3D Bioprinted lung cancer models for drug screening

我们已经建立了使用原代肺内皮细胞、周细胞和成纤维细胞对肺血管基底层组织进行生物打印的方案。免疫组织化学和荧光显微镜观察血管生成和血管生成。我们还开发了用慢病毒转导的荧光蛋白标记癌细胞的方案，并监测了一组不同转移来源的膀胱癌细胞在组织中的肿瘤形成。我们还通过在带血管的肺基底部组织上分层原代间皮细胞来建立肺胸膜模型，以在胸膜组织中建立间皮瘤模型。最后，我们还建立了在气液界面(ALI)对小气道上皮细胞(SAEC)进行分层和分化的方案，并添加了荧光标记的NSCLC肿瘤细胞，并展示了肺上皮ALI组织上肿瘤的形成。目前，我们正在探索NSCLC癌细胞在ALI处具有分化SAEC层的整个血管肺组织中的生长情况。一旦这项工作完成，我们将实施NCATS肿瘤学集合的HTS，在肺组织模型中寻找防止NSCLC肿瘤生长的化合物。

We have established protocols for the bioprinting of a lung vascularized basal tissue using primary lung endothelial cells, pericytes and fibroblasts. IHC and fluorescence microcopy was used to establish vasculogenesis and angiogenesis. We also developed protocols for the labeling of cancer cells with lentivirus transduced florescence proteins and monitor tumor formation in the tissue for a set of bladder cancer cells with different metastatic origin. We are also establishing a model of the lung pleural by layering primary mesothelial cells on top of the vascularized lung base tissue to create model of mesothelioma in a pleura tissue. Finally, we have also established protocols to layer and differentiate small airway epithelial cells (SAEC) at the air-liquid interface (ALI) and have added fluorescently labeled NSCLC tumor cells and demonstrated formation of tumors on the lung epithelial ALI tissue. Currently, we are exploring the growth of NSCLC cancer cells in the the whole vascularized lung tissue with a differentiated SAEC layer at the ALI. Once this work is completed, we will implement the HTS of the NCATS oncology collection looking for compounds that prevent NSCLC tumor growth in a lung tissue model.