Institute of Molecular Cardiology, University of Louisville School of Medicine, Louisville, KY, USA.
Center for Cardiometabolic Science, University of Louisville School of Medicine, 580 South Preston St. - Rm 204B, Louisville, KY, 40202, USA.
Stem Cell Rev Rep. 2023 Oct;19(7):2429-2446. doi: 10.1007/s12015-023-10590-6. Epub 2023 Jul 28.
Although cell therapy provides benefits for outcomes of heart failure, the most optimal cell type to be used clinically remains unknown. Most of the cell products used for therapy in humans require in vitro expansion to obtain a suitable number of cells for treatment; however, the clinical background of the donor and limited starting material may result in the impaired proliferative and reparative capacity of the cells expanded in vitro. Wharton's jelly mesenchymal cells (WJ MSCs) provide a multitude of advantages over adult tissue-derived cell products for therapy. These include large starting tissue material, superior proliferative capacity, and disease-free donors. Thus, WJ MSC if effective would be the most optimal cell source for clinical use.
This study evaluated the therapeutic efficacy of Wharton's jelly (WJ) and bone marrow (BM) mesenchymal stromal cells (MSCs) in chronic ischemic cardiomyopathy in rats.
Human WJ MSCs and BM MSCs were expanded in vitro, characterized, and evaluated for therapeutic efficacy in a immunodeficient rat model of ischemic cardiomyopathy. Cardiac function was evaluated with hemodynamics and echocardiography. The extent of cardiac fibrosis, hypertrophy, and inflammation was assessed with histological analysis.
In vitro analysis revealed that WJ MSCs and BM MSCs are morphologically and immunophenotypically indistinguishable. Nevertheless, the functional analysis showed that WJ MSCs have a superior proliferative capacity, less senescent phenotype, and distinct transcriptomic profile compared to BM MSC. WJ MSCs and BM MSC injected in rat hearts chronically after MI produced a small, but not significant improvement in heart structure and function. Histological analysis showed no difference in the scar size, collagen content, cardiomyocyte cross-sectional area, and immune cell count.
Human WJ and BM MSC have a small but not significant effect on cardiac structure and function when injected intramyocardially in immunodeficient rats chronically after MI.
尽管细胞疗法为心力衰竭的预后带来了益处，但最适合临床应用的细胞类型仍不清楚。大多数用于人类治疗的细胞产品需要体外扩增，以获得足够数量的细胞进行治疗；然而，供体的临床背景和有限的起始材料可能导致体外扩增的细胞增殖和修复能力受损。Wharton 胶间充质细胞（WJ MSC）在用于治疗的成体组织来源细胞产品方面具有许多优势。这些优势包括起始组织材料丰富、增殖能力强、供体无疾病。因此，如果 WJ MSC 有效，它将是临床应用的最佳细胞来源。
本研究评估了 Wharton 胶（WJ）和骨髓（BM）间充质基质细胞（MSC）在大鼠慢性缺血性心肌病中的治疗效果。
体外扩增人 WJ MSC 和 BM MSC，对其进行鉴定，并在免疫缺陷大鼠缺血性心肌病模型中评估其治疗效果。用血流动力学和超声心动图评估心功能。用组织学分析评估心肌纤维化、肥大和炎症的程度。
体外分析显示，WJ MSC 和 BM MSC 在形态和免疫表型上无法区分。然而，功能分析表明，与 BM MSC 相比，WJ MSC 具有更强的增殖能力、更年轻的表型和独特的转录组特征。在 MI 后慢性期注射到大鼠心脏中的 WJ MSC 和 BM MSC 仅使心脏结构和功能略有改善，但无统计学意义。组织学分析显示，疤痕大小、胶原含量、心肌细胞横截面积和免疫细胞计数无差异。
在 MI 后慢性期免疫缺陷大鼠心肌内注射人 WJ 和 BM MSC 对心脏结构和功能仅有微小但无统计学意义的影响。
