ROS-scavenging hybrid hydrogel for genetically engineered stem cell delivery and limb ischemia therapy
ROS-scavenging hybrid hydrogel for genetically engineered stem cell delivery and limb ischemia therapy
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用于基因工程干细胞输送和肢体缺血治疗的ROS清除混合水凝胶
DOI：
10.1016/j.cej.2021.131504
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发表时间：
2021-12
影响因子：
15.1
通讯作者：
Xiang Qiuling
中科院分区：
文献类型：
--
作者：
Saw Phei Er;Zhang Zhen;Chen Yangyang;Li Senlin;Huang Linzhuo;Zhang Chi;Zhao Qianqian;Xu Xiaoding;Xiang Qiuling
干细胞治疗是治疗缺血性疾病如严重肢体缺血（CLI）的一种有前途的策略。主要障碍是移植干细胞的存活率低和效率低。仿生支架如可注射水凝胶已经显示出促进细胞保留和存活的能力。然而，局部缺血微环境，特别是高水平的活性氧（ROS）通常会诱导细胞丢失和功能障碍，从而导致不满意的治疗结果。在此，我们开发了一种由天然I型胶原和黑色素纳米颗粒（MeNPs）组成的新型可注射混合水凝胶，用于递送Gremlin 1（Grem 1）过表达的间充质干细胞（Grem 1-MSCs）和CLI治疗。将该细胞递送系统局部注射到小鼠缺血肢体后，胶原的热触发原位凝胶化可以维持Grem 1-MSCs在注射部位，并且包埋在水凝胶框架中的MeNPs可以通过清除ROS来调节缺血微环境，以促进植入的干细胞的存活。由于这种改善的细胞保留和存活，Grem 1-MSC可以持续分泌高浓度的Grem 1，Grem 1是一种新发现的促血管生成因子，可以通过激活磷酸肌醇3-激酶（PI 3 K）-AKT信号通路促进血管生成，从而改善缺血肢体的血液灌注和上级肢体挽救。本文开发的策略为缺血性疾病的有效的基于细胞的治疗提供了有希望的治疗选择。
Stem cell therapy is a promising strategy for the treatment of ischemic diseases such as critical limb ischemia (CLI). The major obstacle is the poor survival rate and low efficiency of the implanted stem cells. Biomimetic scaffolds such as injectable hydrogels have shown the ability to promote cell retention and survival. However, the local ischemic microenvironment especially the high level of reactive oxygen species (ROS) usually induces cell loss and dysfunction, thereby leading to unsatisfactory therapeutic outcomes. Herein, we developed a new injectable hybrid hydrogel composed of natural type I collagen and melanin nanoparticles (MeNPs) for the delivery of Gremlin1 (Grem1)-overexpressed mesenchymal stem cells (Grem1-MSCs) and CLI therapy. After local injection of this cell delivery system into the ischemic limbs of mice, the thermal-triggeredin situgelation of collagen could maintain Grem1-MSCs at the injection site and MeNPs entrapped in the hydrogel framework could modulate the ischemic microenvironment via scavenging ROS to promote the survival of implanted stem cells. With this improved cell retention and survival, Grem1-MSCs could constantly secrete high concentration of Grem1, a newly discovered proangiogenic factor that can promote angiogenesis by activating the phosphoinositide 3-kinase (PI3K)-AKT signaling pathway, thereby leading to improved blood perfusion in the ischemic limbs and superior limb salvage. The strategy developed herein offers a promising therapeutic option for the effective cell-based treatment of ischemic diseases.
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影响因子：
41.2
作者：
Khetan S;Guvendiren M;Legant WR;Cohen DM;Chen CS;Burdick JA
通讯作者：
Burdick JA
影响因子：
16.1
作者：
Cezar, Christine A.;Mooney, David J.
通讯作者：
Mooney, David J.
DOI：
10.1016/s0021-9258(17)37680-9
发表时间：
1994-02
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
C. Vlahos;W. Matter;K. Hui;R. F. Brown
通讯作者：
C. Vlahos;W. Matter;K. Hui;R. F. Brown
影响因子：
64.8
作者：
Robinton, Daisy A.;Daley, George Q.
通讯作者：
Daley, George Q.
影响因子：
20.3
作者：
Stabile, Helena;Mitola, Stefania;Presta, Marco
通讯作者：
Presta, Marco