Nanotracer Development to Track Stem Cell Therapy

追踪干细胞治疗的纳米示踪剂开发

• 批准号: 9922903
• 负责人: Laura J Suggs
• 金额: $ 41.84万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9922903
• 关键词: 3-Dimensional; Autologous; Biological Models; Blood flow; Bone Marrow; Cardiovascular Diseases; Cell Cycle Kinetics; Cell Death; Cell Survival; Cells; Clinical Trials; Data; Data Reporting; Detection; Development; Event; Gastrocnemius Muscle; Goals; Gold; Hindlimb; Histologic; Hydrogels; Hypoxia; Image; Imaging Techniques; Immune response; In Situ; Inductively Coupled Plasma Mass Spectrometry; Infiltration; Inflammatory Infiltrate; Injections; Injury; Ischemia; Label; Lead; Limb Salvage; Limb structure; Lower Extremity; Lysine; Measurement; Measures; Mediating; Mesenchymal Stem Cells; Methods; Modeling; Modification; Mus; Muscle; Muscle Cells; Muscle function; Optics; Outcome; Patients; Peripheral arterial disease; Phenotype; Physiological; Property; Rattus; Recovery; Recovery of Function; Reperfusion Therapy; Resolution; Role; Safety; Sensitivity and Specificity; Shapes; Site; System; Therapeutic; Time; Tissue imaging; Ultrasonography; Visualization; Work; absorption; arginase; base; biomaterial compatibility; cellular imaging; clinical development; clinical efficacy; clinically translatable; critical limb Ischemia; early phase clinical trial; high resolution imaging; imaging study; implantation; improved; improved functioning; in vivo; interdisciplinary approach; ischemic injury; macrophage; mouse model; nanoparticle; nanoshell; photoacoustic imaging; plasmonics; polyhexamethylene biguanide; quantitative imaging; recruit; regenerative; repaired; response; stem cell technology; stem cell therapy; stem cells; surface coating; therapy outcome; tissue regeneration

Project Summary Peripheral artery disease (PAD) is a form of cardiovascular disease that can reduce blood flow in the lower limbs ultimately resulting in the potential for loss of limb. Early clinical trials in patients with PAD resulting in critical limb ischemia have demonstrated the safety of autologous stem cell therapies with modest improvements in reperfusion and limb salvage. While stem cell therapies may therefore represent a realistic alternative to conventional revascularization therapies, a number of challenges remain which limit large-scale clinical trials and widespread use. Outcomes with respect to clinical efficacy have been less than ideal and are largely attributed to the well-documented cell loss following delivery. The overwhelming majority (>90 %) of cells do not survive implantation after 1-2 weeks. We have described that a degradable hydrogel matrix can improve stem cell-mediated muscle function recovery following ischemic injury. Our data suggested that one mechanism for improved recovery was the increased number of cells that were maintained at the site of injury and their beneficial effects on the host response. Central to our understanding is the necessity of being able to track stem cells and the infiltrating inflammatory cells, particularly macrophages. Major challenges to the development of clinically applied stem cell therapy remains the lack of technologies for stem cell tracking, methods for the improvement of cell viability and strategies to understand the stem cell-mediated host response. Therefore, the overall goal of the current proposal is to understand the role of delivered stem cells and the mechanisms of repair in vivo using nanotracer-enhanced, high-resolution combined ultrasound and photoacoustic (US/PA) imaging. A secondary goal is to be able to quantify the role of recruited macrophages in a model system in which we are able to correlate imaging quantification with quantitative measures of muscle function. We propose here to utilize plasmonic gold nanoshells as nanotracers, due to their excellent biocompatibility, as well as tunable, strong optical absorption properties. In contrast with other imaging techniques, combined US/PA imaging can visualize and quantify cell delivery and function over a broad range of timescales, spatial resolutions and imaging depths. High-resolution imaging of tissues is possible as well as visualization in 3D. The combination of nanotracers with US/PA imaging results in a unique approach that will allow us to answer fundamental questions regarding MSC involvement in muscle repair as well as validate a clinically translatable solution for tissue regeneration. We propose to develop this single system in a mouse model of hindlimb ischemia in which we are able to quantify muscle function, thereby allowing correlation with tissue regeneration.

项目总结

项目成果

Assessing the range of enzymatic and oxidative tunability for biosensor design.

• DOI: 10.1039/c9tb02666e
• 发表时间: 2020-03
• 期刊: Journal of materials chemistry. B
• 作者: H. Schunk;Derek S. Hernandez;M. J. Austin;Kabir S. Dhada;A. Rosales;L. Suggs

A Dual Gold Nanoparticle System for Mesenchymal Stem Cell Tracking.

• DOI: 10.1039/c4tb00975d
• 发表时间: 2014-12-14
• 期刊: Journal of materials chemistry. B
• 作者: Ricles LM;Nam SY;Treviño EA;Emelianov SY;Suggs LJ
• 通讯作者: Suggs LJ

Multifunctional nanoscale strategies for enhancing and monitoring blood vessel regeneration.

• DOI: 10.1016/j.nantod.2012.10.007
• 发表时间: 2012-12
• 期刊: Nano today
• 影响因子: 17.4
• 作者: Chung E;Ricles LM;Stowers RS;Nam SY;Emelianov SY;Suggs LJ
• 通讯作者: Suggs LJ

Controlled release of IGF-I from a biodegradable matrix improves functional recovery of skeletal muscle from ischemia/reperfusion.

• DOI: 10.1002/bit.24382
• 发表时间: 2012-04
• 期刊: Biotechnology and bioengineering
• 影响因子: 3.8
• 作者: Hammers DW;Sarathy A;Pham CB;Drinnan CT;Farrar RP;Suggs LJ
• 通讯作者: Suggs LJ

Fibrin-based 3D matrices induce angiogenic behavior of adipose-derived stem cells.

• DOI: 10.1016/j.actbio.2015.01.012
• 发表时间: 2015-04
• 期刊: ACTA BIOMATERIALIA
• 影响因子: 9.7
• 作者: Chung, Eunna;Rytlewski, Julie A.;Merchant, Arjun G.;Dhada, Kabir S.;Lewis, Evan W.;Suggs, Laura J.
• 通讯作者: Suggs, Laura J.