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Controlled Release of Stem Cell Secretome Attenuates Inflammatory Response against Implanted Biomaterials.
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2020-05-18 , DOI: 10.1002/adhm.201901874 Mohammadreza Mohammadi 1, 2, 3 , Jennifer Cam Luong 2, 3 , Samuel Mathew Rodriguez 2 , Rui Cao 2, 3 , Ashlyn Elizabeth Wheeler 2 , Hien Lau 2 , Shiri Li 3 , Sepideh Kiani Shabestari 2 , Jean Paul Chadarevian 2 , Michael Alexander 3 , Paul de Vos 4 , Weian Zhao 2, 5, 6, 7, 8, 9 , Jonathan Robert Tod Lakey 2, 3
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2020-05-18 , DOI: 10.1002/adhm.201901874 Mohammadreza Mohammadi 1, 2, 3 , Jennifer Cam Luong 2, 3 , Samuel Mathew Rodriguez 2 , Rui Cao 2, 3 , Ashlyn Elizabeth Wheeler 2 , Hien Lau 2 , Shiri Li 3 , Sepideh Kiani Shabestari 2 , Jean Paul Chadarevian 2 , Michael Alexander 3 , Paul de Vos 4 , Weian Zhao 2, 5, 6, 7, 8, 9 , Jonathan Robert Tod Lakey 2, 3
Affiliation
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Inflammatory response against implanted biomaterials impairs their functional integration and induces medical complications in the host's body. To suppress such immune responses, one approach is the administration of multiple drugs to halt inflammatory pathways. This challenges patient's adherence and can cause additional complications such as infection. Alternatively, biologics that regulate multiple inflammatory pathways are attractive agents in addressing the implants immune complications. Secretome of mesenchymal stromal cells (MSCs) is a multipotent biologic, regulating the homeostasis of lymphocytes and leukocytes. Here, it is reported that alginate microcapsules loaded with processed conditioned media (pCM‐Alg) reduces the infiltration and/or expression of CD68+ macrophages likely through the controlled release of pCM. In vitro cultures revealed that alginate can dose dependently induce macrophages to secrete TNFα , IL‐6, IL‐1β , and GM‐CSF. Addition of pCM to the cultures attenuates the secretion of TNFα (p = 0.023) and IL‐6 (p < 0.0001) by alginate or lipopolysaccharide (LPS) stimulations. Mechanistically, pCM suppressed the Nfκ B pathway activation of macrophages in response to LPS (p < 0.0001) in vitro and cathepsin activity (p = 0.005) in response to alginate in vivo. These observations suggest the efficacy of using MSC‐derived secretome to prevent or delay the host rejection of implants.
中文翻译：
干细胞分泌组的受控释放可减弱针对植入生物材料的炎症反应。
针对植入生物材料的炎症反应会损害其功能整合并诱发宿主体内的医疗并发症。为了抑制这种免疫反应，一种方法是使用多种药物来阻止炎症途径。这对患者的依从性提出了挑战，并可能导致其他并发症，例如感染。另外，调节多种炎症途径的生物制剂是解决植入物免疫并发症的有吸引力的药物。间充质基质细胞 (MSC) 的分泌组是一种多能生物制剂，可调节淋巴细胞和白细胞的稳态。据报道，装载有加工条件培养基 (PCM-Alg) 的藻酸盐微胶囊可能通过控制 PCM 的释放来减少 CD68+ 巨噬细胞的浸润和/或表达。体外培养表明，海藻酸盐可以剂量依赖性地诱导巨噬细胞分泌 TNF α、IL-6、IL-1 β和 GM-CSF。在培养物中添加 PCM 可减弱藻酸盐或脂多糖 (LPS) 刺激产生的 TNF α ( p = 0.023) 和 IL-6 ( p < 0.0001)的分泌。从机制上讲，PCM 在体外抑制了巨噬细胞响应 LPS ( p < 0.0001) 时的Nf κ B 通路激活，并抑制了体内响应藻酸盐时的组织蛋白酶活性 ( p = 0.005)。这些观察结果表明，使用 MSC 衍生的分泌蛋白组可以有效预防或延迟植入物的宿主排斥。
更新日期：2020-06-24
中文翻译：
干细胞分泌组的受控释放可减弱针对植入生物材料的炎症反应。
针对植入生物材料的炎症反应会损害其功能整合并诱发宿主体内的医疗并发症。为了抑制这种免疫反应，一种方法是使用多种药物来阻止炎症途径。这对患者的依从性提出了挑战，并可能导致其他并发症，例如感染。另外，调节多种炎症途径的生物制剂是解决植入物免疫并发症的有吸引力的药物。间充质基质细胞 (MSC) 的分泌组是一种多能生物制剂，可调节淋巴细胞和白细胞的稳态。据报道，装载有加工条件培养基 (PCM-Alg) 的藻酸盐微胶囊可能通过控制 PCM 的释放来减少 CD68+ 巨噬细胞的浸润和/或表达。体外培养表明，海藻酸盐可以剂量依赖性地诱导巨噬细胞分泌 TNF α、IL-6、IL-1 β和 GM-CSF。在培养物中添加 PCM 可减弱藻酸盐或脂多糖 (LPS) 刺激产生的 TNF α ( p = 0.023) 和 IL-6 ( p < 0.0001)的分泌。从机制上讲，PCM 在体外抑制了巨噬细胞响应 LPS ( p < 0.0001) 时的Nf κ B 通路激活，并抑制了体内响应藻酸盐时的组织蛋白酶活性 ( p = 0.005)。这些观察结果表明，使用 MSC 衍生的分泌蛋白组可以有效预防或延迟植入物的宿主排斥。
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