The Effect of Hypoxic Mesenchymal Cell Secretome Administration on VEGF Levels In Type 1 Diabetes Rats Model
Keywords:
MSCs, Secretome, Hypoxia, Diabetes Mellitus Type 1, VEGF
Abstract
Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterised by the cessation of insulin production due to pancreatic β-cell damage resulting in an increase in blood glucose. This study aims to analyse the effect of hypoxic secretome MSCs on the angiogenesis process through the observation of VEGF levels in T1DM rats model. The twenty animal model were randomly assigned to four groups: control T1DM, T1DM with HS-MSCs 0.5 mL intraperitoneal treatment (T1), and TIDM with hypoxic secretom mesenchymal stem cells (HS-MSCs) 1 mL intraperitoneal treatment (T2). The T1DM rats model was induced by a single intraperitoneal (IP) injection of freshly prepared streptozotocin (STZ) at a dose of 65 mg/kg of body weight. The VEGF levels was analyses under ELISA assay. The results showed that VEGF levels of T1 (68.86±4.78) and T2 (53.83±10.86) groups were significantly upregulated in treatment of HS-MSCs. Taken together, HS-MSCs potentially reduce glucose levels on T1DM through VEGF up-regulation.
References
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9. Putra A, Suwiryo ZH, Muhar AM, Widyatmoko A, Rahmi FL. The Role of Mesenchymal Stem Cells in Regulating PDGF and VEGF during Pancreatic Islet Cells Regeneration in Diabetic Animal Model. Folia Med (Plovdiv). 2021;63(6):875-883. doi:10.3897/folmed.63.e57636
10. Wise LM, Stuart GS, Real NC, Fleming SB, Mercer AA. VEGF Receptor-2 Activation Mediated by VEGF-E Limits Scar Tissue Formation Following Cutaneous Injury. Adv Wound Care (New Rochelle). 2018;7(8):283-297. doi:10.1089/wound.2016.0721
11. Daenen LGM, Roodhart JML, van Amersfoort M, et al. Chemotherapy enhances metastasis formation via VEGFR-1-expressing endothelial cells. Cancer Res. 2011;71(22):6976-6985. doi:10.1158/0008-5472.CAN-11-0627
12. Lui K. VEGF-A: The Inductive Angiogenic Factor for Development, Regeneration and Function of Pancreatic Beta Cells. Curr Stem Cell Res Ther. 2014;9(5):396-400. doi:10.2174/1574888x09666140710100603
13. Sun S, Gong F, Liu P, Miao Q. Metformin combined with quercetin synergistically repressed prostate cancer cells via inhibition of VEGF/PI3K/Akt signaling pathway. Gene. 2018;664:50-57. doi:10.1016/j.gene.2018.04.045
14. Masyithah Darlan D, Munir D, Karmila Jusuf N, Putra A, Ikhsan R, Alif I. In vitro regulation of IL-6 and TGF-ß by mesenchymal stem cells in systemic lupus erythematosus patients. Med Glas (Zenica). 2020;17(2):408-413. doi:10.17392/1186-20
15. Ikhsan R, Putra A, Munir D, Darlan DM, Suntoko B, Retno A. Mesenchymal Stem Cells Induce Regulatory T-cell Population in Human SLE. Bangladesh Journal of Medical Science. 2020;19(04):743-748.
16. Hamra NF, Putra A, Tjipta A, Amalina ND, Nasihun T. Hypoxia mesenchymal stem cells accelerate wound closure improvement by controlling α-smooth muscle actin expression in the full-thickness animal model. Open Access Maced J Med Sci. 2021;9:35-41. doi:10.3889/oamjms.2021.5537
17. Prajoko YW, Putra A, Dirja BT, Muhar AM, Amalina ND. The Ameliorating Effects of MSCs in Controlling Treg-mediated B-Cell Depletion by Indoleamine 2, 3-dioxygenase Induction in PBMC of SLE Patients. Open Access Maced J Med Sci. 2022;10:6-11. doi:10.3889/oamjms.2022.7487
18. Drawina P, Putra A, Nasihun T, Prajoko YW, Dirja BT, Amalina ND. Increased serial levels of platelet‐derived growth factor using hypoxic mesenchymal stem cell‐conditioned medium to promote closure acceler‐ ation in a full‐thickness wound. Indones J Biotechnol. 2022;27(1):36. doi:10.22146/ijbiotech.64021
19. Darlan DM, Munir D, Putra A, et al. Revealing the decrease of indoleamine 2,3-dioxygenase as a major constituent for B cells survival post-mesenchymal stem cells co-cultured with peripheral blood mononuclear cell (PBMC) of systemic lupus erythematosus (SLE) patients. Med Glas. 2022;19(1). doi:10.17392/1414-21
20. Restimulia L, Ilyas S, Munir D, et al. Rats’ umbilical-cord mesenchymal stem cells ameliorate mast cells and Hsp70 on ovalbumin-induced allergic rhinitis rats. Med Glas. 2022;19(1). doi:10.17392/1421-21
21. Putra A, Alif I, Nazar MA, et al. IL-6 and IL-8 Suppression by Bacteria-adhered Mesenchymal Stem Cells Co-cultured with PBMCs under TNF-α Exposure. In: Scitepress; 2021:311-317. doi:10.5220/0010491903110317
22. Restimulia L, Ilyas S, Munir D, et al. The CD4+CD25+FoxP3+ Regulatory T Cells Regulated by MSCs Suppress Plasma Cells in a Mouse Model of Allergic Rhinitis 256 The CD4+CD25+FoxP3+ Regulatory T Cells Regulated by MSCs Suppress Plasma Cells in a Mouse Model of Allergic Rhinitis. Published online 2021. doi:10.5455/medarh.2021.75
23. Nugraha A, Putra A. Tumor necrosis factor-α-activated mesenchymal stem cells accelerate wound healing through vascular endothelial growth factor regulation in rats. Universa Medicina. 2018;37(2):135. doi:10.18051/univmed.2018.v37.135-142
24. Yustianingsih V, Sumarawati T, Putra A. Hypoxia enhances self-renewal properties and markers of mesenchymal stem cells. Universa Medicina. 2019;38(3):164. doi:10.18051/univmed.2019.v38.164-171
25. Hartanto MM, Prajoko YW, Putra A, Amalina ND. The Combination of Mesenchymal Stem Cells and Bovine Colostrum in Reducing α-SMA Expression and NLR Levels in Wistar Rats After 50% Fibrotic Liver Resection. Open Access Maced J Med Sci. 2022;10(A):1634-1639. doi:10.3889/oamjms.2022.10557
26. Zukhiroh Z, Putra A, Chodidjah C, et al. Effect of Secretome-Hypoxia Mesenchymal Stem Cells on Regulating SOD and MMP-1 mRNA Expressions in Skin Hyperpigmentation Rats. Open Access Maced J Med Sci. 2022;10(A):1-7. doi:10.3889/oamjms.2022.10348
27. Putra, Agung; Riwanto, Ignatius; Suhartono; Putra, Taat; Wijaya I. Typhonium flagelliforme extract induce apoptosis in breast cancer stem cells by suppressing survivin. J Cancer Res Ther. 2020;16:1302-1308. doi:10.4103/jcrt.JCRT
28. Patel AN, Bartlett CE, Ichim TE. Mesenchymal Stem Cells. In: Stem Cell and Gene Therapy for Cardiovascular Disease. ; 2015. doi:10.1016/B978-0-12-801888-0.00011-4
29. van de Walle GR, de Schauwer C, Fortier LA. Mesenchymal Stem Cell Therapy. Equine Clinical Immunology. 2016;(2):297-310. doi:10.1002/9781119086512.ch31
30. Keating A. Mesenchymal stromal cells: New directions. Cell Stem Cell. 2012;10(6):709-716. doi:10.1016/j.stem.2012.05.015
31. Han Y, Li X, Zhang Y, Han Y, Chang F, Ding J. Mesenchymal Stem Cells for Regenerative Medicine. Cells. 2019;8(8):886. doi:10.3390/cells8080886
32. Gebler A, Zabel O, Seliger B. The immunomodulatory capacity of mesenchymal stem cells. Trends Mol Med. 2012;18(2):128-134. doi:10.1016/j.molmed.2011.10.004
33. Jenie RI, Amalina ND, Ilmawati GPN, et al. Cell cycle modulation of CHO-K1 cells under genistein treatment correlates with cells senescence, apoptosis and ROS level but in a dose-dependent manner. Adv Pharm Bull. 2019;9(3). doi:10.15171/apb.2019.054
34. Hermansyah D, Putra A, Munir D, Lelo A, Amalina ND, Alif I. Synergistic Effect of Curcuma longa Extract in Combination with Phyllanthus niruri Extract in Regulating Annexin A2 , Epidermal Growth Factor Receptor , Matrix Metalloproteinases , and Pyruvate Kinase M1 / 2 Signaling Pathway on Breast Cancer Stem Cell. 2021;9:271-285.
35. Tjipta A, Hermansyah D, Suzery M, Cahyono B, Amalina ND. Application of Bioinformatics Analysis to Identify Important Pathways and Hub Genes in Breast Cancer Affected by HER-2. International Journal of Cell and Biomedical Science. 2022;1(1):18-27.
36. Alkharsah KR. VEGF upregulation in viral infections and its possible therapeutic implications. Int J Mol Sci. 2018;19(6). doi:10.3390/ijms19061642
37. An Y, Liu WJ, Xue P, et al. Autophagy promotes MSC-mediated vascularization in cutaneous wound healing via regulation of VEGF secretion article. Cell Death Dis. 2018;9(2). doi:10.1038/s41419-017-0082-8
38. Gianni-Barrera R, Burger M, Wolff T, et al. Long-term safety and stability of angiogenesis induced by balanced single-vector co-expression of PDGF-BB and VEGF 164 in skeletal muscle. Sci Rep. 2016;6(January):1-15. doi:10.1038/srep21546
39. Han Y, Tao R, Han Y, et al. Microencapsulated VEGF gene-modified umbilical cord mesenchymal stromal cells promote the vascularization of tissue-engineered dermis: An experimental study. Cytotherapy. 2014;16(2):160-169. doi:10.1016/j.jcyt.2013.10.014
40. Harney AS, Arwert EN, Entenberg D, et al. Real-time imaging reveals local, transient vascular permeability, and tumor cell intravasation stimulated by TIE2hi macrophage–derived VEGFA. Cancer Discov. 2015;5(9):932-943. doi:10.1158/2159-8290.CD-15-0012
41. Samakova A, Gazova A, Sabova N, Valaskova S, Jurikova M, Kyselovic J. The pi3k/Akt pathway is associated with angiogenesis, oxidative stress and survival of mesenchymal stem cells in pathophysiologic condition in ischemia. Physiol Res. 2019;68(January 2020):S131-S138. doi:10.33549/PHYSIOLRES.934345
42. Zimna A, Kurpisz M. Hypoxia-Inducible factor-1 in physiological and pathophysiological angiogenesis: Applications and therapies. Biomed Res Int. Published online 2015. doi:10.1155/2015/549412
43. Mursiti S, Amalina ND, Marianti A. Inhibition of breast cancer cell development using Citrus maxima extract through increasing levels of Reactive Oxygen Species (ROS). J Phys Conf Ser. 2021;1918(5). doi:10.1088/1742-6596/1918/5/052005
44. Suzery M, Cahyono B, Amalina ND. Citrus sinensis (L) peels extract inhibits metastasis of breast cancer cells by targeting the downregulation matrix metalloproteinases-9. Open Access Maced J Med Sci. 2021;9(B):464-469. doi:10.3889/oamjms.2021.6072
45. Amalina ND, Wahyuni S, Harjito. Cytotoxic effects of the synthesized Citrus aurantium peels extract nanoparticles against MDA-MB-231 breast cancer cells. J Phys Conf Ser. 2021;1918(3). doi:10.1088/1742-6596/1918/3/032006
46. Suzery M, Cahyono B, Amalina ND. Citrus sinensis (L) peels extract inhibits metastasis of breast cancer cells by targeting the downregulation matrix metalloproteinases-9. Open Access Maced J Med Sci. 2021;9(B):464-469. doi:10.3889/oamjms.2021.6072
47. El-Sawah SG, Althobaiti F, Aldhahrani A, et al. Investigation of the antioxidant defensive role of both AD-MSCs and BM-MSCs in modulating the alteration in the oxidative stress status in various STZ-diabetic rats tissues. Biocell. 2021;45(6):1561-1568. doi:10.32604/BIOCELL.2021.016869
48. Putra A, Pertiwi D, Milla MN, et al. Hypoxia-preconditioned MSCs have superior effect in ameliorating renal function on acute renal failure animal model. Open Access Maced J Med Sci. 2019;7(3):305-310. doi:10.3889/oamjms.2019.049
49. Putra A, Ridwan FB, Putridewi AI, et al. The role of tnf-α induced mscs on suppressive inflammation by increasing tgf-β and il-10. Open Access Maced J Med Sci. 2018;6(10):1779-1783. doi:10.3889/oamjms.2018.404
50. Darlan DM, Munir D, Putra A, Jusuf NK. MSCs-released TGFβ1 generate CD4+CD25+Foxp3+ in T-reg cells of human SLE PBMC. Journal of the Formosan Medical Association. 2020;(xxxx):1-7. doi:10.1016/j.jfma.2020.06.028
51. Muhar AM, Putra A, Warli SM, Munir D. Hypoxia-mesenchymal stem cells inhibit intra-peritoneal adhesions formation by upregulation of the il-10 expression. Open Access Maced J Med Sci. 2019;7(23):3937-3943. doi:10.3889/oamjms.2019.713
2. Rochette L, Zeller M, Cottin Y, Vergely C. Diabetes, oxidative stress and therapeutic strategies. Biochim Biophys Acta Gen Subj. 2014;1840(9):2709-2729. doi:10.1016/j.bbagen.2014.05.017
3. WHO. Proportional mortality (% of total deaths, all ages) in Diabetes Mellitus. World Health Organization. Published online 2016:1. https://www.who.int/diabetes/country-profiles/bra_en.pdf
4. Diabetes DOF. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010;33(SUPPL. 1). doi:10.2337/dc10-S062
5. Federation ID. IDF Diabetes Atlas 6th.; 2021.
6. Speight J, Pouwer F. Diabetes mellitus, type 1. In: Cambridge Handbook of Psychology, Health and Medicine: Third Edition. Cambridge University Press; 2019:477-480. doi:10.1016/b978-3-437-42502-8.00153-4
7. Johan von Scholten B, Kreiner FF, L Gough SC, von Herrath M. Current and future therapies for type 1 diabetes. doi:10.1007/s00125-021-05398-3/Published
8. Mobasseri M, Shirmohammadi M, Amiri T, Vahed N, Fard HH, Ghojazadeh M. Prevalence and incidence of type 1 diabetes in the world: A systematic review and meta-analysis. Health Promot Perspect. 2020;10(2):98-115. doi:10.34172/hpp.2020.18
9. Putra A, Suwiryo ZH, Muhar AM, Widyatmoko A, Rahmi FL. The Role of Mesenchymal Stem Cells in Regulating PDGF and VEGF during Pancreatic Islet Cells Regeneration in Diabetic Animal Model. Folia Med (Plovdiv). 2021;63(6):875-883. doi:10.3897/folmed.63.e57636
10. Wise LM, Stuart GS, Real NC, Fleming SB, Mercer AA. VEGF Receptor-2 Activation Mediated by VEGF-E Limits Scar Tissue Formation Following Cutaneous Injury. Adv Wound Care (New Rochelle). 2018;7(8):283-297. doi:10.1089/wound.2016.0721
11. Daenen LGM, Roodhart JML, van Amersfoort M, et al. Chemotherapy enhances metastasis formation via VEGFR-1-expressing endothelial cells. Cancer Res. 2011;71(22):6976-6985. doi:10.1158/0008-5472.CAN-11-0627
12. Lui K. VEGF-A: The Inductive Angiogenic Factor for Development, Regeneration and Function of Pancreatic Beta Cells. Curr Stem Cell Res Ther. 2014;9(5):396-400. doi:10.2174/1574888x09666140710100603
13. Sun S, Gong F, Liu P, Miao Q. Metformin combined with quercetin synergistically repressed prostate cancer cells via inhibition of VEGF/PI3K/Akt signaling pathway. Gene. 2018;664:50-57. doi:10.1016/j.gene.2018.04.045
14. Masyithah Darlan D, Munir D, Karmila Jusuf N, Putra A, Ikhsan R, Alif I. In vitro regulation of IL-6 and TGF-ß by mesenchymal stem cells in systemic lupus erythematosus patients. Med Glas (Zenica). 2020;17(2):408-413. doi:10.17392/1186-20
15. Ikhsan R, Putra A, Munir D, Darlan DM, Suntoko B, Retno A. Mesenchymal Stem Cells Induce Regulatory T-cell Population in Human SLE. Bangladesh Journal of Medical Science. 2020;19(04):743-748.
16. Hamra NF, Putra A, Tjipta A, Amalina ND, Nasihun T. Hypoxia mesenchymal stem cells accelerate wound closure improvement by controlling α-smooth muscle actin expression in the full-thickness animal model. Open Access Maced J Med Sci. 2021;9:35-41. doi:10.3889/oamjms.2021.5537
17. Prajoko YW, Putra A, Dirja BT, Muhar AM, Amalina ND. The Ameliorating Effects of MSCs in Controlling Treg-mediated B-Cell Depletion by Indoleamine 2, 3-dioxygenase Induction in PBMC of SLE Patients. Open Access Maced J Med Sci. 2022;10:6-11. doi:10.3889/oamjms.2022.7487
18. Drawina P, Putra A, Nasihun T, Prajoko YW, Dirja BT, Amalina ND. Increased serial levels of platelet‐derived growth factor using hypoxic mesenchymal stem cell‐conditioned medium to promote closure acceler‐ ation in a full‐thickness wound. Indones J Biotechnol. 2022;27(1):36. doi:10.22146/ijbiotech.64021
19. Darlan DM, Munir D, Putra A, et al. Revealing the decrease of indoleamine 2,3-dioxygenase as a major constituent for B cells survival post-mesenchymal stem cells co-cultured with peripheral blood mononuclear cell (PBMC) of systemic lupus erythematosus (SLE) patients. Med Glas. 2022;19(1). doi:10.17392/1414-21
20. Restimulia L, Ilyas S, Munir D, et al. Rats’ umbilical-cord mesenchymal stem cells ameliorate mast cells and Hsp70 on ovalbumin-induced allergic rhinitis rats. Med Glas. 2022;19(1). doi:10.17392/1421-21
21. Putra A, Alif I, Nazar MA, et al. IL-6 and IL-8 Suppression by Bacteria-adhered Mesenchymal Stem Cells Co-cultured with PBMCs under TNF-α Exposure. In: Scitepress; 2021:311-317. doi:10.5220/0010491903110317
22. Restimulia L, Ilyas S, Munir D, et al. The CD4+CD25+FoxP3+ Regulatory T Cells Regulated by MSCs Suppress Plasma Cells in a Mouse Model of Allergic Rhinitis 256 The CD4+CD25+FoxP3+ Regulatory T Cells Regulated by MSCs Suppress Plasma Cells in a Mouse Model of Allergic Rhinitis. Published online 2021. doi:10.5455/medarh.2021.75
23. Nugraha A, Putra A. Tumor necrosis factor-α-activated mesenchymal stem cells accelerate wound healing through vascular endothelial growth factor regulation in rats. Universa Medicina. 2018;37(2):135. doi:10.18051/univmed.2018.v37.135-142
24. Yustianingsih V, Sumarawati T, Putra A. Hypoxia enhances self-renewal properties and markers of mesenchymal stem cells. Universa Medicina. 2019;38(3):164. doi:10.18051/univmed.2019.v38.164-171
25. Hartanto MM, Prajoko YW, Putra A, Amalina ND. The Combination of Mesenchymal Stem Cells and Bovine Colostrum in Reducing α-SMA Expression and NLR Levels in Wistar Rats After 50% Fibrotic Liver Resection. Open Access Maced J Med Sci. 2022;10(A):1634-1639. doi:10.3889/oamjms.2022.10557
26. Zukhiroh Z, Putra A, Chodidjah C, et al. Effect of Secretome-Hypoxia Mesenchymal Stem Cells on Regulating SOD and MMP-1 mRNA Expressions in Skin Hyperpigmentation Rats. Open Access Maced J Med Sci. 2022;10(A):1-7. doi:10.3889/oamjms.2022.10348
27. Putra, Agung; Riwanto, Ignatius; Suhartono; Putra, Taat; Wijaya I. Typhonium flagelliforme extract induce apoptosis in breast cancer stem cells by suppressing survivin. J Cancer Res Ther. 2020;16:1302-1308. doi:10.4103/jcrt.JCRT
28. Patel AN, Bartlett CE, Ichim TE. Mesenchymal Stem Cells. In: Stem Cell and Gene Therapy for Cardiovascular Disease. ; 2015. doi:10.1016/B978-0-12-801888-0.00011-4
29. van de Walle GR, de Schauwer C, Fortier LA. Mesenchymal Stem Cell Therapy. Equine Clinical Immunology. 2016;(2):297-310. doi:10.1002/9781119086512.ch31
30. Keating A. Mesenchymal stromal cells: New directions. Cell Stem Cell. 2012;10(6):709-716. doi:10.1016/j.stem.2012.05.015
31. Han Y, Li X, Zhang Y, Han Y, Chang F, Ding J. Mesenchymal Stem Cells for Regenerative Medicine. Cells. 2019;8(8):886. doi:10.3390/cells8080886
32. Gebler A, Zabel O, Seliger B. The immunomodulatory capacity of mesenchymal stem cells. Trends Mol Med. 2012;18(2):128-134. doi:10.1016/j.molmed.2011.10.004
33. Jenie RI, Amalina ND, Ilmawati GPN, et al. Cell cycle modulation of CHO-K1 cells under genistein treatment correlates with cells senescence, apoptosis and ROS level but in a dose-dependent manner. Adv Pharm Bull. 2019;9(3). doi:10.15171/apb.2019.054
34. Hermansyah D, Putra A, Munir D, Lelo A, Amalina ND, Alif I. Synergistic Effect of Curcuma longa Extract in Combination with Phyllanthus niruri Extract in Regulating Annexin A2 , Epidermal Growth Factor Receptor , Matrix Metalloproteinases , and Pyruvate Kinase M1 / 2 Signaling Pathway on Breast Cancer Stem Cell. 2021;9:271-285.
35. Tjipta A, Hermansyah D, Suzery M, Cahyono B, Amalina ND. Application of Bioinformatics Analysis to Identify Important Pathways and Hub Genes in Breast Cancer Affected by HER-2. International Journal of Cell and Biomedical Science. 2022;1(1):18-27.
36. Alkharsah KR. VEGF upregulation in viral infections and its possible therapeutic implications. Int J Mol Sci. 2018;19(6). doi:10.3390/ijms19061642
37. An Y, Liu WJ, Xue P, et al. Autophagy promotes MSC-mediated vascularization in cutaneous wound healing via regulation of VEGF secretion article. Cell Death Dis. 2018;9(2). doi:10.1038/s41419-017-0082-8
38. Gianni-Barrera R, Burger M, Wolff T, et al. Long-term safety and stability of angiogenesis induced by balanced single-vector co-expression of PDGF-BB and VEGF 164 in skeletal muscle. Sci Rep. 2016;6(January):1-15. doi:10.1038/srep21546
39. Han Y, Tao R, Han Y, et al. Microencapsulated VEGF gene-modified umbilical cord mesenchymal stromal cells promote the vascularization of tissue-engineered dermis: An experimental study. Cytotherapy. 2014;16(2):160-169. doi:10.1016/j.jcyt.2013.10.014
40. Harney AS, Arwert EN, Entenberg D, et al. Real-time imaging reveals local, transient vascular permeability, and tumor cell intravasation stimulated by TIE2hi macrophage–derived VEGFA. Cancer Discov. 2015;5(9):932-943. doi:10.1158/2159-8290.CD-15-0012
41. Samakova A, Gazova A, Sabova N, Valaskova S, Jurikova M, Kyselovic J. The pi3k/Akt pathway is associated with angiogenesis, oxidative stress and survival of mesenchymal stem cells in pathophysiologic condition in ischemia. Physiol Res. 2019;68(January 2020):S131-S138. doi:10.33549/PHYSIOLRES.934345
42. Zimna A, Kurpisz M. Hypoxia-Inducible factor-1 in physiological and pathophysiological angiogenesis: Applications and therapies. Biomed Res Int. Published online 2015. doi:10.1155/2015/549412
43. Mursiti S, Amalina ND, Marianti A. Inhibition of breast cancer cell development using Citrus maxima extract through increasing levels of Reactive Oxygen Species (ROS). J Phys Conf Ser. 2021;1918(5). doi:10.1088/1742-6596/1918/5/052005
44. Suzery M, Cahyono B, Amalina ND. Citrus sinensis (L) peels extract inhibits metastasis of breast cancer cells by targeting the downregulation matrix metalloproteinases-9. Open Access Maced J Med Sci. 2021;9(B):464-469. doi:10.3889/oamjms.2021.6072
45. Amalina ND, Wahyuni S, Harjito. Cytotoxic effects of the synthesized Citrus aurantium peels extract nanoparticles against MDA-MB-231 breast cancer cells. J Phys Conf Ser. 2021;1918(3). doi:10.1088/1742-6596/1918/3/032006
46. Suzery M, Cahyono B, Amalina ND. Citrus sinensis (L) peels extract inhibits metastasis of breast cancer cells by targeting the downregulation matrix metalloproteinases-9. Open Access Maced J Med Sci. 2021;9(B):464-469. doi:10.3889/oamjms.2021.6072
47. El-Sawah SG, Althobaiti F, Aldhahrani A, et al. Investigation of the antioxidant defensive role of both AD-MSCs and BM-MSCs in modulating the alteration in the oxidative stress status in various STZ-diabetic rats tissues. Biocell. 2021;45(6):1561-1568. doi:10.32604/BIOCELL.2021.016869
48. Putra A, Pertiwi D, Milla MN, et al. Hypoxia-preconditioned MSCs have superior effect in ameliorating renal function on acute renal failure animal model. Open Access Maced J Med Sci. 2019;7(3):305-310. doi:10.3889/oamjms.2019.049
49. Putra A, Ridwan FB, Putridewi AI, et al. The role of tnf-α induced mscs on suppressive inflammation by increasing tgf-β and il-10. Open Access Maced J Med Sci. 2018;6(10):1779-1783. doi:10.3889/oamjms.2018.404
50. Darlan DM, Munir D, Putra A, Jusuf NK. MSCs-released TGFβ1 generate CD4+CD25+Foxp3+ in T-reg cells of human SLE PBMC. Journal of the Formosan Medical Association. 2020;(xxxx):1-7. doi:10.1016/j.jfma.2020.06.028
51. Muhar AM, Putra A, Warli SM, Munir D. Hypoxia-mesenchymal stem cells inhibit intra-peritoneal adhesions formation by upregulation of the il-10 expression. Open Access Maced J Med Sci. 2019;7(23):3937-3943. doi:10.3889/oamjms.2019.713
Published
2023-01-31
How to Cite
Jumena, F., Amalina, N. D., & Dewi Antari, A. (2023). The Effect of Hypoxic Mesenchymal Cell Secretome Administration on VEGF Levels In Type 1 Diabetes Rats Model. International Journal of Cell and Biomedical Science, 1(3), 86-92. https://doi.org/10.59278/cbs.v1i3.22
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