UNASSIGNED:建立制备和移植临床级人诱导多能干细胞(hiPSC)衍生的心脏组织(HICTs)的方案,并评估动物心肌梗塞(MI)模型中的治疗潜力。
UNASSIGNED:我们同时将临床级hiPSC分化为心血管细胞谱系,无论是否给予经典Wnt抑制剂,生成5层细胞片,插入明胶水凝胶微球(GHM)(HiCTs),并将它们移植到无胸腺大鼠MI模型上。通过超声心动图和心脏磁共振成像评估心脏功能,并与假手术和无GHM的5层细胞片移植的动物进行比较。移植物存活,心室重构,并对新生血管进行组织病理学评估。
UNASSIGNED:给予Wnt抑制剂显著促进心肌细胞(CM)(P<0.0001)和血管内皮细胞(EC)(P=0.006)的诱导,产生52.0±6.1%CM和9.9±3.0%EC的细胞成分。功能分析显示,HiCT组左心室舒张末期容积最低,射血分数最高。组织病理学评估显示,HiCT组的中位移植面积明显更大(4周,GHM(-)与HiCT:0.4[范围,0.2-0.7]mm2vs2.2[范围,1.8-3.1]mm2;P=.005;12周,0[范围,0-0.2]mm2vs1.9[范围,0.1-3.2]mm2;P=.026),伴随着最小的瘢痕面积和最高的血管密度在MI边界区。
UNASSIGNED:从临床级hiPSCs产生的HCT移植在大鼠MI模型中表现出突出的治疗潜力,并可能在心脏再生医学中提供有希望的治疗策略。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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] mm2 vs 2.2 [range, 1.8-3.1] mm2; P = .005; 12 weeks, 0 [range, 0-0.2] mm2 vs 1.9 [range, 0.1-3.2] mm2; P = .026), accompanied by the smallest scar area and highest vascular density at the MI border zone.
UNASSIGNED: 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.