A key feature of peripheral arterial disease (PAD) is damage to endothelial cells (ECs), resulting in lower limb pain and restricted blood flow. Recent preclinical studies demonstrate that the transplantation of ECs via direct injection into the affected limb can result in significantly improved blood circulation. Unfortunately, the clinical application of this therapy has been limited by low cell viability and poor cell function. To address these limitations we have developed an injectable, recombinant hydrogel, termed SHIELD (Shear-thinning Hydrogel for Injectable Encapsulation and Long-term Delivery) for cell transplantation. SHIELD provides mechanical protection from cell membrane damage during syringe flow. Additionally, secondary in situ crosslinking provides a reinforcing network to improve cell retention, thereby augmenting the therapeutic benefit of cell therapy. In this study, we demonstrate the improved acute viability of human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) following syringe injection delivery in SHIELD, compared to saline. Using a murine hind limb ischemia model of PAD, we demonstrate enhanced iPSC-EC retention in vivo and improved neovascularization of the ischemic limb based on arteriogenesis following transplantation of iPSC-ECs delivered in SHIELD.

中文翻译：

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蛋白质工程水凝胶可提高诱导的多能干细胞来源的内皮细胞的存活率，以治疗周围动脉疾病†

外周动脉疾病（PAD）的关键特征是对内皮细胞（EC）的损害，从而导致下肢疼痛和血流受限。最近的临床前研究表明，通过直接注射到患肢中的EC移植可以显着改善血液循环。不幸的是，这种疗法的临床应用受到细胞活力低和细胞功能差的限制。为了解决这些局限性，我们开发了一种可注射的重组水凝胶，称为SHIELD（用于注射封装和长期递送的剪切稀化水凝胶），用于细胞移植。SHIELD提供机械保护，防止注射器流动期间细胞膜受损。此外，原位继发交联提供增强网络以改善细胞保留，从而增强细胞疗法的治疗益处。在这项研究中，我们证明了与盐水相比，在SHIELD中注射注射后，人诱导的多能干细胞衍生的内皮细胞（iPSC-ECs）的急性生存能力得到了改善。使用PAD的鼠后肢缺血模型，我们证明了在iPSC-ECs在SHIELD中移植后，基于动脉生成的iPSC-EC在体内的保留增强，缺血肢体的新血管形成得到改善。