Hypoxia-preconditioned MSCs Have Superior Effect in Ameliorating Renal Function on Acute Renal Failure Animal Model


  • Agung Putra Stem Cell and Cancer Research (SCCR) Laboratory, Medical Faculty, UNISSULA, Semarang, Indonesia; Department of Postgraduate Biomedical Science, Medical Faculty, UNISSULA, Semarang, Indonesia; Departement of Pathological Anatomy of Medical Faculty, UNISSULA, Semarang, Indonesia http://orcid.org/0000-0003-4261-9437
  • Dannis Pertiwi Department of Clinical Pathology, UNISSULA, Semarang, Indonesia
  • Meidona Nurul Milla Department of Anatomy, Medical Faculty, UNISSULA, Semarang, Indonesia
  • Ulfah Dian Indrayani Department of Histology, Medical Faculty, UNISSULA, Semarang, Indonesia
  • Durotul Jannah Department of Neurology, Medical Faculty, UNISSULA, Semarang, Indonesia
  • Menik Sahariyani Department of Parasitology, UNISSULA, Semarang, Indonesia
  • Setyo Trisnadi Department of Postgraduate Biomedical Science, Medical Faculty, UNISSULA, Semarang, Indonesia
  • Joko Wahyu Wibowo Department of Postgraduate Biomedical Science, Medical Faculty, UNISSULA, Semarang, Indonesia




HP-MSCs, N-MSCs, ARF, BUN, Creatinin


BACKGROUND: Acute renal failure (ARF) is a serious disease characterised by a rapid loss of renal functions due to nephrotoxic drug or ischemic insult. The clinical treatment approach such as dialysis techniques and continuous renal enhancement have grown rapidly during past decades. However, there is yet no significant effect in improving renal function. Hypoxia-preconditioned mesenchymal stem cells (HP-MSCs) have positive effects on the in vitro survival and stemness, in addition to angiogenic potential.

AIM: In this study, we aimed to analyse the effect of HP-MSCs administration in improving renal function, characterised by blood urea nitrogen (BUN) and creatinine level.

METHODS: A group of 15 male Wistar rats weighing 250 g to 300 g were used in this study (n = 5 for each group). Rats were randomly distributed into 3 groups: Vehicle control (Veh) as a control group, HP-MSCs and normoxia MSCs (N-MSCs) as the treatment group. Renal function was evaluated based on the BUN and creatinine levels using the colourimetric method on day 5 and 13. The histological analysis using HE staining was performed on day 13.

RESULTS: The result showed there is a significant decrease in BUN and creatinine level (p < 0.05). The histological analysis of renal tissue also showed a significant decrease between Veh and treatment group (p < 0.05).

CONCLUSION: Based on this study, we conclude that HP-MSCs have a superior beneficial effect than N-MSCs in improving renal function in an animal model of gentamicin-induced ARF.


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Albright Jr RC. Acute renal failure: a practical update. Mayo Clinic Proceedings. 2001; 76(1):67-74). https://doi.org/10.4065/76.1.67 PMid:11155415 DOI: https://doi.org/10.4065/76.1.67

Ciriano ME, Porta JP, de Vera Floristán CV, García SO, Lipe RÃ, de Vera Floristán JV. Morbimortalidad del fracaso renal agudo en la Unidad de Cuidados Críticos de un hospital comarcal. Revista Espa-ola de Anestesiología y Reanimación. 2018.

Demirjian SG. Renal Replacement Therapy for Acute Renal Injury : We Need Better Therapy. 2011; 174:242–51. DOI: https://doi.org/10.1159/000329402

Ta M, Choi YO, Atouf FO, Heol C, Park H, Lumelsky NA. The Defined Combination of Growth Factors Controls Generation of Long-Term-Replicating Islet Progenitor-Like Cells from Cultures of Adult Mouse Pancreas. Stem Cells. 2006; 24:1738–49. https://doi.org/10.1634/stemcells.2005-0367 PMid:16556710 DOI: https://doi.org/10.1634/stemcells.2005-0367

Lameire N, Van Biesen W, Vanholder R. The changing epidemiology of acute renal failure. Nat Clin Pract Nephrol. 2006; 2(7):364–77. https://doi.org/10.1038/ncpneph0218 PMid:16932465 DOI: https://doi.org/10.1038/ncpneph0218

Ren M, Peng W, Yang Z, Sun X, Zhang S, Wang Z, et al. Allogeneic Adipose-Derived Stem Cells With Low Immunogenicity Constructing Tissue-Engineered Bone for Repairing Bone Defects in Pigs. 2012; 21:2711–21. DOI: https://doi.org/10.3727/096368912X654966

Dominici M, Blanc K Le, Mueller I, Marini FC, Krause DS, Deans RJ, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006; 8(4):315–7. https://doi.org/10.1080/14653240600855905 PMid:16923606 DOI: https://doi.org/10.1080/14653240600855905

Sarugaser R, Hanoun L, Keating A, Stanford WL, Davies JE. Human Mesenchymal Stem Cells Self-Renew and Differentiate According to a Deterministic Hierarchy. 2009; 4(8). DOI: https://doi.org/10.1371/journal.pone.0006498

Lee MJ, Kim J, Lee K Il, Shin JM, Chae J Il, Chung HM. Enhancement of wound healing by secretory factors of endothelial precursor cells derived from human embryonic stem cells. Cytotherapy. 2011; 13(2):165–78. https://doi.org/10.3109/14653249.2010.512632 PMid:21235296 DOI: https://doi.org/10.3109/14653249.2010.512632

Pattappa G, Thorpe SD, Jegard NC, Heywood HK, de Bruijn JD, Lee DA. Continuous and uninterrupted oxygen tension influences the colony formation and oxidative metabolism of human mesenchymal stem cells. Tissue Engineering Part C: Methods. 2012; 19(1):68-79. https://doi.org/10.1089/ten.tec.2011.0734 PMid:22731854 DOI: https://doi.org/10.1089/ten.tec.2011.0734

Liu Y, Chiang C, Hung S, Chian C. Hypoxia-preconditioned mesenchymal stem cells ameliorate ischemia/reperfusion-induced lung injury. 2017; 1–20. DOI: https://doi.org/10.1371/journal.pone.0187637

Majmundar AJ, Wong WJ, Simon MC. Hypoxia-inducible factors and the response to hypoxic stress. Molecular cell. 2010; 40(2):294-309. https://doi.org/10.1016/j.molcel.2010.09.022 PMid:20965423 PMCid:PMC3143508 DOI: https://doi.org/10.1016/j.molcel.2010.09.022

Hung SC, Pochampally RR, Hsu SC, Sanchez C, Chen SC, Spees J, Prockop DJ. Short-term exposure of multipotent stromal cells to low oxygen increases their expression of CX3CR1 and CXCR4 and their engraftment in vivo. PloS one. 2007; 2(5):e416. https://doi.org/10.1371/journal.pone.0000416 PMid:17476338 PMCid:PMC1855077 DOI: https://doi.org/10.1371/journal.pone.0000416

Nugraha A, Putra A. Tumor necrosis factor-α-activated mesenchymal stem cells accelerate wound healing through vascular endothelial growth factor regulation in rats. 2018; 37(2):125–32. DOI: https://doi.org/10.18051/UnivMed.2018.v37.135-142

Lu L, Zhao Q, Wang X, Xu Z, Lu Y, Chen Z, et al. Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials Lu-Lu. Hematol J. 2006; 91(8).

Chen Y-T, Sun C-K, Lin Y-C, Chang L-T, Chen Y-L, Tsai T-H, et al. Adipose-Derived Mesenchymal Stem Cell Protects Kidneys against Ischemia-Reperfusion Injury through Suppressing Oxidative Stress and Inflammatory Reaction. J Transl Med. 2011; 9(51). https://doi.org/10.1186/1479-5876-9-51 DOI: https://doi.org/10.1186/1479-5876-9-51

Sa AE, A HA, A SM, A FA, Soliman R. Bone Marrow Derived Mesenchymal Stem Cell Therapy in Induced Acute Renal Injury in Adult Male Albino Rats. J Cytol Histol. 2017; 8(2).

Lee RH, Seo MJ, Reger RL, Spees JL, Pulin AA, Olson SD, Prockop DJ. Multipotent stromal cells from human marrow home to and promote repair of pancreatic islets and renal glomeruli in diabetic NOD/scid mice. Proceedings of the National Academy of Sciences. 2006; 103(46):17438-43. https://doi.org/10.1073/pnas.0608249103 PMid:17088535 PMCid:PMC1634835 DOI: https://doi.org/10.1073/pnas.0608249103

Ding DC, Shyu WC, Lin SZ. Mesenchymal stem cells. Cell transplantation. 2011; 20(1):5-14. https://doi.org/10.3727/096368910X PMid:21396235 DOI: https://doi.org/10.3727/096368910X

Cybulsky A V, Mctavish AJ, Papillon J, Takano T. Role of Extracellular Matrix and Ras in Regulation of Glomerular Epithelial Cell Proliferation. 1999; 154(3):899–908. DOI: https://doi.org/10.1016/S0002-9440(10)65337-0

Haque N, Rahman MT, KAsim NHA, Alabsi AM. Hypoxic culture conditions as a solution for mesenchymal stem cell based regenerative therapy. Scientific World Journal. 2013; 2013. DOI: https://doi.org/10.1155/2013/632972

Putra A, Ridwan FB, Putridewi AI, Kustiyah AR, Wirastuti K, Sadyah NA, Rosdiana I, Munir D. 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. https://doi.org/10.3889/oamjms.2018.404 DOI: https://doi.org/10.3889/oamjms.2018.404

Matsumoto K, Nakamura T. Hepatocyte growth factor: Renotropic role and potential therapeutics for renal diseases. Kidney Int. 2001; 59(6):2023–38. https://doi.org/10.1046/j.1523-1755.2001.00717.x PMid:11380804 DOI: https://doi.org/10.1046/j.1523-1755.2001.0590062023.x

Faubel S, Lewis EC, Reznikov L, Ljubanovic D, Hoke TS, Somerset H, et al. Cisplatin-Induced Acute Renal Failure Is Associated with an Increase in the Cytokines Interleukin (IL) -1 beta, IL-18, IL-6, and Neutrophil Infiltration in the Kidney. Pharmacology. 2007; 322(1):8–15. DOI: https://doi.org/10.1124/jpet.107.119792

Selby NM, Shaw S, Woodier N, Fluck RJ, Kolhe N V. Gentamicin-associated acute kidney injury. Qjm. 2009; 102(12):873–80. https://doi.org/10.1093/qjmed/hcp143 PMid:19820138 DOI: https://doi.org/10.1093/qjmed/hcp143

Beckermann B, Kallifatidis G, Groth A, Frommhold D, Apel A, Mattern J, et al. VEGF expression by mesenchymal stem cells contributes to angiogenesis in pancreatic carcinoma. Br J Cancer. 2008; 99:622–31. https://doi.org/10.1038/sj.bjc.6604508 PMid:18665180 PMCid:PMC2527820 DOI: https://doi.org/10.1038/sj.bjc.6604508

Liang Y, Brekken RA, Hyder SM. Vascular endothelial growth factor induces proliferation of breast cancer cells and inhibits the anti-proliferative activity of anti-hormones. Endocr Relat Cancer. 2006; 13(3):905–19. https://doi.org/10.1677/erc.1.01221 PMid:16954439 DOI: https://doi.org/10.1677/erc.1.01221



How to Cite

Putra A, Pertiwi D, Milla MN, Indrayani UD, Jannah D, Sahariyani M, Trisnadi S, Wibowo JW. Hypoxia-preconditioned MSCs Have Superior Effect in Ameliorating Renal Function on Acute Renal Failure Animal Model. Open Access Maced J Med Sci [Internet]. 2019 Jan. 30 [cited 2024 Jun. 17];7(3):305-10. Available from: https://oamjms.eu/index.php/mjms/article/view/oamjms.2019.049



A - Basic Science

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