Enhancing the potency of mesenchymal stem cell therapies for kidney diseases using lab-on-a-particle technology

间充质干细胞（MSC）是一种有前途的治疗方式，用于许多其他疾病。 难治性疾病，主要是由于它们产生的旁分泌因子， 炎症、促进血管生成和抑制细胞凋亡。基于MSC的治疗正在 用于治疗多种肾脏和泌尿系统疾病，包括泌尿系统疾病 尿失禁、狼疮性肾炎和急性肾损伤转变为慢性肾病。 不幸的是，翻译研究的不同结果阻碍了大多数翻译研究的进展。 MSC疗法通过早期临床试验。也许翻译的最大障碍是 MSC分泌功能的固有异质性，已显示其基于 初始组织来源和用于细胞扩增的条件。目前，MSC 通过与细胞干细胞性相关但与细胞干细胞性无关的表面蛋白质来识别。 它们在治疗上重要的分泌功能，进一步加剧了临床上的差异。 翻译.技术丰富了我们对干细胞与肿瘤之间直接关系的理解， 分泌功能和再生潜力将证明是至关重要的标准化现有的 治疗和工程更有效的细胞疗法，为这些慢性和破坏性的 疾病虽然用于治疗效力的功能分析方法正逐渐被 集成到MSC开发管道中，目前还没有技术能够快速 基于治疗上重要的分泌的MSC，检测和富集单个MSC克隆 因素我们建议在粒子平台上开发一个新的实验室， 将单个MSC分离成具有结构化空腔的水凝胶微粒， 用于细胞粘附固体基质和用于均匀微滴形成的模板。这种方法 将能够同时分析细胞表面和分泌蛋白， 使用标准荧光激活细胞分选仪（FACS）对所需克隆进行分选。我们将评估 基于血管内皮生长因子的分泌选择克隆，并表征它们的 与急性肾损伤相关的组织再生相关的体外功能测定 肾病的转变。我们的新技术有望消除这一重大障碍， 功能性干细胞选择，以推动下一代MSC治疗肾脏和 泌尿系统疾病

Mesenchymal stem cells (MSCs) are a promising treatment modality for a multitude of otherwise intractable diseases, largely due to their production of paracrine factors which modulate inflammation, promote angiogenesis, and inhibit apoptosis. MSC-based therapies are being explored for the treatment of numerous kidney and urological diseases including urinary incontinence, lupus nephritis, and acute kidney injury transitioning to chronic kidney disease. Unfortunately, disparate results in translational studies have hindered the progression of most MSC therapies past early stage clinical trials. Perhaps the greatest barrier to translation is the inherent heterogeneity in secretory function of MSCs, which has been shown to vary based on both the initial tissue source and conditions used for cell expansion. Currently, MSCs are identified through surface proteins which correlate to cell stemness but are disconnected from their therapeutically important secretory functions, further exacerbating differences in clinical translation. Technologies enriching our understanding of the direct relation between stem cell secretory function and regenerative potential will prove crucial for the standardization of existing treatments and engineering more effective cell therapies for these chronic and devastating diseases. While functional profiling approaches for therapeutic potency are gradually being integrated into MSC development pipelines, there are currently no technologies capable of rapidly detecting and enriching individual MSC clones based on therapeutically important secreted factors. We propose the development of a novel lab on a particle platform, which allows the rapid isolation of individual MSCs into hydrogel microparticles with a structured cavity that provides a solid substrate for cell adhesion and a template for uniform microdroplet formation. This approach will enable profiling of both cell surface and secreted proteins simultaneously, and allow recovery of desired clones using standard fluorescence-activated cell sorters (FACS). We will evaluate the clones selected based on secretion of vascular endothelial growth factor and characterize their function in vitro assays relevant to tissue regeneration relevant to acute kidney injury to chronic kidney disease transition. Our new technology promises to remove this significant barrier in functional stem cell selection to drive the next-generation of MSC therapies for kidney and urologic diseases.