Please enter verification code
Mesenchymal Stem Cells Home to but do not Modulate Acute Renal Injury in a Canine Model
International Journal of Biomedical Science and Engineering
Volume 2, Issue 6, December 2014, Pages: 56-66
Received: Nov. 28, 2014; Accepted: Dec. 23, 2014; Published: Dec. 29, 2014
Views 3475      Downloads 146
Gabr H., Clinical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
Abdel Aziz W. Y., Anatomy Department, Faculty of Medicine, Azhar University, Cairo, Egypt
Zahran M. E., Anatomy Department, Faculty of Medicine, Azhar University, Cairo, Egypt
Autaifi M. A., Anatomy Department, Faculty of Medicine, Azhar University, Cairo, Egypt
Aboul-Hassan G. M., Anatomy Department, Faculty of Medicine, Azhar University, Cairo, Egypt
Al-Akabawy G., Anatomy Department, Faculty of Medicine, Menofia University, Shebin elkom, Egypt
Gomaa M., Anatomy Department, Faculty of Medicine, Azhar University, Cairo, Egypt
Article Tools
Follow on us
Background: Acute kidney injury (ARI) is a common clinical event that occurs in 5-35% of all hospitalized patients and is associated with a two- to five fold increased mortality risk., with no significant improvement on pharmacologic therapy. The need for better treatment strategies for ARI called for cellular based strategies aiming to regenerate damaged tissues. Mesenchymal stem cells (MSCs) hold special promise in attenuating kidney injury, since nephrons are largely of mesenchymal origin. Objectives: The objective of this study is to evaluate the role of bone marrow derived (MSCs) in regeneration of post-ischemic acute renal injury in mongrel dogs. Material and Methods: Fifteen adult male mongrel dogs were used in this study. Animals were divided into: Group I, normal group (3 dogs); Group II, nine dogs subjected to ischemic/reperfusion injury (IRI) by clamping both renal pedicles for 60 minutes and not subjected to stem cell therapy which were further divided into: 6 dogs without sham injection, 3 sacrificed 3 days and 3 after 7 days after IRI and 3 dogs with sham injection sacrificed 7 days after IRI. and Group III (3 dogs) which underwent IRI and received systemic autologous MSC injection. This group underwent aspiration of 15-20 ml bone marrow from posterior iliac spine, mononuclear cell separation and MSC separation. MSCs were tagged by iron oxide and injected in a dose of 2million /kg systemically through the femoral vein. Evaluation of Therapeutic Effect: 1. Functional evaluation of renal functions using serum creatinine preoperative and 30 minutes, 1 day, 2days, 4days, 7days postoperative.2. Renal histology and injury scores: using H&E, PAS using morphometry. 3. Tracing of injected MSCs (homing) in renal tissues using Prussian blue staining . 4. Immunohistochemical evaluation of the apoptosis and proliferative capacity of MSCs using caspase3 and KI 67. Results: Bone marrow derived MSCs were found in the renal cortex and medulla, epithelial lining of the cortical tubules, glomeruli, the Bowman's space, in some peritubular capillaries and among the epithelial lining of the renal tubules of treated animals. However,MSCs did not undergo trans- differentiation to renal cells, There was no difference in the regeneration, apoptosis or proliferation between treated and non-treated animals. Conclusions: Injected MSCs homed to but did not affect regeneration of renal tissue after acute injury. Although MSCs did not prove to differentiate into renal tissue, they can be used as vehicles for cytokines or growth factors as they home to injured sites.
Stem Cell Therapy, Acute Renal Failure, Mesenchymal Stem Cells
To cite this article
Gabr H., Abdel Aziz W. Y., Zahran M. E., Autaifi M. A., Aboul-Hassan G. M., Al-Akabawy G., Gomaa M., Mesenchymal Stem Cells Home to but do not Modulate Acute Renal Injury in a Canine Model, International Journal of Biomedical Science and Engineering. Vol. 2, No. 6, 2014, pp. 56-66. doi: 10.11648/j.ijbse.20140206.12
Cruz DN., Bagshaw SM., Ronco C. and Ricci Z. (2010): Acute kidney injury; classification and staging. Contrib. Nephrol., 164, 24–32.
Morigi M., Imberti B., Zoja C., Corna D., Tomasoni S., Abbate M., Rottoli D., Angioletti S., Benigni A., Perico N., Alison M. and Remuzzi G. (2004): Mesenchymal stem cells are renotropic, helping to repair the kidney and improve function in acute renal failure. J. Am. Soc. Nephrol., 15:1794–1804.
Kellum JA. (2008): Acute kidney injury. Crit. Care. Med., 36(4): 141–145.
De Vries DK., Schaapherder AF. and Reinders ME. (2012): Mesenchymal stromal cells in renal ischemia/reperfusion injury. Frontiers in Immunology, 3 (162): 37-46.
Bohle A., Christensen J., Kokot F., Osswald H., Schubert B., Kendziorra H., Pressler H. and Marcovic-Lipkovski J. (1990): Acute renal failure in man: new aspects concerning pathogenesis: a morphometric study. Am. J. Nephrol., 10: 374–388.
Hiroyoshi T., Tsuchida M., Uchiyama K., Fujikawa K., Komatsu T., Kanaoka Y. and Matsuyama H. (2012): Splenectomy protects the kidneys against ischemic reperfusion injury in the rat. Transplant Immunology, 27 (1): 8–11.
Behr L., Hekmati M., Lucchini A., Houcinet K., Faussat AM., Borenstein N., Noel LH., Lelievre-Pegorier M. and Laborde K. (2009): Evaluation of the effect of autologous mesenchymal stem cell injection in a large-animal model of bilateral kidney ischaemia reperfusion injury. Cell Prolif., 42: 284 – 297.
Tögel F., Hu Z., Weiss K., Isaac J., Lange C. and Westenfelder C. (2005): Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms. Am. J. Physiol. Renal Physiol., 289 (1): F31–F42.
Herrera MB., Bussolati B., Bruno S., Morando L., Mauriello L., Romanazzi G. and Sanavio F. (2007): Exogenous mesenchymal stem cells localize to the kidney by means of CD44 following acute tubular injury. Kid. Int., 72: 430–441.
Semedo P., Wang PM., Andreucci TH., Cenedeze MA., Teixeira VP., Reis MA., Pacheco-Silva A. and Câmara NO. (2007): Mesenchymal stem cells ameliorate tissue damages triggered by renal ischemia and reperfusion injury. Transplant. Proc., 39 (2): 421–423.
Imberti B, Morigi M., Tomasoni S., Rota C., Corna D. and Longaretti L. (2007): Insulin-like growth factor-1 sustains stem cell mediated renal repair. J. Am. Soc. Nephrol., 18 (11): 2921–2928.
Lange C., Togel F., Ittrich H., Clayton F., Nolte-Ernsting C. and Zander AR. (2005): Administered mesenchymal stem cells enhance recovery from ischemia/ reperfusion induced acute renal failure in rats. Kidney Int., 68:1613–1617.
Tögel F., Weiss K., Yang Y., Hu Z., Zhang P. and Westenfelder C. (2007): Vasculotropic, paracrine actions of infused mesenchymal stem cells are important to the recovery from acute kidney injury. Am. J. Physiol. Renal Physiol. 292: F1626–F1635
Bi B., Schmitt R., Israilova M., Nishio H. and Cantley LG. (2007): Stromal cells protect against acute tubular injury via an endocrine effect. J. Am. Soc. Nephrol., 18 (9): 2486–2496.
Lin, F., Cordes K., Li L., Hood L., Couser WG., Shankland SJ. and Igarashi P. (2003): Hematopoietic stem cells contribute to the regeneration of renal tubules after renal ischemia–reperfusion injury in mice. J. Am. Soc. Nephrol., 14(5): 1188–1199.
Imasawa T., Utsunomiya Y., Kawamura T., Zhong Y. and Nagasawa R. (2001): The potential of bone marrow-derived cells to differentiate to glomerular mesangial cells. J. Am. Soc. Nephrol. 12 (7): 1401–1409.
Broekema M., Harmsen MC., Koerts JA., Petersen AH., Van Luyn MJ., Navis G. and Popa ER. (2005): Determinants of tubular bone marrow-derived cell engraftment after renal ischemia/reperfusion in rats. Kidney Int., 68: 2572–2581.
Duffield JS., Park KM., Hsiao LL., Kelley VR., Scadden DT., Ichimura T. and Bonventre JV. (2005): Restoration of tubular epithelial cells during repair of the postischemic kidney occurs independently of bone marrow-derived stem cells. J. Clin. Invest., 115: 1743–1755.
Thadhani R., Pascual M. and Bonventre JV. (1996): Acute renal failure. N. Engl. J. Med., 334:1448–1460.
Bonventre JV. (1993): Mechanisms of ischemic acute renal failure. Kidney Int. 43 (5):1160-1178.
Sutton TA. and Molitoris BA. (1998): Mechanisms of cellular injury is ischemic acute renal failure. Sem. Nephrol., 18 (5): 490–497.
Kitada H., Sugitani A., Yamamoto H., Otomo N., Okabe Y., Inoue S., Nishiyama K., Morisaki T. and Tanaka M. (2002): Attenuation of renal ischemia reperfusion injury by FR167653 in dogs. Surgery, 131(6): 654-662.
Scheiermann C., Colom B., Meda P., Patel NS., Voisin MB., Marrelli A. and Woodfin A. et al. (2009): Junctional adhesion molecule-C mediates leukocyte in filtration in response to ischemia reperfusion injury. Arterioscler. Thromb. Vasc. Biol., 29:1509–1515.
Jang HR., Ko GJ., Wasowska BA. and Rabb H. (2009): The interaction between ischemia-reperfusion and immune responses in the kidney. J Mol. Med., 87: 859–864.
Humphreys BD. and Bonventre JV. (2008): Mesenchymal stem cells in acute kidney injury. Annu. Rev. Med., 59: 311–325.
Rastegar F., Shenaq D., Huang J., Zhang W., He BC., Chen L., Zuo GW., Luo Q. and Shi Q. (2010): Mesenchymal stem cells: Molecular characteristics and clinical applications. World J. Stem Cells, 2(4): 67-80.
Science Publishing Group
1 Rockefeller Plaza,
10th and 11th Floors,
New York, NY 10020
Tel: (001)347-983-5186