3D bioprinted white adipose model forin vitrostudy of cancer-associated cachexia induced adipose tissue remodeling.
3D bioprinted white adipose model forin vitrostudy of cancer-associated cachexia induced adipose tissue remodeling.
复制标题
3D生物打印白色脂肪模型用于癌症相关恶病质诱导脂肪组织重塑的体外研究
DOI：
10.1088/1758-5090/ac6c4b
复制
发表时间：
2022-05-26
期刊：
影响因子：
9
通讯作者：
Duan, Bin
中科院分区：
文献类型：
--
作者：
Xue, Wen;Yu, Seok-Yeong;Kuss, Mitchell;Kong, Yunfan;Shi, Wen;Chung, Soonkyu;Kim, So-Youn;Duan, Bin
癌症相关性恶病质(CAC)是一种复杂的代谢和行为综合征，具有多种表现，包括全身炎症、体重减轻和脂肪分解。它影响患者的生活质量，是20%-30%的癌症患者死亡的直接原因。脂肪丢失和脂肪组织重塑的严重程度与患者的生存结局呈负相关。为了解决脂肪丢失的机制并设计预防这一过程的潜在方法，通过白色脂肪组织模型了解CAC的病理生理学将是至关重要的。本研究建立了一种基于三维生物打印的工程化人类白色脂肪组织(EWAT)模型，并用胰腺癌细胞条件培养液(CM)诱导，以模拟CAC的体外状态。我们发现，CM诱导显著增加了细胞外基质(ECM)的脂解和积聚。进一步对3D eWAT进行血管化，以研究血管化对脂解和CAC进展的影响，这在很大程度上是未知的。结果表明，CM诱导可促进血管eWATs的血管生成，与eWATs相比，veWATs的甘油释放减少，而UCP1的表达增加。从CM中检测到许多独特的炎性细胞因子(IL-8、CXCL-1、GM-CSF等)，并被认为与eWAT脂解、UCP1上调和ECM的发展有关。作为对CM诱导的反应，eWATs还分泌与癌症转移能力、肌肉萎缩和血管形成有关的炎性脂肪因子(NGAL、CD54、IGFBP-2等)。我们的工作表明，eWAT是研究恶病质脂肪丢失和伴随的脂肪组织重塑的可靠模型。因此，它是未来研究探索CAC生理学和开发潜在治疗方法的有用工具。
Cancer-associated cachexia (CAC) is a complex metabolic and behavioral syndrome with multiple manifestations that involve systemic inflammation, weight loss, and adipose lipolysis. It impacts the quality of life of patients and is the direct cause of death in 20–30% of cancer patients. The severity of fat loss and adipose tissue remodeling negatively correlate with patients’ survival outcomes. To address the mechanism of fat loss and design potential approaches to prevent the process, it will be essential to understand CAC pathophysiology through white adipose tissue models. In the present study, an engineered human white adipose tissue (eWAT) model based on three-dimensional (3D) bioprinting was developed and induced with pancreatic cancer cell-conditioned medium (CM) to mimic the status of CAC in vitro. We found that the CM induction significantly increased the lipolysis and accumulation of the extracellular matrix (ECM). The 3D eWATs were further vascularized to study the influence of vascularization on lipolysis and CAC progression, which was largely unknown. Results demonstrated that CM induction improved the angiogenesis of vascularized eWATs (veWATs), and veWATs demonstrated decreased glycerol release but increased UCP1 expression, compared to eWATs. Many unique inflammatory cytokines (IL-8, CXCL-1, GM-CSF, etc) from the CM were detected and supposed to contribute to eWAT lipolysis, UCP1 up-regulation, and ECM development. In response to CM induction, eWATs also secreted inflammatory adipokines related to the metastatic ability of cancer, muscle atrophy, and vascularization (NGAL, CD54, IGFBP-2, etc). Our work demonstrated that the eWAT is a robust model for studying cachectic fat loss and the accompanying remodeling of adipose tissue. It is therefore a useful tool for future research exploring CAC physiologies and developing potential therapies.
登录
查看更多内容
影响因子：
3
作者：
Choi, Jennifer H.;Gimble, Jeffrey M.;Kaplan, David L.
通讯作者：
Kaplan, David L.
影响因子：
56.9
作者：
Das, Suman K.;Eder, Sandra;Hoefler, Gerald
通讯作者：
Hoefler, Gerald
Lipocalin-2/ngal作为炎症和代谢疾病的生物标志物的潜力。
DOI：
10.3109/1354750x.2015.1123354
发表时间：
2015
期刊：
Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals
影响因子：
--
作者：
Abella V;Scotece M;Conde J;Gómez R;Lois A;Pino J;Gómez-Reino JJ;Lago F;Mobasheri A;Gualillo O
通讯作者：
Gualillo O
影响因子：
7.4
作者：
Aguirre GA;De Ita JR;de la Garza RG;Castilla-Cortazar I
通讯作者：
Castilla-Cortazar I
影响因子：
3.7
作者：
Delort L;Lequeux C;Dubois V;Dubouloz A;Billard H;Mojallal A;Damour O;Vasson MP;Caldefie-Chézet F
通讯作者：
Caldefie-Chézet F