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脂肪来源的基质血管细胞的再生潜力和炎症诱导的分泌谱受供体变异性和既往乳腺癌诊断的影响。

Regenerative Potential and Inflammation-Induced Secretion Profile of Human Adipose-Derived Stromal Vascular Cells Are Influenced by Donor Variability and Prior Breast Cancer Diagnosis.

机构信息

Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, 175 Meeting Street, Box G-B397, Providence, RI, 02912, USA.

Department of Plastic and Reconstructive Surgery, Brown University, Providence, RI, USA.

出版信息

Stem Cell Rev Rep. 2018 Aug;14(4):546-557. doi: 10.1007/s12015-018-9813-1.

Abstract

Adipose tissue contains a heterogeneous population of stromal vascular fraction (SVF) cells that work synergistically with resident cell types to enhance tissue healing. Ease of access and processing paired with therapeutic promise make SVF cells an attractive option for autologous applications in regenerative medicine. However, inherent variability in SVF cell therapeutic potential from one patient to another hinders prognosis determination for any one person. This study investigated the regenerative properties and inflammation responses of thirteen, medically diverse human donors. Using non-expanded primary lipoaspirate samples, SVF cells were assessed for robustness of several parameters integral to tissue regeneration, including yield, viability, self-renewal capacity, proliferation, differentiation potential, and immunomodulatory cytokine secretion. Each parameter was selected either for its role in regenerative potential, defined here as the ability to heal tissues through stem cell repopulation and subsequent multipotent differentiation, or for its potential role in wound healing through trophic immunomodulatory activity. These data were then analyzed for consistent and predictable patterns between and across measurements, while also investigating the influence of the donors' relevant medical histories, particularly if the donor was in remission following breast cancer treatment. Analyses identified positive correlations among the expression of three cytokines: interleukin (IL)-6, IL-8, and monocyte chemoattractant protein (MCP)-1. The expression of these cytokines also positively related to self-renewal capacity. These results are potentially relevant for establishing expectations in both preclinical experiments and targeted clinical treatment strategies that use stem cells from patients with diverse medical histories.

摘要

脂肪组织包含异质的基质血管部分(SVF)细胞群体,它们与驻留细胞类型协同作用,以增强组织愈合。易于获取和处理以及治疗潜力使 SVF 细胞成为再生医学中自体应用的有吸引力的选择。然而,从一个患者到另一个患者的 SVF 细胞治疗潜力的固有变异性阻碍了任何一个人的预后确定。本研究调查了十三个医学多样化的供体的再生特性和炎症反应。使用未扩增的原发性脂肪抽吸样本,评估了 SVF 细胞在几个与组织再生相关的参数方面的稳健性,包括产量、活力、自我更新能力、增殖、分化潜力和免疫调节细胞因子分泌。每个参数都因其在再生潜力中的作用而被选择,这里定义为通过干细胞再增殖和随后的多能分化来治愈组织的能力,或者因其在通过营养免疫调节活性的伤口愈合中的潜在作用而被选择。然后,分析这些数据在测量之间和跨测量之间的一致和可预测模式,同时还研究了供体相关病史的影响,特别是如果供体在乳腺癌治疗后处于缓解期。分析确定了三种细胞因子(白细胞介素(IL)-6、IL-8 和单核细胞趋化蛋白 1(MCP)-1)表达之间的正相关。这些细胞因子的表达也与自我更新能力呈正相关。这些结果对于在使用来自具有不同病史的患者的干细胞的临床前实验和靶向临床治疗策略中建立预期可能具有重要意义。

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