Abstract：
Obesity is a global health challenge with limited therapeutic solutions. Here, we demonstrate the engineering of an energy-dissipating hybrid tissue (EDHT) in the body for weight control. EDHT is constructed by implanting a synthetic gel matrix comprising immunomodulatory signals and functional cells into the recipient mouse. The immunomodulatory signals induce the host stromal cells to create an immunosuppressive niche that protects the functional cells, which are overexpressing the uncoupling protein 1 (UCP1), from immune rejection. Consequently, these endogenous and exogenous cells co-develop a hybrid tissue that sustainedly produces UCP1 to accelerate the host\'s energy expenditure. Systematic experiments in high-fat diet (HFD) and transgenic (ob/ob) mice show that EDHT efficiently reduces body weight and relieves obesity-associated pathological conditions. Importantly, an 18-month observation for safety assessment excludes cell leakage from EDHT and reports no adverse physiological responses. Overall, EDHT demonstrates convincing efficacy and safety in controlling body weight.
摘要：
肥胖是一个全球性的健康挑战，治疗方案有限。这里,我们展示了体内用于控制体重的能量耗散混合组织（EDHT）的工程。通过将包含免疫调节信号和功能细胞的合成凝胶基质植入受体小鼠来构建EDHT。免疫调节信号诱导宿主基质细胞产生保护功能细胞的免疫抑制小生境，它们过表达解偶联蛋白1（UCP1），免疫排斥反应。因此,这些内源性和外源性细胞共同发育出一种混合组织，可持续产生UCP1以加速宿主的能量消耗。在高脂肪饮食(HFD)和转基因(ob/ob)小鼠中的系统实验表明,EDHT有效地降低体重并缓解与肥胖相关的病理状况。重要的是,一项为期18个月的安全性评估观察排除了EDHT的细胞渗漏,并报告无不良生理反应.总的来说,EDHT在控制体重方面表现出令人信服的功效和安全性。
