Potential Therapeutic Effects of Long-Term Stem Cell Administration: Impact on the Gene Profile and Kidney Function of PKD/Mhm (Cy/ plus ) Rats

被引:2
作者
Nardozi, Daniela [1 ,2 ]
Palumbo, Stefania [1 ]
Khan, Arif ul Maula [1 ]
Sticht, Carsten [1 ]
Bieback, Karen [3 ]
Sadeghi, Samar [4 ]
Kluth, Mark Andreas [4 ]
Keese, Michael
Gretz, Norbert [1 ]
机构
[1] Heidelberg Univ, Med Fac Mannheim, Med Res Ctr, D-68167 Mannheim, Germany
[2] Univ Hosp Mannheim, Vasc Surg, D-68167 Mannheim, Germany
[3] Heidelberg Univ, Med Fac Mannheim, German Red Cross Blood Serv Baden Wurttemberg Hes, Mannheim Inst Innate Immunosci,Inst Transfus Med, D-68167 Mannheim, Germany
[4] RHEACELL GmbH & Co KG, TICEBA GmbH, D-69120 Heidelberg, Germany
关键词
cystic kidney disease (CKD); adipose-derived stromal cell (ASC); ABCB5; conditioned media; gene expression profile; GLOMERULAR-FILTRATION-RATE; UMBILICAL-CORD BLOOD; NF-KAPPA-B; POLYCYSTIC KIDNEY; BONE-MARROW; ADIPOSE-TISSUE; INJURY-REPAIR; DISEASE; PATHWAYS; MODEL;
D O I
10.3390/jcm11092601
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Cystic kidney disease (CKD) is a heterogeneous group of genetic disorders and one of the most common causes of end-stage renal disease. Here, we investigate the potential effects of long-term human stem cell treatment on kidney function and the gene expression profile of PKD/Mhm (Cy/+) rats. Human adipose-derived stromal cells (ASC) and human skin-derived ABCB5(+) stromal cells (2 x 10(6)) were infused intravenously or intraperitoneally monthly, over 6 months. Additionally, ASC and ABCB5(+)-derived conditioned media were administrated intraperitoneally. The gene expression profile results showed a significant reprogramming of metabolism-related pathways along with downregulation of the cAMP, NF-kB and apoptosis pathways. During the experimental period, we measured the principal renal parameters as well as renal function using an innovative non-invasive transcutaneous device. All together, these analyses show a moderate amelioration of renal function in the ABCB5(+) and ASC-treated groups. Additionally, ABCB5(+) and ASC-derived conditioned media treatments lead to milder but still promising improvements. Even though further analyses have to be performed, the preliminary results obtained in this study can lay the foundations for a novel therapeutic approach with the application of cell-based therapy in CKD.
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页数:16
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共 81 条
[1]   Magnetic resonance imaging evaluation of hepatic cysts in early autosomal-dominant polycystic kidney disease: The consortium for radiologic imaging studies of polycystic kidney disease cohort [J].
Bae, Kyongtae T. ;
Zhu, Fang ;
Chapman, Arlene B. ;
Torres, Vicente E. ;
Grantham, Jared J. ;
Guay-Woodford, Lisa M. ;
Baumgarten, Deborah A. ;
King, Bernard F., Jr. ;
Wetzel, Louis H. ;
Kenney, Philip J. ;
Brummer, Marijn E. ;
Bennett, William M. ;
Klahr, Saulo ;
Meyers, Catherine M. ;
Zhang, Xiaoling ;
Thompson, Paul A. ;
Miller, J. Philip .
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2006, 1 (01) :64-69
[2]   Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium - Feasibility, cell migration, and body distribution [J].
Barbash, IM ;
Chouraqui, P ;
Baron, J ;
Feinberg, MS ;
Etzion, S ;
Tessone, A ;
Miller, L ;
Guetta, E ;
Zipori, D ;
Kedes, LH ;
Kloner, RA ;
Leor, J .
CIRCULATION, 2003, 108 (07) :863-868
[3]   Polycystic kidney disease [J].
Bergmann, Carsten ;
Guay-Woodford, Lisa M. ;
Harris, Peter C. ;
Horie, Shigeo ;
Peters, Dorien J. M. ;
Torres, Vicente E. .
NATURE REVIEWS DISEASE PRIMERS, 2018, 4
[4]   Cardiovascular polycystins:: Insights from autosomal dominant polycystic kidney disease and transgenic animal models [J].
Bichet, Delphine ;
Peters, Dorien ;
Patel, Amanda Jane ;
Delmas, Patrick ;
Honore, Eric .
TRENDS IN CARDIOVASCULAR MEDICINE, 2006, 16 (08) :292-298
[5]   Location of the first genetic locus, PKDr1, controlling autosomal dominant polycystic kidney disease in Han:SPRD cy/+ rat [J].
Bihoreau, MT ;
Ceccherini, I ;
Browne, J ;
Kranzlin, B ;
Romeo, G ;
Lathrop, GM ;
James, MR ;
Gretz, N .
HUMAN MOLECULAR GENETICS, 1997, 6 (04) :609-613
[6]   Missense mutation in sterile α motif of novel protein SamCystin is associated with polycystic kidney disease in (cy/+) rat [J].
Brown, JH ;
Bihoreau, MT ;
Hoffmann, S ;
Kränzlin, B ;
Tychinskaya, I ;
Obermüller, N ;
Podlich, D ;
Boehn, SN ;
Kaisaki, PJ ;
Megel, N ;
Danoy, P ;
Copley, RR ;
Broxholme, J ;
Witzgall, R ;
Lathrop, M ;
Gretz, N ;
Gauguier, D .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2005, 16 (12) :3517-3526
[7]   Hypoxia-Inducible Factor-1α Causes Renal Cyst Expansion through Calcium-Activated Chloride Secretion [J].
Buchholz, Bjoern ;
Schley, Gunnar ;
Faria, Diana ;
Kroening, Sven ;
Willam, Carsten ;
Schreiber, Rainer ;
Klanke, Bernd ;
Burzlaff, Nicolai ;
Jantsch, Jonathan ;
Kunzelmann, Karl ;
Eckardt, Kai-Uwe .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2014, 25 (03) :465-474
[8]   Mitochondrial dysfunction in the pathophysiology of renal diseases [J].
Che, Ruochen ;
Yuan, Yanggang ;
Huang, Songming ;
Zhang, Aihua .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2014, 306 (04) :F367-F378
[9]   The societal economic burden of autosomal dominant polycystic kidney disease in the United States [J].
Cloutier, Martin ;
Manceur, Ameur M. ;
Guerin, Annie ;
Aigbogun, Myrlene Sanon ;
Oberdhan, Dorothee ;
Gauthier-Loiselle, Marjolaine .
BMC HEALTH SERVICES RESEARCH, 2020, 20 (01)
[10]   Polycystic kidney size and outcomes on peritoneal dialysis: comparison with haemodialysis [J].
Courivaud, C. ;
Roubiou, C. ;
Delabrousse, E. ;
Bresson-Vautrin, C. ;
Chalopin, J. M. ;
Ducloux, D. .
CLINICAL KIDNEY JOURNAL, 2014, 7 (02) :138-143