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.

摘要 干细胞，包括间充质干细胞（MSC）已被证明是一个令人兴奋的和有前途的治疗， 用于治疗许多脊髓疾病和障碍，如脊髓损伤（SCI） 和肌萎缩侧索硬化症（ALS）。临床前研究的积极结果导致transla增加， 干细胞治疗的作用然而，在进入临床试验后，许多干细胞疗法失败了。在寻找 然而，临床医生和研究人员缺少关键信息，即细胞一旦植入后的命运。 因此，有一个明确的和迫切的临床需要的技术，是能够准确的实时指导， 定量干细胞递送到靶区域的机会，干细胞定位的非侵入性纵向体内跟踪， 以及在递送后随时间推移评估干细胞活力。这个项目是基于一个假设， 干细胞可以用光声成像造影剂和光声细胞凋亡有效地标记 传感器，以可视化细胞定位和确定其活力，分别;和超声引导的光声， tic（USPA）成像系统和方法可以开发用于纵向，定量和非侵入性跟踪， 双标记干细胞及其在体内的命运。 本研究计划的总体目标是开发一种新的细胞标记系统和相应的USPA 成像方法，其允许真实的时间图像引导以精确和准确地注射干细胞，以及 纵向追踪脊髓中干细胞的体内位置和活力。首先，PA敏感 将开发跟踪器，这将允许真实的时间反馈的干细胞的位置， 注射后立即进行，以及术后随时间跟踪移植细胞的位置。 第二，将开发细胞凋亡的PA传感器。该传感器将在细胞中提供独特的PA信号， 正在经历凋亡，使我们能够确定细胞的活力。PA跟踪器和 双标记干细胞的凋亡传感器对于细胞的真实的实时成像引导递送和跟踪是至关重要的 活细胞和凋亡细胞纵向体内。USPA成像双标记细胞将提供高价值， 干细胞在体内的命运的有用信息，可用于完善和推进干细胞领域 脊髓移植如果成功的话，这将为在体实时术中检测奠定基础 然后对脊髓内的移植细胞进行纵向USPA成像-这两种技术都需要 科学家和临床医生。