Fresh and cryopreserved, uncultured adipose tissue-derived stem and regenerative cells ameliorate ischemia-reperfusion-induced acute kidney injury

Nephrol Dial Transplant. 2010 Dec;25(12):3874-84. doi: 10.1093/ndt/gfq603. Epub 2010 Oct 4.

Abstract

Background: Acute kidney injury (AKI) represents a major clinical problem with high mortality and limited causal treatments. The use of cell therapy has been suggested as a potential modality to improve the course and outcome of AKI.

Methods: We investigated the possible renoprotection of freshly isolated, uncultured adipose tissue-derived stem and regenerative cells (ADRCs) before and after cryopreservation in a rat ischemia-reperfusion (I-R) model of AKI.

Results: We demonstrated that ADRC therapy drastically reduced mortality (survival 100% vs. 57%, ADRC vs. controls, respectively) and significantly reduced serum creatinine (sCr on Day 3: 3.03 ± 1.58 vs. 7.37 ± 2.32 mg/dL, ADRC vs. controls, respectively). Histological analysis further validated a significantly reduced intratubular cast formation, ameliorated acute tubular epithelial cell necrosis and mitigated macrophage infiltration. Furthermore, a reduced RNA expression of CXCL2 and IL-6 was found in the ADRC group which could explain the reduced macrophage recruitment. Use of cryopreserved ADRCs resulted in an equally high survival (90% vs. 33% in the control group) and similarly improved renal function (sCr on Day 3: 4.64 ± 2.43 vs. 7.24 ± 1.40 mg/dL in controls).

Conclusions: Collectively, these results suggest a potential clinical role for ADRC therapy in patients with AKI. Importantly, cryopreservation of ADRCs could offer an autologous treatment strategy for patients who are at high risk for AKI during planned interventions.

MeSH terms

  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / physiopathology
  • Acute Kidney Injury / prevention & control*
  • Adipose Tissue / cytology*
  • Animals
  • Cell Movement / physiology
  • Cell Proliferation
  • Cell- and Tissue-Based Therapy / methods*
  • Chemokine CXCL2 / metabolism
  • Cryopreservation*
  • Interleukin-6 / metabolism
  • Kidney Tubules / metabolism
  • Kidney Tubules / pathology
  • Kidney Tubules / physiopathology
  • Macrophages / pathology
  • Mesenchymal Stem Cell Transplantation*
  • Models, Animal
  • Necrosis
  • Rats
  • Reperfusion Injury / complications*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / physiopathology
  • Stem Cells / cytology*
  • Stem Cells / physiology

Substances

  • Chemokine CXCL2
  • Cxcl2 protein, rat
  • Interleukin-6