Cytokines secreted from bone marrow-derived mesenchymal stem cells promote apoptosis of CD34+ leukemic stem cells as anti-cancer therapy
Objective: The effect of mesenchymal stem cells (MSCs) on the immortal characteristics of malignant cells, particularly hematologic cancer cells, remains a topic of debate, with the underlying mechanisms still requiring further elucidation. We explored the in vitro effect of the bone marrow-derived...
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Elsevier
2024-06-01
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| Series: | Regenerative Therapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352320424001445 |
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| author | Raheleh Farahzadi Ezzatollah Fathi Somayeh Vandghanooni Behnaz Valipour |
| author_facet | Raheleh Farahzadi Ezzatollah Fathi Somayeh Vandghanooni Behnaz Valipour |
| author_sort | Raheleh Farahzadi |
| collection | DOAJ |
| description | Objective: The effect of mesenchymal stem cells (MSCs) on the immortal characteristics of malignant cells, particularly hematologic cancer cells, remains a topic of debate, with the underlying mechanisms still requiring further elucidation. We explored the in vitro effect of the bone marrow-derived MSCs (BM-MSCs) on CD34+ leukemic stem cells (LSCs) enriched from the KG1-a cell line by assessing apoptosis, measuring cytokine levels, and examining TERT protein expression. Additionally, the potential signaling pathways implicated in this process, such as P53, PTEN, NF-κB, ERK1/2, Raf-1, and H-RAS, were also investigated. Methods: CD34+ LSCs were enriched from the KG1-a cell line with the magnetic activated cell sorting (MACS) method. Two cell populations (BM-MSCs and CD34+ LSCs) were co-cultured on trans well plates for seven days. Next, CD34+ LSCs were collected and subjected to Annexin V/PI assay, cytokine measurement, and western blotting. Results: BM-MSCs caused a significant increase in early and late apoptosis in the CD34+LSCs. The significant presence of interleukin (IL)-2 and IL-4 was evident in the co-cultured media. In addition, BM-MSCs significantly increased the protein expression of P53, PTEN, NF-κB, and significantly decreased p-ERK1/2, Raf-1, H-RAS, and TERT. Conclusion: The mentioned effects of IL-2 and IL-4 cytokines released from BM-MSCs on CD34+ LSCs as therapeutic agents were applied by the components of P53, PTEN, NF-κB, p-ERK1/2, Raf-1, and H-RAS signaling pathways. |
| format | Article |
| id | doaj-art-a5862029ebb84aa0a756fd0b42aa3e3e |
| institution | Kabale University |
| issn | 2352-3204 |
| language | English |
| publishDate | 2024-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Regenerative Therapy |
| spelling | doaj-art-a5862029ebb84aa0a756fd0b42aa3e3e2024-11-30T07:10:55ZengElsevierRegenerative Therapy2352-32042024-06-0126646653Cytokines secreted from bone marrow-derived mesenchymal stem cells promote apoptosis of CD34+ leukemic stem cells as anti-cancer therapyRaheleh Farahzadi0Ezzatollah Fathi1Somayeh Vandghanooni2Behnaz Valipour3Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, IranDepartment of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran; Corresponding author. Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, IranDepartment of Basic Sciences and Health, Sarab Faculty of Medical Sciences, Sarab, East Azerbaijan, Iran; Corresponding author. Department of Basic Sciences and Health, Sarab Faculty of Medical Sciences, Sarab, East Azerbaijan, Iran.Objective: The effect of mesenchymal stem cells (MSCs) on the immortal characteristics of malignant cells, particularly hematologic cancer cells, remains a topic of debate, with the underlying mechanisms still requiring further elucidation. We explored the in vitro effect of the bone marrow-derived MSCs (BM-MSCs) on CD34+ leukemic stem cells (LSCs) enriched from the KG1-a cell line by assessing apoptosis, measuring cytokine levels, and examining TERT protein expression. Additionally, the potential signaling pathways implicated in this process, such as P53, PTEN, NF-κB, ERK1/2, Raf-1, and H-RAS, were also investigated. Methods: CD34+ LSCs were enriched from the KG1-a cell line with the magnetic activated cell sorting (MACS) method. Two cell populations (BM-MSCs and CD34+ LSCs) were co-cultured on trans well plates for seven days. Next, CD34+ LSCs were collected and subjected to Annexin V/PI assay, cytokine measurement, and western blotting. Results: BM-MSCs caused a significant increase in early and late apoptosis in the CD34+LSCs. The significant presence of interleukin (IL)-2 and IL-4 was evident in the co-cultured media. In addition, BM-MSCs significantly increased the protein expression of P53, PTEN, NF-κB, and significantly decreased p-ERK1/2, Raf-1, H-RAS, and TERT. Conclusion: The mentioned effects of IL-2 and IL-4 cytokines released from BM-MSCs on CD34+ LSCs as therapeutic agents were applied by the components of P53, PTEN, NF-κB, p-ERK1/2, Raf-1, and H-RAS signaling pathways.http://www.sciencedirect.com/science/article/pii/S2352320424001445ApoptosisCD34+ leukemic stem cellsCytokinesMesenchymal stem cellsSignaling pathway |
| spellingShingle | Raheleh Farahzadi Ezzatollah Fathi Somayeh Vandghanooni Behnaz Valipour Cytokines secreted from bone marrow-derived mesenchymal stem cells promote apoptosis of CD34+ leukemic stem cells as anti-cancer therapy Regenerative Therapy Apoptosis CD34+ leukemic stem cells Cytokines Mesenchymal stem cells Signaling pathway |
| title | Cytokines secreted from bone marrow-derived mesenchymal stem cells promote apoptosis of CD34+ leukemic stem cells as anti-cancer therapy |
| title_full | Cytokines secreted from bone marrow-derived mesenchymal stem cells promote apoptosis of CD34+ leukemic stem cells as anti-cancer therapy |
| title_fullStr | Cytokines secreted from bone marrow-derived mesenchymal stem cells promote apoptosis of CD34+ leukemic stem cells as anti-cancer therapy |
| title_full_unstemmed | Cytokines secreted from bone marrow-derived mesenchymal stem cells promote apoptosis of CD34+ leukemic stem cells as anti-cancer therapy |
| title_short | Cytokines secreted from bone marrow-derived mesenchymal stem cells promote apoptosis of CD34+ leukemic stem cells as anti-cancer therapy |
| title_sort | cytokines secreted from bone marrow derived mesenchymal stem cells promote apoptosis of cd34 leukemic stem cells as anti cancer therapy |
| topic | Apoptosis CD34+ leukemic stem cells Cytokines Mesenchymal stem cells Signaling pathway |
| url | http://www.sciencedirect.com/science/article/pii/S2352320424001445 |
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