiating into neurons and astrocytes. Upon treatment with interferon gamma (IFNgamma), major histocompatibility complex antigens were upregulated. Although 10% of IFNgamma-treated RPC grafts survived 14 days, 66% of the IFNgamma-treated composites survived in part by producing immune suppressive factors transforming growth factor-beta2, Fas ligand, and indoleamine 2,3-dioxygenase. The composites were assayed for delayed-type hypersensitivity (DTH) by seeding composites with antigen-presenting cells incubated with ovalbumin. This resulted in suppression of ovalbumin-specific DTH, indicating that composite grafts consisting of biodegradable polymers and central nervous system progenitor cells can be used to generate local IP. This technology may be used to promote the survival of nonprivileged grafts (e.g., pancreas, liver, or skin). Disclosure of potential conflicts of interest is found at the end of this article.
Ng
Tat Fong
TF
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, Massachusetts 02114, USA.
Lavik
Erin
E
Keino
Hiroshi
H
Taylor
Andrew W
AW
Langer
Robert S
RS
Young
Michael J
MJ
D020341:Absorbable Implants; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006016:Glycolates / Q000494:pharmacology; D006968:Hypersensitivity, Delayed; D007371:Interferon-gamma / Q000494:pharmacology; D007668:Kidney; D019344:Lactic Acid; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D012160:Retina / Q000166:cytology* / Q000276:immunology / Q000637:transplantation*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D023001:Transplantation Tolerance / Q000187:drug effects* / Q000276:immunology; D016042:Transplantation, Heterotopic; D014184:Transplantation, Homologous
D001672:Biocompatible Materials; D006016:Glycolates; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007371:Interferon-gamma