Cytotechnology

, Volume 70, Issue 1, pp 103–117 | Cite as

Lipocalin 2 enhances mesenchymal stem cell-based cell therapy in acute kidney injury rat model

  • Mehryar Habibi Roudkenar
  • Raheleh Halabian
  • Hossein Abdul Tehrani
  • Fatemeh Amiri
  • Ali Jahanian-Najafabadi
  • Amaneh Mohammadi Roushandeh
  • Zahra Abbasi-Malati
  • Yoshikazu kuwahara
Original Article

Abstract

Acute kidney injury (AKI) is one of the most common health-threatening diseases in the world. There is still no effective medical treatment for AKI. Recently, Mesenchymal stem cell (MSC)-based therapy has been proposed for treatment of AKI. However, the microenvironment of damaged kidney tissue is not favorable for survival of MSCs which would be used for therapeutic intervention. In this study, we genetically manipulated MSCs to up-regulate lipocalin-2 (Lcn2) and investigated whether the engineered MSCs (MSC-Lcn2) could improve cisplatin-induced AKI in a rat model. Our results revealed that up-regulation of Lcn2 in MSCs efficiently enhanced renal function. MSC Lcn2 up-regulates expression of HGF, IGF, FGF and VEGF growth factors. In addition, they reduced molecular biomarkers of kidney injury such as KIM-1 and Cystatin C, while increased the markers of proximal tubular epithelium such as AQP-1 and CK18 following cisplatin-induced AKI. Overall, here we over-expressed Lcn2, a well-known cytoprotective factor against acute ischemic renal injury, in MSCs. This not only potentiated beneficial roles of MSCs for cell therapy purposes but also suggested a new modality for treatment of AKI.

Keywords

Mesenchymal stem cells Lipocalin 2 Acute kidney injury Cell therapy 

Notes

Acknowledgements

This study was financially supported by the Iran National Science Foundation (INSF).

Compliance with ethical standards

Conflict of interest

The authors declare that there is no any conflict of interest.

Supplementary material

10616_2017_107_MOESM1_ESM.jpg (179 kb)
Supplementary Fig. 1 Optimization of cisplatin doses to induce acute kidney injury. Acute renal injury was induced by different intraperitoneal (IP) injection of cisplatin concentrations. Blood samples were collected 24, 48 and 72 h after cisplatin treatment, and then the levels of (a) Blood Urine Nitrogen (BUN) and (b) Serum Creatinine (SCr) were measured. Control group of rats were injected with normal saline. Results showed that 48 h after employing 13 and 16 mg/kg cisplatin, the levels of BUN and SCr increased significantly. 16 mg/kg cisplatin after 72 h was lethal for rats. Data are expressed as means ± SD. (n = 10 rat per each groups). (Mean ± SD; *p < 0.05, **p < 0.01, and ***p < 0.001). (JPEG 178 kb)
10616_2017_107_MOESM2_ESM.jpg (154 kb)
Supplementary Figure 2 Survival rate of rats 14 days after AKI. 95% of rats injected with MSC-Lcn2 were still alive on day 14, while the survival rate of rats injected with MSCs and MSC-V decreased dramatically. (Mean ± SD; *p < 0.5, **p < 0.01, and ***p < 0.001). (JPEG 153 kb)

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Copyright information

© Springer Science+Business Media Dordrecht 2017

Authors and Affiliations

  • Mehryar Habibi Roudkenar
    • 1
    • 2
  • Raheleh Halabian
    • 3
  • Hossein Abdul Tehrani
    • 3
  • Fatemeh Amiri
    • 4
  • Ali Jahanian-Najafabadi
    • 5
  • Amaneh Mohammadi Roushandeh
    • 6
  • Zahra Abbasi-Malati
    • 4
  • Yoshikazu kuwahara
    • 7
  1. 1.Department of Medical Biotechnology, Paramedicine FacultyGuilan University of Medical SciencesRashtIran
  2. 2.Neuroscience Research CenterGuilan University of Medical SciencesRashtIran
  3. 3.Department of Medical Biotechnology, Faculty of Medical SciencesTarbiat Modares UniversityTehranIran
  4. 4.Blood Transfusion Research CenterHigh Institute for Research and Education in Transfusion MedicineTehranIran
  5. 5.Department of Pharmaceutical Biotechnology, and Isfahan Pharmaceutical Sciences Research Center, School of PharmacyIsfahan University of Medical Sciences and Health ServicesIsfahanIran
  6. 6.Anatomical Sciences Department, Medicine FacultyHamadan University of Medical SciencesHamadanIran
  7. 7.Department of Radiation Biology and Medicine, Faculty of MedicineTohoku Medical and Pharmaceutical UniversitySendaiJapan

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