Authors: van Koppen, Arianne; Joles, Jaap A.; Bongartz, Lennart G.; van den Brandt, Jens; Reichardt, Holger M.; Goldschmeding, Roel; Nguyen, Tri Q.; Verhaar, Marianne C.

Source: Cell Transplantation, Volume 21, Number 10, 2012 , pp. 2299-2312(14)

Publisher: Cognizant Communication Corporation

Abstract:

Chronic kidney disease (CKD) is a major health care problem. New interventions to slow or prevent disease progression are urgently needed. We studied functional and structural effects of infusion of healthy and CKD bone marrow cells (BMCs) in a rat model of established CKD. CKD was induced by 5/6 nephrectomy (SNX) in Lewis rats, and disease progression was accelerated with L-NNA and 6% NaCl diet. Six weeks after SNX, CKD rats received healthy eGFP⁺ BMCs, CKD eGFP⁺ BMCs, or vehicle by single renal artery injection. Healthy BMCs were functionally effective 6 weeks after administration: glomerular filtration rate (GFR; inulin clearance) (0.48±0.16 vs. 0.26±0.14 ml/min/100 g) and effective renal plasma flow (RPF; PAH clearance) (1.6±0.40 vs. 1.0±0.62 ml/min/100 g) were higher in healthy BMC- versus vehicle-treated rats (both p < 0.05). Systolic blood pressure (SBP) and proteinuria were lower 5 weeks after treatment with healthy BMCs versus vehicle (SBP, 151±13 vs. 186±25 mmHg; proteinuria, 33±20 vs. 59±39 mg/day, both p < 0.05). Glomerular capillary density was increased, and less sclerosis was detected after healthy BMCs (both p < 0.05). Tubulointerstitial inflammation was also decreased after healthy BMCs. eGFP⁺ cells were present in the glomeruli and peritubular capillaries of the remnant kidney in all BMC-treated rats. CKD BMCs also reduced SBP, proteinuria, glomerulosclerosis, and tubular atrophy versus vehicle in CKD rats. However, CKD BMC therapy was not functionally effective versus vehicle [GFR: 0.28±0.09 vs. 0.26±0.16 ml/min/100 g (NS), RPF: 1.15±0.36 vs. 0.78±0.44 ml/min/100 g (NS)], and failed to decrease tubulointerstitial inflammation and fibrosis. Single intrarenal injection of healthy BMCs in rats with established CKD slowed progression of the disease, associated with increased glomerular capillary density and less sclerosis, whereas injection of CKD BMCs was less effective.

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Keywords: Bone marrow cells (BMCs); Kidney; Renal hemodynamics; Endothelium

Document Type: Research article

DOI: http://dx.doi.org/10.3727/096368912X636795

Affiliations: 1: Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands

Publication date: 2012-10-01

More about this publication?

• Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
  

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