Ultrasound-guided photoacoustic imaging and tracking of stem cells in the spinal cord

超声引导光声成像和脊髓干细胞追踪

• 批准号: 9978212
• 负责人: STANISLAV Y EMELIANOV
• 金额: $ 43.4万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2022-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9978212
• 关键词: 3-Dimensional; Abbreviations; Address; Amyotrophic Lateral Sclerosis; Apoptosis; Apoptotic; Area; Autopsy; BODIPY; Biological; CASP3 gene; Cell Count; Cell Survival; Cell Transplantation; Cells; Clinical; Clinical Engineering; Clinical Trials; Contrast Media; Development; Disadvantaged; Disease; Engraftment; Feedback; Foundations; Glossary; Goals; Gold; Histologic; Histology; Imaging Techniques; Immune; Implant; In Vitro; Injections; Ionizing radiation; Label; Location; Magnetic Resonance Imaging; Mesenchymal Stem Cells; Monitor; Operative Surgical Procedures; Optics; Patients; Penetration; Positron-Emission Tomography; Postoperative Period; Procedures; Protocols documentation; Rattus; Research; Research Personnel; Risk; Rodent; Scientist; Signal Transduction; Spinal Cord; Spinal Cord Diseases; Spinal cord injury; Stem cell transplant; System; Techniques; Technology; Therapeutic; Time; Tissue Sample; Tissues; Translations; Transplantation; Treatment Efficacy; Ultrasonography; Work; X-Ray Computed Tomography; base; clinical imaging; clinically relevant; cost effective; effective therapy; high risk; image guided; imaging approach; imaging platform; imaging study; imaging system; in vivo; in vivo imaging; migration; minimal risk; nanorod; novel; photoacoustic imaging; portability; post-transplant; preclinical study; programs; real-time images; sensor; serial imaging; spinal cord imaging; stem cell fate; stem cell therapy; stem cells; success

ABSTRACT Stem cells, including mesenchymal stem cells (MSCs) have proven to be an exciting and promising thera- peutic for the treatment of numerous diseases and disorders of the spinal cord, such as spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS). Positive results in preclinical studies have led to an increase in transla- tion of stem cell therapies. However, upon reaching clinical trials, many stem cell therapeutics fail. In search for answers, the clinicians and researchers are missing critical information; the fate of the cells once implanted. Therefore, there is a definite and urgent clinical need for a technique that is capable of accurate real-time guid- ance of quantitative stem cell delivery to target areas, noninvasive longitudinal in vivo tracking of stem cell loca- tion, and assessment of stem cell viability over time after the delivery. This project is based on a hypothesis that stem cells can be effectively labeled with a photoacoustic imaging contrast agent and a photoacoustic apoptosis sensor to visualize cell localization and ascertain their viability, respectively; and ultrasound-guided photoacous- tic (USPA) imaging system and approach can be developed for longitudinal, quantitative, and noninvasive track- ing of double-labeled stem cells and their fate in vivo. The overall goal of this research program is to develop a novel cell labeling system and corresponding USPA imaging approach allowing real time image guidance for precise and accurate injection of the stem cells, and longitudinal tracking both the location and viability of stem cells in vivo in the spinal cord. First, a PA sensitive tracker will be developed, which will allow for real time feedback on the location of the stem cells during and immediately after injection, as well as post-operative tracking the location of the transplanted cells over time. Second, a PA sensor of apoptosis will be developed. This sensor will provide a unique PA signal in cells which are undergoing apoptosis, allowing us to ascertain the cells viability. The combination of both PA tracker and apoptotic sensor to double label stem cells is critical for real time imaged guided delivery of cells, and tracking viable and apoptotic cells longitudinally in vivo. The USPA imaging double-labeled cells will provide highly valu- able information of the fate of stem cells in vivo, which can be used to refine and advance the field of stem cell transplantation in the spinal cord. If successful, this work will lay foundation for in vivo real-time intra-operative and then longitudinal USPA imaging of transplanted cells within the spinal cord – the technology needed by both scientists and clinicians.

抽象的 事实证明，包括间充质干细胞（MSC）在内的干细胞是令人兴奋且有希望的thera- 治疗脊髓的多种疾病和疾病的治疗，例如脊髓损伤（SCI） 和肌萎缩性侧索硬化症（ALS）。临床前研究的积极结果导致翻译的增加 干细胞疗法的影响。但是，在进行临床试验后，许多干细胞疗法失败。搜索 答案，临床医生和研究人员缺少关键信息。细胞的命运曾经植入。 因此，对能够准确实时指南的技术有明确且紧急的临床需求 定量干细胞向目标区域的递送，无创纵向在体内跟踪干细胞位置 - 分娩后的时间和评估干细胞活力的评估。该项目基于一个假设 干细胞可以用光声成像对比剂和光声凋亡有效地标记 传感器可视化细胞定位并确定其生存能力；和超声引导的光人 - 可以为纵向，定量和无创轨迹开发TIC（USPA）成像系统和方法 双标记的干细胞及其在体内的命运。 该研究计划的总体目标是开发一个新型的细胞标签系统和相应的USPA 成像方法允许实时图像指导，以精确和准确注射干细胞，以及 纵向跟踪干细胞体内脊髓中干细胞的位置和活力。首先，PA敏感 将开发跟踪器，这将允许对干细胞的位置进行实时反馈和 注射后，以及术后跟踪移植细胞的位置，随着时间的流逝。 其次，将开发出凋亡的PA传感器。该传感器将在单元格中提供独特的PA信号 正在凋亡，使我们能够确定细胞的生存能力。 PA跟踪器和 凋亡传感器以双重标记干细胞对于实时成像的引导输送和跟踪至关重要 可行和凋亡细胞在体内纵向。 USPA成像双标记的单元将提供高价值 - 体内干细胞命运的能力信息，可用于完善和推进干细胞领域 在脊髓中移植。如果成功，这项工作将为体内实时术中奠定基础 然后，脊髓中移植细胞的纵向USPA成像 - 两者都需要的技术 科学家和临床医生。