Effects of Hypoxia and Lipopolysaccharide on the Migration Capacity and Paracrine Factor Expression of Human Umbilical Cord Mesenchymal Stem Cells
-
Arfianti Arfianti
,
Vitriyanna Mutiara Yuhendri
,
Fadhilla Maulany El Fajri
,
Ulfah Ulfah
,
Rahmat Azhari Kemal
,
Nicko Pisceski Kusika Saputra
Abstract
Background: Mesenchymal stem cells (MSCs) have emerged as a promising strategy for tissue regeneration. Although hypoxia or lipopolysaccharide (LPS) has been shown to affect the regenerative capacity of MSCs, their combined effects on MSCs are still unknown. We examined the effects of hypoxia and LPS on MSC migration rates and paracrine expression.
Materials and Methods: Umbilical cord-derived MSCs (UC-MSCs) were isolated and characterized. Wound scratch assays assessed migration and proliferation under hypoxic conditions, LPS supplementation, or both. The expression of paracrine factors was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR).
Results: Twenty-four hours post-scratching, the gap closure in UC-MSCs after both hypoxia exposure and LPS treatment was significantly enhanced than those in the control group (p=0.008) or those subjected to individual treatments (p=0.028 vs. hypoxia and p=0.0021 vs. LPS). Serum-supplemented media further maximized these synergistic effects. Combined hypoxia and LPS did not affect vascular endothelial growth factor (VEGF) mRNA levels. In contrast, both hypoxia exposure and LPS treatment decreased the transcript levels of hepatocyte growth factor (HGF), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β).
Conclusion: These findings indicate that the combination of hypoxia and LPS treatment affects the proliferative capacity of UC-MSCs, thus enhancing the MSC migration rate. However, hypoxia and LPS together reduce the expression of paracrine factors in UC-MSCs, potentially attenuating the immunomodulatory efficacy of UC-MSCs in tissue injury microenvironments.
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2. Darby IA, Hewitson TD. Hypoxia in tissue repair and fibrosis. Cell Tissue Res. 2016;365(3): 553-62.
3. Shu S, Wang Y, Zheng M, et al. Hypoxia and hypoxia-inducible factors in kidney injury and repair. Cells. 2019;8(3): 207.
4. Page MJ, Kell DB, Pretorius E. The role of lipopolysaccharide-induced cell signalling in chronic inflammation. Chronic Stress (Thousand Oaks). 2022;6: 24705470221076390.
5. Vuichard D, Ganter MT, Schimmer RC, et al. Hypoxia aggravates lipopolysaccharide-induced lung injury. Clin Exp Immunol. 2005;141(2):248-60.
6. Qiu Z, He Y, Ming H, et al. Lipopolysaccharide (LPS) aggravates high glucose- and hypoxia/reoxygenation-induced injury through activating ROS-dependent NLRP3 inflammasome-mediated pyroptosis in H9C2 cardiomyocytes. J Diabetes Res. 2019;2019: 8151836.
7. Li P, Gong Z, Shultz LD, et al. Mesenchymal stem cells: from regeneration to cancer. Pharmacol Ther. 2019;200: 42-54.
8. Kode JA, Mukherjee S, Joglekar MV, et al. Mesenchymal stem cells: immunobiology and role in immunomodulation and tissue regeneration. Cytotherapy. 2009;11(4): 377-91.
9. Műzes G, Sipos F. Mesenchymal stem cell-derived secretome: a potential therapeutic option for autoimmune and immune-mediated inflammatory diseases. Cells. 2022;11(15): 2300.
10. Ahmed LA, Al-Massri KF. Directions for enhancement of the therapeutic efficacy of mesenchymal stem cells in different neurodegenerative and cardiovascular diseases: current status and future perspectives. Curr Stem Cell Res Ther. 2021;16(7): 858-76.
11. Bagno L, Hatzistergos KE, Balkan W, et al. Mesenchymal stem cell-based therapy for cardiovascular disease: progress and challenges. Mol Ther. 2018;26(7): 1610-23.
12. Merimi M, El-Majzoub R, Lagneaux L, et al. The therapeutic potential of mesenchymal stromal cells for regenerative medicine: current knowledge and future understanding. Front Cell Dev Biol. 2021;9: 661532.
13. Alvites R, Branquinho M, Sousa AC, et al. Mesenchymal stem/stromal cells and their paracrine activity—immunomodulation mechanisms and how to influence the therapeutic potential. Pharmaceutics. 2022;14(2): 381.
14. Botusan IR, Sunkari VG, Savu O, et al. Stabilization of HIF-1α is critical to improve wound healing in diabetic mice. Proc Natl Acad Sci U S A. 2008;105(49): 19426-31.
15. Ke Q, Costa M. Hypoxia-inducible factor-1 (HIF-1). Mol Pharmacol. 2006;70(5): 1469-80.
16. El Fajri FM, Yuhendri VM, Elmi E, et al. Potential protection of mesenchymal stem cells against oxidative stress with hypoxic preconditioning and lipopolysaccharide exposure. Biomed Res and Ther. 2025;12(4): 7277–85.
17. Lee JH, Yoon YM, Lee SH. Hypoxic preconditioning promotes the bioactivities of mesenchymal stem cells via the HIF-1α-GRP78-Akt axis. Int J Mol Sci. 2017;18(6): 1320.
18. Yang Y, Lee EH, Yang Z. Hypoxia-conditioned mesenchymal stem cells in tissue regeneration application. Tissue Eng Part B Rev. 2022;28(5): 966-77.
19. Baxevanos N, Giamarellos-Bourboulis EJ, Pistiki A, et al. Bacterial translocation induces proinflammatory responses and is associated with early death in experimental severe injury. J Surg Res. 2013;185(2): 844-50.
20. Liu X, Yin S, Chen Y, et al. LPS-induced proinflammatory cytokine expression in human airway epithelial cells and macrophages via NF-κB, STAT3 or AP-1 activation. Mol Med Rep. 2018;17(4): 5484-91.
21. Ciesielska A, Matyjek M, Kwiatkowska K. TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling. Cell Mol Life Sci. 2021;78(4): 1233-61.
22. Eming SA, Wynn TA, Martin P. Inflammation and metabolism in tissue repair and regeneration. Science. 2017;356(6342): 1026-30.
23. Wang ZJ, Zhang FM, Wang LS, et al. Lipopolysaccharides can protect mesenchymal stem cells (MSCs) from oxidative stress-induced apoptosis and enhance proliferation of MSCs via Toll-like receptor(TLR)-4 and PI3K/Akt. Cell Biol Int. 2009;33(6): 665-74.
24. Kim SH, Das A, Chai JC, et al. Transcriptome sequencing wide functional analysis of human mesenchymal stem cells in response to TLR4 ligand. Sci Rep. 2016;6: 30311.
25. Arfianti A, Ulfah, Hutabarat LS, et al. Hipoxia modulates the secretion of growth factors of human umbilical cord-derived mesenchymal stem cells. BioMedicine (Taipei). 2023;13(3): 49-56.
26. Mori Y, Ohshimo J, Shimazu T, et al. Improved explant method to isolate umbilical cord-derived mesenchymal stem cells and their immunosuppressive properties. Tissue Eng Part C Methods. 2015;21(4): 367-72.
27. Yuhendri VM, Pratiwi N, Paulina AJ, et al. Vitamin D enhances migration but decreases gene expression of vascular endothelial growth factor and tumor necrosis factor-α in Wharton’s jelly mesenchymal stem cells. Indones J Med Lab Sci Technol. 2025;7(1): 49-59.
28. Bartels K, Grenz A, Eltzschig HK. Hypoxia and inflammation are two sides of the same coin. Proc Natl Acad Sci U S A. 2013;110(46): 18351-2.
29. Guo Y, Yu Y, Hu S, et al. The therapeutic potential of mesenchymal stem cells for cardiovascular diseases. Cell Death Dis. 2020;11(5): 349.
30. Fu X, Liu G, Halim A, et al. Mesenchymal stem cell migration and tissue repair. Cells. 2019;8(80: 784.
31. Rattigan Y, Hsu JM, Mishra PJ, et al. Interleukin 6 mediated recruitment of mesenchymal stem cells to the hypoxic tumor milieu. Exp Cell Res. 2010;316(20): 3417-24.
32. Naaldijk Y, Johnson AA, Ishak S, et al. Migrational changes of mesenchymal stem cells in response to cytokines, growth factors, hypoxia, and aging. Exp Cell Res. 2015;338(1): 97-104.
33. Yu Y, Wu RX, Gao LN, et al. Stromal cell-derived factor-1-directed bone marrow mesenchymal stem cell migration in response to inflammatory and/or hypoxic stimuli. Cell Adh Migr. 2016;10(4): 342-59.
34. Leijs MJC, Van Buul GM, Verhaar JAN, et al. Pre-treatment of human mesenchymal stem cells with inflammatory factors or hypoxia does not influence migration to osteoarthritic cartilage and synovium. Am J Sports Med. 2017;45(5): 1151-61.
35. Haoran S, Zhishan J, Yan M, et al. Hypoxic preconditioning enhances cellular viability and migratory ability: role of DANCR/miR-656-3p/HIF-1α axis in placental mesenchymal stem cells. Stem Cells. 2023;41(9): 877-91.
36. Wang Q, Li Y, Yuan H, et al. Hypoxia preconditioning of human amniotic mesenchymal stem cells enhances proliferation and migration and promotes their homing via the HGF/C-MET signaling axis to augment the repair of acute liver failure. Tissue Cell. 2024;87: 102326.
37. Ma M. Role of hypoxia in mesenchymal stem cells from dental pulp: influence, mechanism and application. Cell Biochem Biophys. 2024;82(2):535-47.
38. Lopez A, Marais E, Gallay N, et al. The in vitro migration capacity of human bone marrow-derived mesenchymal stem cells in response to chemokines and mesenchymal growth factors. Blood. 2005;106(11): 2315.
39. Fang J, Lu R, Lin Y, et al. Effects of sepsis serum on the fate of adipose tissue-derived stem cells. Front Biosci (Landmark Ed). 2023;28(4): 72.
40. Höving AL, Schmitz J, Schmidt KE, et al. Human blood serum induces p38-MAPK-and HSP27-dependent migration dynamics of adult human cardiac stem cells: single-cell analysis via a microfluidic-based cultivation platform. Biology (Basel). 2021;10(8): 708.
41. Agostini F, Vicinanza C, Lombardi E, et al. Ex vivo expansion in a clinical grade medium, containing growth factors from human platelets, enhances migration capacity of adipose stem cells. Front Immunol. 2024;15: 1404228.
42. Crisostomo PR, Wang Y, Markel TA, et al. Human mesenchymal stem cells stimulated by TNF-, LPS, or hypoxia produce growth factors by an NFB-B but not JNK-dependent mechanism. Am J Physiol Cell Physiol. 2008;294(3): 675-82.
43. Jia Y, Cao N, Zhai J, et al. HGF mediates clinical-grade human umbilical cord-derived mesenchymal stem cells improved functional recovery in a senescence-accelerated mouse model of Alzheimer’s disease. Adv Sci (Weinh). 2020;7(17):1903809.
44. Frisch RN, Curtis KM, Aenlle KK, et al. Hepatocyte growth factor and alternative splice variants - expression, regulation and implications in osteogenesis and bone health and repair. Expert Opin Ther Targets. 2016;20(9): 1087-98.
45. Mittal SK, Foulsham W, Shukla S, et al. Mesenchymal stromal cells modulate corneal alloimmunity via secretion of hepatocyte growth factor. Stem Cells Transl Med. 2019;8(10): 1030-40.
46. Fukushima T, Uchiyama S, Tanaka H, et al. Hepatocyte growth factor activator: A proteinase linking tissue injury with repair. Int J Mol Sci. 2018;19(11): 3435.
47. Hung SP, Yang MH, Tseng KF, et al. Hypoxia-induced secretion of TGF-β1 in mesenchymal stem cell promotes breast cancer cell progression. Cell Transplant. 2013;22(10): 1869-82.
48. Martire-Greco D, La Greca A, Castillo Montañez L, et al. Effects of bacterial lipopolysaccharide and Shiga toxin on induced pluripotent stem cell-derived mesenchymal stem cells. Shock. 2023;59(6): 941-47.
49. Liu F, Qiu H, Xue M, et al. MSC-secreted TGF-β regulates lipopolysaccharide-stimulated macrophage M2-like polarization via the Akt/FoxO1 pathway. Stem Cell Res Ther. 2019;10(1): 345.
50. Altun M, Zhao B, Velasco K, et al. Ubiquitin-specific protease 19 (USP19) regulates hypoxia-inducible factor 1α (HIF-1α) during hypoxia. J Biol Chem. 2012;287(3):1962-9.
51. Liao C, Liu Y, Lin Y, et al. Mesenchymal stem cell-conditioned medium protecting renal tubular epithelial cells by inhibiting hypoxia-inducible factor-1α and nuclear receptor coactivator-1. Curr Stem Cell Res Ther. 2024;19(10): 1369-81.
52. Kumar S, Vaidya M. Hypoxia inhibits mesenchymal stem cell proliferation through HIF1α-dependent regulation of P27. Mol Cell Biochem. 2016;415(1-2): 29–38.
53. Rana NK, Singh P, Koch B. CoCl2 simulated hypoxia induce cell proliferation and alter the expression pattern of hypoxia associated genes involved in angiogenesis and apoptosis. Biol Res. 2019;52(1):12.
54. Tripathi VK, Subramaniyan SA, Hwang I. Molecular and cellular response of co-cultured cells toward cobalt chloride (CoCl2)-induced hypoxia. ACS Omega. 2019;4(25): 20882-20893.
2. Darby IA, Hewitson TD. Hypoxia in tissue repair and fibrosis. Cell Tissue Res. 2016;365(3): 553-62.
3. Shu S, Wang Y, Zheng M, et al. Hypoxia and hypoxia-inducible factors in kidney injury and repair. Cells. 2019;8(3): 207.
4. Page MJ, Kell DB, Pretorius E. The role of lipopolysaccharide-induced cell signalling in chronic inflammation. Chronic Stress (Thousand Oaks). 2022;6: 24705470221076390.
5. Vuichard D, Ganter MT, Schimmer RC, et al. Hypoxia aggravates lipopolysaccharide-induced lung injury. Clin Exp Immunol. 2005;141(2):248-60.
6. Qiu Z, He Y, Ming H, et al. Lipopolysaccharide (LPS) aggravates high glucose- and hypoxia/reoxygenation-induced injury through activating ROS-dependent NLRP3 inflammasome-mediated pyroptosis in H9C2 cardiomyocytes. J Diabetes Res. 2019;2019: 8151836.
7. Li P, Gong Z, Shultz LD, et al. Mesenchymal stem cells: from regeneration to cancer. Pharmacol Ther. 2019;200: 42-54.
8. Kode JA, Mukherjee S, Joglekar MV, et al. Mesenchymal stem cells: immunobiology and role in immunomodulation and tissue regeneration. Cytotherapy. 2009;11(4): 377-91.
9. Műzes G, Sipos F. Mesenchymal stem cell-derived secretome: a potential therapeutic option for autoimmune and immune-mediated inflammatory diseases. Cells. 2022;11(15): 2300.
10. Ahmed LA, Al-Massri KF. Directions for enhancement of the therapeutic efficacy of mesenchymal stem cells in different neurodegenerative and cardiovascular diseases: current status and future perspectives. Curr Stem Cell Res Ther. 2021;16(7): 858-76.
11. Bagno L, Hatzistergos KE, Balkan W, et al. Mesenchymal stem cell-based therapy for cardiovascular disease: progress and challenges. Mol Ther. 2018;26(7): 1610-23.
12. Merimi M, El-Majzoub R, Lagneaux L, et al. The therapeutic potential of mesenchymal stromal cells for regenerative medicine: current knowledge and future understanding. Front Cell Dev Biol. 2021;9: 661532.
13. Alvites R, Branquinho M, Sousa AC, et al. Mesenchymal stem/stromal cells and their paracrine activity—immunomodulation mechanisms and how to influence the therapeutic potential. Pharmaceutics. 2022;14(2): 381.
14. Botusan IR, Sunkari VG, Savu O, et al. Stabilization of HIF-1α is critical to improve wound healing in diabetic mice. Proc Natl Acad Sci U S A. 2008;105(49): 19426-31.
15. Ke Q, Costa M. Hypoxia-inducible factor-1 (HIF-1). Mol Pharmacol. 2006;70(5): 1469-80.
16. El Fajri FM, Yuhendri VM, Elmi E, et al. Potential protection of mesenchymal stem cells against oxidative stress with hypoxic preconditioning and lipopolysaccharide exposure. Biomed Res and Ther. 2025;12(4): 7277–85.
17. Lee JH, Yoon YM, Lee SH. Hypoxic preconditioning promotes the bioactivities of mesenchymal stem cells via the HIF-1α-GRP78-Akt axis. Int J Mol Sci. 2017;18(6): 1320.
18. Yang Y, Lee EH, Yang Z. Hypoxia-conditioned mesenchymal stem cells in tissue regeneration application. Tissue Eng Part B Rev. 2022;28(5): 966-77.
19. Baxevanos N, Giamarellos-Bourboulis EJ, Pistiki A, et al. Bacterial translocation induces proinflammatory responses and is associated with early death in experimental severe injury. J Surg Res. 2013;185(2): 844-50.
20. Liu X, Yin S, Chen Y, et al. LPS-induced proinflammatory cytokine expression in human airway epithelial cells and macrophages via NF-κB, STAT3 or AP-1 activation. Mol Med Rep. 2018;17(4): 5484-91.
21. Ciesielska A, Matyjek M, Kwiatkowska K. TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling. Cell Mol Life Sci. 2021;78(4): 1233-61.
22. Eming SA, Wynn TA, Martin P. Inflammation and metabolism in tissue repair and regeneration. Science. 2017;356(6342): 1026-30.
23. Wang ZJ, Zhang FM, Wang LS, et al. Lipopolysaccharides can protect mesenchymal stem cells (MSCs) from oxidative stress-induced apoptosis and enhance proliferation of MSCs via Toll-like receptor(TLR)-4 and PI3K/Akt. Cell Biol Int. 2009;33(6): 665-74.
24. Kim SH, Das A, Chai JC, et al. Transcriptome sequencing wide functional analysis of human mesenchymal stem cells in response to TLR4 ligand. Sci Rep. 2016;6: 30311.
25. Arfianti A, Ulfah, Hutabarat LS, et al. Hipoxia modulates the secretion of growth factors of human umbilical cord-derived mesenchymal stem cells. BioMedicine (Taipei). 2023;13(3): 49-56.
26. Mori Y, Ohshimo J, Shimazu T, et al. Improved explant method to isolate umbilical cord-derived mesenchymal stem cells and their immunosuppressive properties. Tissue Eng Part C Methods. 2015;21(4): 367-72.
27. Yuhendri VM, Pratiwi N, Paulina AJ, et al. Vitamin D enhances migration but decreases gene expression of vascular endothelial growth factor and tumor necrosis factor-α in Wharton’s jelly mesenchymal stem cells. Indones J Med Lab Sci Technol. 2025;7(1): 49-59.
28. Bartels K, Grenz A, Eltzschig HK. Hypoxia and inflammation are two sides of the same coin. Proc Natl Acad Sci U S A. 2013;110(46): 18351-2.
29. Guo Y, Yu Y, Hu S, et al. The therapeutic potential of mesenchymal stem cells for cardiovascular diseases. Cell Death Dis. 2020;11(5): 349.
30. Fu X, Liu G, Halim A, et al. Mesenchymal stem cell migration and tissue repair. Cells. 2019;8(80: 784.
31. Rattigan Y, Hsu JM, Mishra PJ, et al. Interleukin 6 mediated recruitment of mesenchymal stem cells to the hypoxic tumor milieu. Exp Cell Res. 2010;316(20): 3417-24.
32. Naaldijk Y, Johnson AA, Ishak S, et al. Migrational changes of mesenchymal stem cells in response to cytokines, growth factors, hypoxia, and aging. Exp Cell Res. 2015;338(1): 97-104.
33. Yu Y, Wu RX, Gao LN, et al. Stromal cell-derived factor-1-directed bone marrow mesenchymal stem cell migration in response to inflammatory and/or hypoxic stimuli. Cell Adh Migr. 2016;10(4): 342-59.
34. Leijs MJC, Van Buul GM, Verhaar JAN, et al. Pre-treatment of human mesenchymal stem cells with inflammatory factors or hypoxia does not influence migration to osteoarthritic cartilage and synovium. Am J Sports Med. 2017;45(5): 1151-61.
35. Haoran S, Zhishan J, Yan M, et al. Hypoxic preconditioning enhances cellular viability and migratory ability: role of DANCR/miR-656-3p/HIF-1α axis in placental mesenchymal stem cells. Stem Cells. 2023;41(9): 877-91.
36. Wang Q, Li Y, Yuan H, et al. Hypoxia preconditioning of human amniotic mesenchymal stem cells enhances proliferation and migration and promotes their homing via the HGF/C-MET signaling axis to augment the repair of acute liver failure. Tissue Cell. 2024;87: 102326.
37. Ma M. Role of hypoxia in mesenchymal stem cells from dental pulp: influence, mechanism and application. Cell Biochem Biophys. 2024;82(2):535-47.
38. Lopez A, Marais E, Gallay N, et al. The in vitro migration capacity of human bone marrow-derived mesenchymal stem cells in response to chemokines and mesenchymal growth factors. Blood. 2005;106(11): 2315.
39. Fang J, Lu R, Lin Y, et al. Effects of sepsis serum on the fate of adipose tissue-derived stem cells. Front Biosci (Landmark Ed). 2023;28(4): 72.
40. Höving AL, Schmitz J, Schmidt KE, et al. Human blood serum induces p38-MAPK-and HSP27-dependent migration dynamics of adult human cardiac stem cells: single-cell analysis via a microfluidic-based cultivation platform. Biology (Basel). 2021;10(8): 708.
41. Agostini F, Vicinanza C, Lombardi E, et al. Ex vivo expansion in a clinical grade medium, containing growth factors from human platelets, enhances migration capacity of adipose stem cells. Front Immunol. 2024;15: 1404228.
42. Crisostomo PR, Wang Y, Markel TA, et al. Human mesenchymal stem cells stimulated by TNF-, LPS, or hypoxia produce growth factors by an NFB-B but not JNK-dependent mechanism. Am J Physiol Cell Physiol. 2008;294(3): 675-82.
43. Jia Y, Cao N, Zhai J, et al. HGF mediates clinical-grade human umbilical cord-derived mesenchymal stem cells improved functional recovery in a senescence-accelerated mouse model of Alzheimer’s disease. Adv Sci (Weinh). 2020;7(17):1903809.
44. Frisch RN, Curtis KM, Aenlle KK, et al. Hepatocyte growth factor and alternative splice variants - expression, regulation and implications in osteogenesis and bone health and repair. Expert Opin Ther Targets. 2016;20(9): 1087-98.
45. Mittal SK, Foulsham W, Shukla S, et al. Mesenchymal stromal cells modulate corneal alloimmunity via secretion of hepatocyte growth factor. Stem Cells Transl Med. 2019;8(10): 1030-40.
46. Fukushima T, Uchiyama S, Tanaka H, et al. Hepatocyte growth factor activator: A proteinase linking tissue injury with repair. Int J Mol Sci. 2018;19(11): 3435.
47. Hung SP, Yang MH, Tseng KF, et al. Hypoxia-induced secretion of TGF-β1 in mesenchymal stem cell promotes breast cancer cell progression. Cell Transplant. 2013;22(10): 1869-82.
48. Martire-Greco D, La Greca A, Castillo Montañez L, et al. Effects of bacterial lipopolysaccharide and Shiga toxin on induced pluripotent stem cell-derived mesenchymal stem cells. Shock. 2023;59(6): 941-47.
49. Liu F, Qiu H, Xue M, et al. MSC-secreted TGF-β regulates lipopolysaccharide-stimulated macrophage M2-like polarization via the Akt/FoxO1 pathway. Stem Cell Res Ther. 2019;10(1): 345.
50. Altun M, Zhao B, Velasco K, et al. Ubiquitin-specific protease 19 (USP19) regulates hypoxia-inducible factor 1α (HIF-1α) during hypoxia. J Biol Chem. 2012;287(3):1962-9.
51. Liao C, Liu Y, Lin Y, et al. Mesenchymal stem cell-conditioned medium protecting renal tubular epithelial cells by inhibiting hypoxia-inducible factor-1α and nuclear receptor coactivator-1. Curr Stem Cell Res Ther. 2024;19(10): 1369-81.
52. Kumar S, Vaidya M. Hypoxia inhibits mesenchymal stem cell proliferation through HIF1α-dependent regulation of P27. Mol Cell Biochem. 2016;415(1-2): 29–38.
53. Rana NK, Singh P, Koch B. CoCl2 simulated hypoxia induce cell proliferation and alter the expression pattern of hypoxia associated genes involved in angiogenesis and apoptosis. Biol Res. 2019;52(1):12.
54. Tripathi VK, Subramaniyan SA, Hwang I. Molecular and cellular response of co-cultured cells toward cobalt chloride (CoCl2)-induced hypoxia. ACS Omega. 2019;4(25): 20882-20893.
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| Issue | Vol 20 No 3 (2026) | |
| Section | Original Article(s) | |
| Keywords | ||
| Hypoxia; Lipopolysaccharide; Mesenchymal stem cells; Migration; Proliferation | ||
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How to Cite
1.
Arfianti A, Yuhendri V, Fajri F, Ulfah U, Kemal R, Saputra N. Effects of Hypoxia and Lipopolysaccharide on the Migration Capacity and Paracrine Factor Expression of Human Umbilical Cord Mesenchymal Stem Cells. Int J Hematol Oncol Stem Cell Res. 2026;20(3):237-248.
