Tags

Type your tag names separated by a space and hit enter

Endovenous administration of bone-marrow-derived multipotent mesenchymal stromal cells prevents renal failure in diabetic mice.
Biol Blood Marrow Transplant. 2009 Nov; 15(11):1354-65.BB

Abstract

Twenty-five to 40% of diabetic patients develop diabetic nephropathy, a clinical syndrome that comprises renal failure and increased risk of cardiovascular disease. It represents the major cause of chronic kidney disease and is associated with premature morbimortality of diabetic patients. Multipotent mesenchymal stromal cells (MSC) contribute to the regeneration of several organs, including acutely injured kidney. We sought to evaluate if MSC protect kidney function and structure when endovenously administered to mice with severe diabetes. A month after nonimmunologic diabetes induction by streptozotocin injection, C57BL/6 mice presented hyperglycemia, glycosuria, hypoinsulinemia, massive beta-pancreatic islet destruction, low albuminuria, but not renal histopathologic changes (DM mice). At this stage, one group of animals received the vehicle (untreated) and other group received 2 doses of 0.5 x 10(6) MSC/each (MSC-treated). Untreated DM mice gradually increased urinary albumin excretion and 4 months after diabetes onset, they reached values 15 times higher than normal animals. In contrast, MSC-treated DM mice maintained basal levels of albuminuria. Untreated DM mice had marked glomerular and tubular histopathologic changes (sclerosis, mesangial expansion, tubular dilatation, proteins cylinders, podocytes lost). However, MSC-treated mice showed only slight tubular dilatation. Observed renoprotection was not associated with an improvement in endocrine pancreas function in this animal model, because MSC-treated DM mice remained hyperglycemic and hypoinsulinemic, and maintained few remnant beta-pancreatic islets throughout the study period. To study MSC biodistribution, cells were isolated from isogenic mice that constitutively express GFP (MSC(GFP)) and endovenously administered to DM mice. Although at very low levels, donor cells were found in kidney of DM mice 3 month after transplantation. Presented preclinical results support MSC administration as a cell therapy strategy to prevent chronic renal diseases secondary to diabetes.

Authors+Show Affiliations

Instituto de Ciencias, Facultad de Medicina Clínica Alemana Universidad del Desarrollo, Santiago, Chile.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19822294

Citation

Ezquer, Fernando, et al. "Endovenous Administration of Bone-marrow-derived Multipotent Mesenchymal Stromal Cells Prevents Renal Failure in Diabetic Mice." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 15, no. 11, 2009, pp. 1354-65.
Ezquer F, Ezquer M, Simon V, et al. Endovenous administration of bone-marrow-derived multipotent mesenchymal stromal cells prevents renal failure in diabetic mice. Biol Blood Marrow Transplant. 2009;15(11):1354-65.
Ezquer, F., Ezquer, M., Simon, V., Pardo, F., Yañez, A., Carpio, D., & Conget, P. (2009). Endovenous administration of bone-marrow-derived multipotent mesenchymal stromal cells prevents renal failure in diabetic mice. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 15(11), 1354-65. https://doi.org/10.1016/j.bbmt.2009.07.022
Ezquer F, et al. Endovenous Administration of Bone-marrow-derived Multipotent Mesenchymal Stromal Cells Prevents Renal Failure in Diabetic Mice. Biol Blood Marrow Transplant. 2009;15(11):1354-65. PubMed PMID: 19822294.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endovenous administration of bone-marrow-derived multipotent mesenchymal stromal cells prevents renal failure in diabetic mice. AU - Ezquer,Fernando, AU - Ezquer,Marcelo, AU - Simon,Valeska, AU - Pardo,Fabian, AU - Yañez,Alejandro, AU - Carpio,Daniel, AU - Conget,Paulette, PY - 2009/04/01/received PY - 2009/07/24/accepted PY - 2009/10/14/entrez PY - 2009/10/14/pubmed PY - 2009/12/16/medline SP - 1354 EP - 65 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol Blood Marrow Transplant VL - 15 IS - 11 N2 - Twenty-five to 40% of diabetic patients develop diabetic nephropathy, a clinical syndrome that comprises renal failure and increased risk of cardiovascular disease. It represents the major cause of chronic kidney disease and is associated with premature morbimortality of diabetic patients. Multipotent mesenchymal stromal cells (MSC) contribute to the regeneration of several organs, including acutely injured kidney. We sought to evaluate if MSC protect kidney function and structure when endovenously administered to mice with severe diabetes. A month after nonimmunologic diabetes induction by streptozotocin injection, C57BL/6 mice presented hyperglycemia, glycosuria, hypoinsulinemia, massive beta-pancreatic islet destruction, low albuminuria, but not renal histopathologic changes (DM mice). At this stage, one group of animals received the vehicle (untreated) and other group received 2 doses of 0.5 x 10(6) MSC/each (MSC-treated). Untreated DM mice gradually increased urinary albumin excretion and 4 months after diabetes onset, they reached values 15 times higher than normal animals. In contrast, MSC-treated DM mice maintained basal levels of albuminuria. Untreated DM mice had marked glomerular and tubular histopathologic changes (sclerosis, mesangial expansion, tubular dilatation, proteins cylinders, podocytes lost). However, MSC-treated mice showed only slight tubular dilatation. Observed renoprotection was not associated with an improvement in endocrine pancreas function in this animal model, because MSC-treated DM mice remained hyperglycemic and hypoinsulinemic, and maintained few remnant beta-pancreatic islets throughout the study period. To study MSC biodistribution, cells were isolated from isogenic mice that constitutively express GFP (MSC(GFP)) and endovenously administered to DM mice. Although at very low levels, donor cells were found in kidney of DM mice 3 month after transplantation. Presented preclinical results support MSC administration as a cell therapy strategy to prevent chronic renal diseases secondary to diabetes. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/19822294/Endovenous_administration_of_bone_marrow_derived_multipotent_mesenchymal_stromal_cells_prevents_renal_failure_in_diabetic_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(09)00363-2 DB - PRIME DP - Unbound Medicine ER -