title: Real-time tracking of adipose tissue-derived stem cells with injectable scaffolds in the infarcted heart.
abstract: Adipose tissue-derived stem cells (ADSCs) has shown promise in the emerging field of regenerative medicine. Many studies have highlighted the importance of coadministering a "scaffold" for increasing intramyocardial retention of stem cells. In this work, an optimized method was developed for efficient transduction of ADSCs with a lentiviral vector carrying a triple-fusion reporter gene that consists of firefly luciferase, monomeric red fluorescence protein, and truncated thymidine kinase (fluc-mrfp-ttk). The transduced ADSCs were assessed on biological performance and transplanted into infarcted heart with fibrin scaffolds. In vivo cell retention was tracked by bioluminescence imaging (BLI) and micro positron emission tomography/computed tomography (PET/CT) imaging. Histological assessment was performed for regeneration potentials. The results showed that lentiviral transduction did not influence cell functions. In vitro imaging analysis showed a robust linear correlation between cell numbers and BLI signals (R (2) = 0.99) as well as between cell numbers and radiotracer uptakes (R (2) = 0.98). Transduced ADSCs were visualized in the heart under both BLI and PET/CT imaging, contributing to cardiomyocyte regeneration and angiogenesis in the implanted areas. Compared with BLI monitoring, PET/CT data provided precise localization for cell retention. Thus, a combination of imaging modalities can assist in reliable and efficient monitoring of transplanted cells, holding great potential for the transplantation of injectable scaffolds encapsulating stem cells in treating heart disease.
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, People's Republic of China.
authors.forename: Jun-jie
authors.initials: JJ
authors.lastname: Yang
authors.forename: Zhi-qiang
authors.initials: ZQ
authors.lastname: Liu
authors.forename: Jin-ming
authors.initials: JM
authors.lastname: Zhang
authors.forename: Hai-bin
authors.initials: HB
authors.lastname: Wang
authors.forename: Shun-yin
authors.initials: SY
authors.lastname: Hu
authors.forename: Jian-feng
authors.initials: JF
authors.lastname: Liu
authors.forename: Chang-yong
authors.initials: CY
authors.lastname: Wang
authors.forename: Yun-dai
authors.initials: YD
authors.lastname: Chen
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D058948:Cell Tracking / Q000379:methods; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D017930:Genes, Reporter; D005822:Genetic Vectors; D016086:Lentivirus / Q000235:genetics; D049409:Luciferases, Firefly / Q000096:biosynthesis / Q000235:genetics; D008163:Luminescent Measurements; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D064847:Multimodal Imaging; D039902:Multipotent Stem Cells / Q000378:metabolism / Q000637:transplantation*; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D009206:Myocardium / Q000473:pathology*; D018919:Neovascularization, Physiologic; D010641:Phenotype; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D013937:Thymidine Kinase / Q000096:biosynthesis / Q000235:genetics; D013997:Time Factors; D054457:Tissue Scaffolds; D014161:Transduction, Genetic; D014162:Transfection; D055114:X-Ray Microtomography; D000097573:Red Fluorescent Protein
chemical_list: D015415:Biomarkers; D049409:Luciferases, Firefly; D008164:Luminescent Proteins; D013937:Thymidine Kinase; D000097573:Red Fluorescent Protein