Trimodal Vitality Imaging of Neural Progenitor Cells in the Spinal Cord

脊髓神经祖细胞的三模态活力成像

基本信息

批准号：
10611905
负责人：
STANISLAV Y EMELIANOV
金额：
$ 62.49万
依托单位：
GEORGIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10611905
关键词：
3-Dimensional Abbreviations Address Affect Amyotrophic Lateral Sclerosis Anatomy Apoptosis Apoptotic Area Autopsy Behavior Biological CASP3 gene Cell Survival Cell Therapy Cell Transplantation Cells Clinic Clinical Clinical Protocols Clinical Trials Contrast Media Cytosol Data Development Disease Dyes Engineering Engraftment Excision Failure Family suidae Fiber Optics Foundations Future Glossary Head Histologic Histology Image Imaging Techniques Imaging technology Implant In Vitro Injections Label Laminectomy Lasers Light Location Magnetic Resonance Imaging Magnetic nanoparticles Methods Modality Monitor Nature Needles Penetration Performance Physiologic pulse Postoperative Period Procedures Property Protocols documentation Quality of life Rattus Reporter Risk Rodent Sampling Scanning Scientist Signal Transduction Source Spinal Cord Spinal Cord Diseases Spinal cord injury Stem cell transplant System Techniques Testing Therapeutic Time Tissue Model Tissues Toxic effect Translations Transplantation Ultrasonography Visualization Work bone cell behavior clinical imaging clinical translation cost effective effective therapy image guided imaging modality imaging platform imaging system implantation improved in vivo in vivo imaging migration multimodality nerve stem cell neuroimaging neuroprotection non-invasive imaging novel optical fiber photoacoustic imaging portability post-transplant pre-clinical preclinical study real-time images spinal cord imaging stem cell delivery stem cell therapy technology platform tool ultrasound

项目摘要

ABSTRACT Spinal cord diseases and disorders such as spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS) are debilitating, often resulting in loss of mobility and decreased quality of life for those affected. One promising treatment involves the transplantation of neural progenitor cells (NPC) into the spinal cord, which has been shown to have neuroprotective properties. However, most NPC-based therapies fail after reaching clinical trials, and without a method to monitor the injected cells and viability, locating injected NPCs is limited to postmortem histology. The ability to track and assess the viability of transplanted cells could be crucial in understanding whether the failure is technical or biological in nature, such as whether the injected cells were delivered to and remain at the correct location or survived transplantation. We propose the development of multi-modal contrast agents and a clinical ultrasound and photoacoustic (US/PA) imaging system for image guided delivery of trans- planted cells and longitudinal monitoring. Together with clinical magnetic resonance imaging (MRI), the use of US/PA imaging can allow for pre-, intra- and post-operative visualization of the cells. The MRI and US imaging modalities are well established in the clinic, and PA can be easily integrated with existing clinical US imaging systems. We hypothesize that visualizing the location and viability of injected neural progenitor cells obtained through the labeling of NPCs with contrast agents will allow for better understanding of transplanted cell behavior and improved translation of cell based therapies. Two contrast agents will be developed: photo-magnetic nano- particles, which will allow for photoacoustic and MRI tracking, and a dye-based apoptosis reporter, which will provide photoacoustic contrast upon apoptotic activity. These will be delivered to the cytosol of the neural pro- genitor cells and assessed for labeling efficiency and toxicity. Once optimized, labeled NPCs in different ratios of live to dead will be injected into the spinal cords of rats to assess the feasibility of distinguishing live and dead cells in vivo. After injection, the NPCs will be monitored longitudinally using trimodal US/PA/MR imaging. After validating the performance of the contrast agents in vivo, a clinical US/PA imaging system will be developed to demonstrate real-time image guided-delivery, US/PA/MRI longitudinal tracking, and PA viability assessment of the labeled cells. The ability to monitor the transplanted cells at every point during and after the procedure will allow for more accurate delivery of the cells and could elucidate common issues and behaviors of injected NPCs that could lead to therapeutic improvements. Furthermore, if successful, it will validate both the contrast agents and US/PA as a valuable tool for tracking and monitoring cell-based therapies to improve clinical translation.

抽象的脊髓疾病和疾病，例如脊髓损伤（SCI）和肌萎缩性外侧硬化症（ALS）使人衰弱，通常导致流动性丧失和受影响者的生活质量下降。一个有希望的治疗涉及将神经祖细胞（NPC）移植到脊髓中，显示具有神经保护特性。但是，大多数基于NPC的疗法在进行临床试验后失败，并且没有监视注入的单元和生存能力的方法，定位的NPC仅限于验尸组织学。跟踪和评估移植细胞的生存能力的能力对于理解可能至关重要失败是技术性的还是生物学本质上的，例如注射细胞是否已输送到和保持在正确的位置或幸存的移植。我们提出了多模式对比的发展代理和临床超声和光声（US/PA）成像系统，用于图像指导的转移传递种植的细胞和纵向监测。连同临床磁共振成像（MRI）一起使用 US/PA成像可以允许细胞前，内和术后可视化。 MRI和我们的成像在诊所中建立了良好的模式，并且PA可以轻松地与现有的临床美国成像集成在一起系统。我们假设可视化注射神经祖细胞的位置和生存能力通过与对比剂的NPC的标记，可以更好地理解移植的细胞行为并改善了基于细胞的疗法的翻译。将开发两种对比剂：照片磁纳米 - 颗粒将允许光声和MRI跟踪，以及基于染料的凋亡报告基因在凋亡活性上提供光声对比。这些将交付给神经促性的细胞质生长细胞并评估标记效率和毒性。一旦优化，以不同比率标记为NPC 活到死的生命将被注入大鼠的脊髓中，以评估区分生命和死亡的可行性细胞体内。注射后，将使用Trimodal US/PA/MR成像对NPC进行纵向监测。后验证体内对比剂的性能，将开发出临床美国/PA成像系统展示实时图像指导性传递，US/PA/MRI纵向跟踪和PA生存能力评估标记的细胞。在过程中和之后的每个点监视移植的单元的能力将允许更准确地传递细胞，并可以阐明注射NPC的常见问题和行为这可能会导致治疗性改善。此外，如果成功，它将验证两种对比剂以及美国/PA作为跟踪和监测基于细胞的疗法以改善临床翻译的宝贵工具。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

In Vivo Photoacoustic Monitoring of Stem Cell Location and Apoptosis with Caspase-3-Responsive Nanosensors.

DOI：
10.1021/acsnano.3c04161
发表时间：
2023-09-26
期刊：
ACS NANO
影响因子：
17.1
作者：
Jhunjhunwala, Anamik;Kim, Jinhwan;Kubelick, Kelsey P.;Ethier, C. Ross;Emelianov, Stanislav Y.
通讯作者：
Emelianov, Stanislav Y.

Hyper-Branched Gold Nanoconstructs for Photoacoustic Imaging in the Near-Infrared Optical Window.

DOI：
10.1021/acs.nanolett.3c02177
发表时间：
2023-10-25
期刊：
NANO LETTERS
影响因子：
10.8
作者：
Kim, Myeongsoo;Vanderlaan, Don;Lee, Jeungyoon;Choe, Ayoung;Kubelick, Kelsey P.;Kim, Jinhwan;Emelianov, Stanislav Y.
通讯作者：
Emelianov, Stanislav Y.

A Trimodal Ultrasound, Photoacoustic and Magnetic Resonance Imaging Approach for Longitudinal Post-operative Monitoring of Stem Cells in the Spinal Cord.

DOI：
10.1016/j.ultrasmedbio.2020.08.026
发表时间：
2020-12
期刊：
Ultrasound in medicine & biology
影响因子：
2.9
作者：
Kubelick KP;Emelianov SY
通讯作者：
Emelianov SY

In vivo shear wave elasticity imaging for assessment of diaphragm function in muscular dystrophy.

体内剪切波弹性成像用于评估肌营养不良症的膈肌功能。

DOI：
10.1016/j.actbio.2023.07.009
发表时间：
2023
期刊：
Acta biomaterialia
影响因子：
9.7
作者：
Lee,Jeehyun;Myrie,NiaO;Jeong,Gun-Jae;Han,WoojinM;Jang,YoungC;García,AndrésJ;Emelianov,Stanislav
通讯作者：
Emelianov,Stanislav

Gold nanoparticles conjugated with DNA aptamer for photoacoustic detection of human matrix metalloproteinase-9.