Creating an immune-privileged site using retinal progenitor cells and biodegradable polymers

Creating an immune-privileged site using retinal progenitor cells and biodegradable polymers
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DOI:
10.1634/stemcells.2006-0780
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发表时间:
2007-06-01
期刊:
影响因子:
5.2
通讯作者:
Young, Michael J.
Young, Michael J.
中科院分区:
医学2区
文献类型:
--
作者:
Ng, Tat Fong;Lavik, Erin;Young, Michael J.

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我们描述了使用视网膜祖细胞(RPC)和生物可降解聚合物的局部免疫豁免的创建。将小鼠RPC接种在聚(乳酸-共乙醇酸)聚合物上以产生复合移植物。将复合物或单独的RPC移植到同种异体肾包膜中。移植物在所有时间点均存活,分化为神经元和星形胶质细胞。在用干扰素γ(IFN γ)治疗后,主要组织相容性复合物抗原上调。虽然10%的IFN-γ处理的RPC移植物存活14天,66%的IFN-γ处理的复合物存活部分通过产生免疫抑制因子转化生长因子-β 2,Fas配体,和吲哚胺2,3-双加氧酶。通过接种与卵清蛋白孵育的抗原呈递细胞的复合物来测定复合物的迟发型超敏反应(DTH)。这导致了卵清蛋白特异性DTH的抑制,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特权移植物的存活(例如,胰腺、肝脏或皮肤)。
We describe the creation of local immune privilege JP) 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 (IFN gamma), major histocompatibility complex antigens were upregulated. Although 10% of IFN gamma-treated RPC grafts survived 14 days, 66% of the IFN gamma-treated composites survived in part by producing immune suppressive factors transforming growth factor-ss 2, 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).