Novel 3D Hematological Malignancy Organoid Platform to Study Disease Biology and Perform Chemosensitivity Assays for Patient-Specific Care
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Proportion of Live/Dead Myeloma Cells Using Bioprinting Technology
研究概览
简要总结
The objective of this project is to compare chemosensitivity between chemotherapy combinations in bone marrow aspirates using 3D organoid models. The investigators overarching hypothesis is that 3D organoids are ideal to test chemosensitivity in real time, to provide personalized medicine and guidance in the setting of relapsed hematologic malignancy and potentially other cancers.
详细描述
Optimize the novel 3D organoid technique already used to recreate hematologic tumors.
Optimize cell viability of hematologic cancer organoids to extend available time in culture by screening cell culture media cytokines and 3D extracellular matrix composition.
Evaluate hematologic tumor composition at different time points to confirm accurate tumor representation and identify genetic expression characteristics, unique mutations, and tumor-stroma interaction. These aspects of tumor interaction with its stromal microenviroment will provide critical knowledge to better understand its biology.
Evaluate chemosensitivity on patient derived 3D organoids. Using marrow aspirate from participants with hematologic malignancies, evaluate live/kill rates of hematologic cancer cells after being exposed to established regimen combinations after 24 and 36 hours of exposure at pre-determined concentrations.
Using participant samples, evaluate differences in gene expression and cell markers of the hematologic cancer cells that remained alive after chemotherapy exposure to better understand mechanisms of resistance.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with suspected or confirmed hematologic malignancy undergoing a bone marrow biopsy as part of their care.
- •The ability to understand and willingness to sign an IRB approved informed consent document.
排除标准
- 未提供
结局指标
主要结局
Proportion of Live/Dead Myeloma Cells Using Bioprinting Technology
时间窗: Up to 5 days
Bone marrow aspirates (around 3-7 ml) will be collected from participants with confirmed or suspected hematologic malignancy being evaluated with a bone marrow biopsy. The samples will be used to create 3D organoid constructs using a 3D bioprinting technology for automated organoid biofabrication using hyaluronic acid and gelatin-based hydrogel. The 3D organoid constructs allow extended time to simulate the protective environment cancer cells use to survive in bone marrow. Organoids will be assessed at 1, 3, and 5 days for viability of myeloma cells. Based on live/dead cells using fluorescent imaging, the hydrogel composition will be modified to allow the optimal media for cell survival ex vivo.
Tumor-Stroma Interactions
时间窗: Up to 5 days
To assess the interaction of myeloma cells with stromal cells in a 3D organoid model, plasma and myeloma cells will be labeled using differing colors of Vybrant Multicolor Cell Labeling Kit to allow visualization of the cells' nuceli. By confocal microscope, slides will be evaluated for Vybrant-labeled hematologic malignant cells or healthy plasma cells (different colors) to identify preferential cell interactions. These aspects of tumor interaction with its stromal microenvironment will provide critical knowledge to better understand its biology.
次要结局
- Number of Reduced Hematologic Malignant Myeloma Cells(Up to 3 days)
- Comparison of Cell Viability(24 and 36 hours)
- Organoid Responses Compared to Clinical Response(Up to 3 months)