Ghufran Hafiz, Azam Maryam, Mehmood Azra, Umair Muhammad, Baig Maria T, Tasneem Saba, Butt Hira, Riazuddin Sheikh
National Centre of Excellence in Molecular Biology, University of the Punjab, 87-West Canal Bank Road, Lahore, Pakistan.
Jinnah Burn and Reconstructive Surgery Centre, Allama Iqbal Medical College, Lahore, Pakistan.
J Clin Exp Hepatol. 2024 Jul-Aug;14(4):101364. doi: 10.1016/j.jceh.2024.101364. Epub 2024 Feb 12.
BACKGROUND/AIMS: Mesenchymal stem cells (MSCs) are potential alternatives for liver fibrosis treatment; however, their optimal sources remain uncertain. This study compares the ex-vivo expansion characteristics of MSCs obtained from adipose tissue (AT) and umbilical cord (UC) and assesses their therapeutic potential for liver fibrosis treatment.
Since MSCs from early to mid-passage numbers (P2-P6) are preferable for cellular therapy, we investigated the growth kinetics of AT-MSCs and UC-MSCs up to P6 and evaluated their therapeutic effects in a rat model of liver fibrosis induced by diethylnitrosamine.
Results from the expansion studies demonstrated that both cell types exhibited bona fide characteristics of MSCs, including surface antigens, pluripotent gene expression, and differentiation potential. However, AT-MSCs demonstrated a shorter doubling time (58.2 ± 7.3 vs. 82.3 ± 4.3 h; < 0.01) and a higher population doubling level (10.1 ± 0.7 vs. 8.2 ± 0.3; < 0.01) compared to UC-MSCs, resulting in more cellular yield (230 ± 9.0 vs. 175 ± 13.2 million) in less time. Animal studies demonstrated that both MSC types significantly reduced liver fibrosis ( < 0.05 vs. the control group) while also improving liver function and downregulating fibrosis-associated gene expression.
AT-MSCs and UC-MSCs effectively reduce liver fibrosis. However, adipose cultures display an advantage by yielding a higher number of MSCs in a shorter duration, rendering them a viable choice for scenarios requiring immediate single-dose administration, often encountered in clinical settings.
背景/目的：间充质干细胞（MSCs）是肝纤维化治疗的潜在替代方案；然而，其最佳来源仍不确定。本研究比较了从脂肪组织（AT）和脐带（UC）获得的MSCs的体外扩增特性，并评估了它们在肝纤维化治疗中的潜在疗效。
由于早期至中期传代次数（P2 - P6）的MSCs更适合细胞治疗，我们研究了AT - MSCs和UC - MSCs直至P6的生长动力学，并评估了它们在二乙基亚硝胺诱导的肝纤维化大鼠模型中的治疗效果。
扩增研究结果表明，两种细胞类型均表现出MSCs的真实特性，包括表面抗原、多能基因表达和分化潜能。然而，与UC - MSCs相比，AT - MSCs的倍增时间更短（58.2 ± 7.3 vs. 82.3 ± 4.3小时；P < 0.01），群体倍增水平更高（10.1 ± 0.7 vs. 8.2 ± 0.3；P < 0.01），从而在更短时间内产生更多细胞产量（230 ± 9.0 vs. 175 ± 13.2百万）。动物研究表明，两种MSCs类型均显著降低了肝纤维化（与对照组相比P < 0.05），同时还改善了肝功能并下调了纤维化相关基因表达。
AT - MSCs和UC - MSCs均能有效减轻肝纤维化。然而，脂肪组织培养物具有优势，即在更短时间内产生更多数量的MSCs，使其成为临床环境中经常遇到的需要立即单剂量给药情况的可行选择。
