دورية أكاديمية

Therapeutic potential of clinical-grade human induced pluripotent stem cell-derived cardiac tissues.

التفاصيل البيبلوغرافية
العنوان: Therapeutic potential of clinical-grade human induced pluripotent stem cell-derived cardiac tissues.
المؤلفون: Osada H; Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.; Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan., Kawatou M; Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.; Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan., Fujita D; iHeart Japan Corporation, Kyoto, Japan., Tabata Y; Department of Biomaterials, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan., Minatoya K; Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Yamashita JK; Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan., Masumoto H; Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.; Clinical Translational Research Program, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.
المصدر: JTCVS open [JTCVS Open] 2021 Oct 01; Vol. 8, pp. 359-374. Date of Electronic Publication: 2021 Oct 01 (Print Publication: 2021).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Ltd Country of Publication: Netherlands NLM ID: 101768541 Publication Model: eCollection Cited Medium: Internet ISSN: 2666-2736 (Electronic) Linking ISSN: 26662736 NLM ISO Abbreviation: JTCVS Open Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Amsterdam, The Netherlands] : Elsevier Ltd., [2020]-
مستخلص: Objectives: To establish a protocol to prepare and transplant clinical-grade human induced pluripotent stem cell (hiPSC)-derived cardiac tissues (HiCTs) and to evaluate the therapeutic potential in an animal myocardial infarction (MI) model.
Methods: We simultaneously differentiated clinical-grade hiPSCs into cardiovascular cell lineages with or without the administration of canonical Wnt inhibitors, generated 5- layer cell sheets with insertion of gelatin hydrogel microspheres (GHMs) (HiCTs), and transplanted them onto an athymic rat MI model. Cardiac function was evaluated by echocardiography and cardiac magnetic resonance imaging and compared with that in animals with sham and transplantation of 5-layer cell sheets without GHMs. Graft survival, ventricular remodeling, and neovascularization were evaluated histopathologically.
Results: The administration of Wnt inhibitors significantly promoted cardiomyocyte (CM) ( P  < .0001) and vascular endothelial cell (EC) ( P  = .006) induction, which resulted in cellular components of 52.0 ± 6.1% CMs and 9.9 ± 3.0% ECs. Functional analyses revealed the significantly lowest left ventricular end-diastolic volume and highest ejection fraction in the HiCT group. Histopathologic evaluation revealed that the HiCT group had a significantly larger median engrafted area (4 weeks, GHM(-) vs HiCT: 0.4 [range, 0.2-0.7] mm 2 vs 2.2 [range, 1.8-3.1] mm 2 ; P  = .005; 12 weeks, 0 [range, 0-0.2] mm 2 vs 1.9 [range, 0.1-3.2] mm 2 ; P  = .026), accompanied by the smallest scar area and highest vascular density at the MI border zone.
Conclusions: Transplantation of HiCTs generated from clinical-grade hiPSCs exhibited a prominent therapeutic potential in a rat MI model and may provide a promising therapeutic strategy in cardiac regenerative medicine.
(© 2021 The Author(s).)
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فهرسة مساهمة: Keywords: 3D, 3-dimensional; CM, cardiomyocyte; CUBIC, clear, unobstructed brain imaging cocktails and computational analysis sample; EC, endothelial cell; ESC, embryonic stem cell; FBS, fetal bovine serum; FS, fractional shortening; GHM, gelatin hydrogel microsphere; GMP, good manufacturing protocol; HLA, human leukocyte antigen; HiCT, human induced pluripotent stem cell–derived cardiac tissue; LSFM, light sheet fluorescence microscopy; LV, left ventricular; LVDd, left ventricular end-diastolic dimension; LVDs, left ventricular end-systolic dimension; LVEDV, left ventricular end-diastolic volume; LVEF, left ventricular ejection fraction; MC, mural cell; MI, myocardial infarction; SD, standard deviation; cTnT, cardiac isoform of troponin T; cardiac regenerative therapy; heart failure; hiPSC, human induced pluripotent stem cell; iPSC, induced pluripotent stem cell; induced pluripotent stem cell; transplantation; vWF, von Willebrand factor; αMEM, alpha minimum essential medium
تواريخ الأحداث: Date Created: 20220825 Latest Revision: 20220826
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC9390608
DOI: 10.1016/j.xjon.2021.09.038
PMID: 36004071
قاعدة البيانات: MEDLINE
الوصف
تدمد:2666-2736
DOI:10.1016/j.xjon.2021.09.038