Ng Tat Fong, Lavik Erin, Keino Hiroshi, Taylor Andrew W, Langer Robert S, Young Michael J
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, Massachusetts 02114, USA.
Stem Cells. 2007 Jun;25(6):1552-9. doi: 10.1634/stemcells.2006-0780.
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.
我们描述了利用视网膜祖细胞(RPCs)和可生物降解聚合物创建局部免疫赦免(IP)的方法。将小鼠RPCs接种在聚乳酸-乙醇酸聚合物上以生成复合移植物。将复合材料或单独的RPCs移植到同种异体肾包膜中。移植物在所有时间点均存活,并分化为神经元和星形胶质细胞。在用γ干扰素(IFNγ)处理后,主要组织相容性复合体抗原上调。尽管10%经IFNγ处理的RPC移植物存活了14天,但66%经IFNγ处理的复合材料通过产生免疫抑制因子转化生长因子-β2、Fas配体和吲哚胺2,3-双加氧酶而部分存活。通过将复合材料与用卵清蛋白孵育的抗原呈递细胞一起接种,对复合材料进行迟发型超敏反应(DTH)检测。这导致卵清蛋白特异性DTH受到抑制,表明由可生物降解聚合物和中枢神经系统祖细胞组成的复合移植物可用于产生局部IP。该技术可用于促进非赦免移植物(如胰腺、肝脏或皮肤)的存活。潜在利益冲突的披露见本文末尾。