| 3 | A novel mesenchymal stem cell-based regimen for acute myeloid leukemia differentiation therapy显示文摘Currently the main treatment of acute myeloid leukemia(AML)is chemotherapy combining hematopoietic stem cell transplantation.However,the unbearable side effect of chemotherapy and the high risk of life-threatening infections and disease relapse following hematopoietic stem cell transplantation restrict its application in clinical practice.Thus,there is an urgent need to develop alternative therapeutic tactics with significant efficacy and attenuated adverse effects.Here,we revealed that umbilical cord-derived mesenchymal stem cells(UC-MSC)efficiently induced AML cell differentiation by shuttling the neutrophil elastase(NE)-packaged extracellular vesicles(EVs)into AML cells.Interestingly,the generation and release of NE-packaged EVs could be dramatically increased by vitamin D receptor(VDR)activation in UC-MSC.Chemical activation of VDR by using its agonist 1a,25-dihydroxyvitamin D3 efficiently enhanced the pro-differentiation capacity of UC-MSC and then alleviated malignant burden in AML mouse model.Based on these discoveries,to evade the risk of hypercalcemia,we synthetized and identified sw-22,a novel non-steroidal VDR agonist,which exerted a synergistic prodifferentiation function with UC-MSC on mitigating the progress of AML.Collectively,our findings provided a non-gene editing MSC-based therapeutic regimen to overcome the differentiation blockade in AML. | Luchen Sun Nanfei Yang Bing Chen Yuncheng Bei Zisheng Kang Can Zhang Nan Zhang Peipei Xu Wei Yang Jia Wei Jiangqiong Ke Weijian Sun Xiaokun Li Pingping Shen | 2023 | Acta Pharmaceutica Sinica B2023，13，7： | 0 |
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