A novel mesenchymal stem cell-based regimen for acute myeloid leukemia differentiation therapy
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 r...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383523001521 |
| _version_ | 1797776659111215104 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Luchen Sun |
| collection | DOAJ |
| description | 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 1α,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 pro-differentiation 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. |
| first_indexed | 2024-03-12T22:53:05Z |
| format | Article |
| id | doaj.art-74a0d1e178e54159a8d09a795d333824 |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-03-12T22:53:05Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-74a0d1e178e54159a8d09a795d3338242023-07-20T04:38:27ZengElsevierActa Pharmaceutica Sinica B2211-38352023-07-0113730273042A novel mesenchymal stem cell-based regimen for acute myeloid leukemia differentiation therapyLuchen Sun0Nanfei Yang1Bing Chen2Yuncheng Bei3Zisheng Kang4Can Zhang5Nan Zhang6Peipei Xu7Wei Yang8Jia Wei9Jiangqiong Ke10Weijian Sun11Xiaokun Li12Pingping Shen13The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, ChinaSchool of Pharmaceutical Science, Wenzhou Medical University, Wenzhou 325035, ChinaDepartment of Hematology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210093, ChinaThe Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing 210008, ChinaState Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, ChinaCentre of Micro/Nano Manufacturing Technology (MNMT-Dublin), School of Mechanical & Materials Engineering, University College Dublin, Dublin 4, IrelandDepartment of Hematology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210093, ChinaDepartment of Surgery, Division of Cancer Biology and Therapeutics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USAThe Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing 210008, ChinaThe Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, ChinaThe Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; Corresponding authors.Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health) & School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou 325035, China; Corresponding authors.The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing 210008, China; Shenzhen Research Institute of Nanjing University, Shenzhen 518000, China; Corresponding authors.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 1α,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 pro-differentiation 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.http://www.sciencedirect.com/science/article/pii/S2211383523001521Mesenchymal stem cellAcute myeloid leukemiaExtracellular vesiclesNonsteroidal VDR modulatorsCombination therapy |
| spellingShingle | 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 A novel mesenchymal stem cell-based regimen for acute myeloid leukemia differentiation therapy Acta Pharmaceutica Sinica B Mesenchymal stem cell Acute myeloid leukemia Extracellular vesicles Nonsteroidal VDR modulators Combination therapy |
| title | A novel mesenchymal stem cell-based regimen for acute myeloid leukemia differentiation therapy |
| title_full | A novel mesenchymal stem cell-based regimen for acute myeloid leukemia differentiation therapy |
| title_fullStr | A novel mesenchymal stem cell-based regimen for acute myeloid leukemia differentiation therapy |
| title_full_unstemmed | A novel mesenchymal stem cell-based regimen for acute myeloid leukemia differentiation therapy |
| title_short | A novel mesenchymal stem cell-based regimen for acute myeloid leukemia differentiation therapy |
| title_sort | novel mesenchymal stem cell based regimen for acute myeloid leukemia differentiation therapy |
| topic | Mesenchymal stem cell Acute myeloid leukemia Extracellular vesicles Nonsteroidal VDR modulators Combination therapy |
| url | http://www.sciencedirect.com/science/article/pii/S2211383523001521 |
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