Regulating MCP-1 diffusion in affinity hydrogels for enhancing immuno-isolation.
Regulating MCP-1 diffusion in affinity hydrogels for enhancing immuno-isolation.
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DOI：
10.1016/j.jconrel.2009.11.022
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发表时间：
2010-03-19
影响因子：
10.8
通讯作者：
Anseth, Kristi S.
中科院分区：
文献类型：
--
作者：
Lin, Chien-Chi;Boyer, Patrick D.;Aimetti, Alex A.;Anseth, Kristi S.
使用半渗透性水凝胶递送细胞正在成为基于细胞的疗法和再生医学应用中越来越重要的方向。合成水凝胶已经用生物活性基序官能化，以使原本惰性的聚合物网络响应。然而，很少有人致力于创造能够阻滞由合成载体递送的细胞分泌的小抗原分子转运的免疫隔离材料。为了实现开发完整的免疫隔离聚合物屏障的目标，开发了亲和肽官能化的PEG水凝胶，其具有隔离单核细胞趋化蛋白1（MCP-1）的能力，MCP-1是已知诱导单核细胞、树突状细胞和记忆T细胞的趋化性的趋化因子。从CCR 2（MCP-1的G蛋白偶联受体）中鉴定出能够螯合MCP-1的亲和肽，并通过硫醇-丙烯酸酯光聚合将其掺入PEG水凝胶中。从PEG水凝胶释放包封的重组MCP-1容易通过以下方式调节：（1）在网络内掺入亲和肽;和/或（2）改变亲和肽和交联位点之间的间隔距离。此外，当胰腺β-细胞包封在这些新型肽官能化水凝胶内时，细胞分泌的MCP-1的释放显著减少，证明了这种新的凝胶制剂通过减少宿主单核细胞和其他免疫细胞的募集和活化来减少宿主对移植细胞的先天免疫应答的潜力。
Delivering cells using semi-permeable hydrogels is becoming an increasingly important direction in cell based therapies and regenerative medicine applications. Synthetic hydrogels have been functionalized with bioactive motifs to render otherwise inert polymer networks responsive. However, little effort has been focused on creating immuno-isolating materials capable of retarding the transport of small antigenic molecules secreted from the cells delivered with the synthetic carriers. Toward the goal of developing a complete immuno-isolation polymeric barrier, affinity peptide-functionalized PEG hydrogels were developed with the ability to sequester monocyte chemotactic protein 1 (MCP-1), a chemokine known to induce the chemotaxis of monocytes, dendritic cells, and memory T-cells. Affinity peptides capable of sequestering MCP-1 were identified from CCR2 (a G protein-coupled receptor for MCP-1) and incorporated within PEG hydrogels via a thiol-acrylate photopolymerization. The release of encapsulated recombinant MCP-1 from PEG hydrogels is readily tuned by: (1) incorporating affinity peptides within the network; and/or (2) altering the spacer distance between the affinity peptide and the crosslinking site. Furthermore, when pancreatic β-cells were encapsulated within these novel peptide-functionalized hydrogels, the release of cell-secreted MCP-1 was significantly reduced, demonstrating the potential of this new gel formulation to reduce the host innate immune response to transplanted cells by decreasing the recruitment and activation of host monocytes and other immune cells.
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DOI：
10.1084/jem.184.2.569
发表时间：
1996-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Loetscher P;Seitz M;Baggiolini M;Moser B
通讯作者：
Moser B
影响因子：
3.7
作者：
Lin CC;Anseth KS
通讯作者：
Anseth KS
影响因子：
6.2
作者：
Lin, Chien-Chi;Anseth, Kristi S.
通讯作者：
Anseth, Kristi S.
影响因子：
19
作者：
Cheung, Charles Y.;McCartney, Suzanne J.;Anseth, Kristi S.
通讯作者：
Anseth, Kristi S.
影响因子：
2.6
作者：
Aronovitz, Amy;Josefson, Jami;Lowe, William L., Jr.
通讯作者：
Lowe, William L., Jr.