Stem Cell Research Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.
Institute of Biological Sciences, Faculty of Science, Universiti Malaya, Kuala Lumpur, Malaysia.
Cell Biochem Funct. 2023 Oct;41(7):833-844. doi: 10.1002/cbf.3833. Epub 2023 Jul 25.
Diabetes is one of the major health issues globally. Type 1 diabetes mellitus develops due to the destruction of pancreatic β cells. Mesenchymal stem cells (MSCs) having remarkable self-renewal and differentiation potential, can regenerate β cells. MSCs preconditioned with bioactive small molecules possess enhanced biological features and therapeutic potential under in vivo environment. Interestingly, compounds of naphthoquinone class possess antidiabetic and anti-inflammatory properties, and can be explored as potential candidates for preconditioning MSCs. This study analyzed the effect of lawsone-preconditioned human umbilical cord MSCs (hUMSCs) on the regeneration of β cells in the streptozotocin (STZ)-induced Type 1 diabetes (T1D) rats. hUMSCs were isolated and characterized for the presence of surface markers. MSCs were preconditioned with optimized concentration of lawsone. T1D rat model was established by injecting 50 mg/kg of STZ intraperitoneally. Untreated and lawsone-preconditioned hUMSCs were transplanted into the diabetic rats via tail vein. Fasting blood sugar and body weight were monitored regularly for 4 weeks. Pancreas was harvested and β cell regeneration was evaluated by hematoxylin and eosin staining, and gene expression analysis. Immunohistochemistry was also done to assess the insulin expression. Lawsone-preconditioned hUMSCs showed better anti-hyperglycemic effect in comparison with untreated hUMSCs. Histological analysis presented the regeneration of islets of Langerhans with upregulated expression of βcell genes and reduced expression of inflammatory markers. Immunohistochemistry revealed strong insulin expression in the preconditioned hUMSCs compared with the untreated hUMSCs. It is concluded from the present study that lawsone-preconditioned hMSCs were able to exhibit pronounced anti-hyperglycemic effect in vivo compared with hUMSCs alone.
糖尿病是全球主要的健康问题之一。1 型糖尿病的发生是由于胰腺β细胞的破坏。间充质干细胞(MSCs)具有显著的自我更新和分化潜能,可再生β细胞。经过生物活性小分子预处理的 MSCs 在体内环境下具有增强的生物学特性和治疗潜力。有趣的是,萘醌类化合物具有抗糖尿病和抗炎特性,可作为 MSC 预处理的潜在候选物进行探索。本研究分析了洛索洛芬预处理的人脐带间充质干细胞(hUMSC)对链脲佐菌素(STZ)诱导的 1 型糖尿病(T1D)大鼠β细胞再生的影响。分离并鉴定 hUMSC 表面标志物的存在。用优化浓度的 lawsone 预处理 MSC。通过腹腔注射 50mg/kg 的 STZ 建立 T1D 大鼠模型。未处理和洛索洛芬预处理的 hUMSC 通过尾静脉移植到糖尿病大鼠体内。定期监测空腹血糖和体重 4 周。采集胰腺,通过苏木精和伊红染色和基因表达分析评估β细胞再生。免疫组织化学也用于评估胰岛素表达。与未处理的 hUMSC 相比,洛索洛芬预处理的 hUMSC 显示出更好的抗高血糖作用。组织学分析显示胰岛 Langerhans 有再生,β细胞基因表达上调,炎症标志物表达减少。免疫组织化学显示预处理的 hUMSC 中胰岛素表达强于未处理的 hUMSC。本研究得出结论,与单独的 hUMSC 相比,洛索洛芬预处理的 hMSCs 能够在体内表现出明显的抗高血糖作用。