A Population of Selected Renal Cells Augments Renal Function and Extends Survival in the ZSF1 Model of Progressive Diabetic Nephropathy
New treatment paradigms that slow or reverse progression of chronic kidney disease (CKD) are needed to relieve significant patient and healthcare burdens. We have shown that a population of selected renal cells (SRCs) stabilized disease progression in a mass reduction model of CKD. Here, we further...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2013-06-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368912X653237 |
| _version_ | 1819103700013023232 |
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| author | Rusty Kelley Ph.D. Andrew Bruce Tom Spencer Eric Werdin Roger Ilagan Sumana Choudhury Elias Rivera Shay Wallace Kelly Guthrie Manuel Jayo Fengfeng Xu Anjali N. Rao Benjamin D. Humphreys Sharon Presnell Tim Bertram |
| author_facet | Rusty Kelley Ph.D. Andrew Bruce Tom Spencer Eric Werdin Roger Ilagan Sumana Choudhury Elias Rivera Shay Wallace Kelly Guthrie Manuel Jayo Fengfeng Xu Anjali N. Rao Benjamin D. Humphreys Sharon Presnell Tim Bertram |
| author_sort | Rusty Kelley Ph.D. |
| collection | DOAJ |
| description | New treatment paradigms that slow or reverse progression of chronic kidney disease (CKD) are needed to relieve significant patient and healthcare burdens. We have shown that a population of selected renal cells (SRCs) stabilized disease progression in a mass reduction model of CKD. Here, we further define the cellular composition of SRCs and apply this novel therapeutic approach to the ZSF1 rat, a model of severe progressive nephropathy secondary to diabetes, obesity, dyslipidemia, and hypertension. Injection of syngeneic SRCs into the ZSF1 renal cortex elicited a regenerative response that significantly improved survival and stabilized disease progression to renal structure and function beyond 1 year posttreatment. Functional improvements included normalization of multiple nephron structures and functions including glomerular filtration, tubular protein handling, electrolyte balance, and the ability to concentrate urine. Improvements to blood pressure, including reduced levels of circulating renin, were also observed. These functional improvements following SRC treatment were accompanied by significant reductions in glomerular sclerosis, tubular degeneration, and interstitial inflammation and fibrosis. Collectively, these data support the utility of a novel renal cell-based approach for slowing renal disease progression associated with diabetic nephropathy in the setting of metabolic syndrome, one of the most common causes of end-stage renal disease. |
| first_indexed | 2024-12-22T01:54:37Z |
| format | Article |
| id | doaj.art-7ca09f8c5c4946ad93f5e619fe9d10b5 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-22T01:54:37Z |
| publishDate | 2013-06-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-7ca09f8c5c4946ad93f5e619fe9d10b52022-12-21T18:42:50ZengSAGE PublishingCell Transplantation0963-68971555-38922013-06-012210.3727/096368912X653237A Population of Selected Renal Cells Augments Renal Function and Extends Survival in the ZSF1 Model of Progressive Diabetic NephropathyRusty Kelley Ph.D.0Andrew Bruce1Tom Spencer2Eric Werdin3Roger Ilagan4Sumana Choudhury5Elias Rivera6Shay Wallace7Kelly Guthrie8Manuel Jayo9Fengfeng Xu10Anjali N. Rao11Benjamin D. Humphreys12Sharon Presnell13Tim Bertram14Tengion, Inc., Science and Technology, Winston-Salem, NC, USATengion, Inc., Science and Technology, Winston-Salem, NC, USATengion, Inc., Science and Technology, Winston-Salem, NC, USATengion, Inc., Science and Technology, Winston-Salem, NC, USATengion, Inc., Science and Technology, Winston-Salem, NC, USATengion, Inc., Science and Technology, Winston-Salem, NC, USATengion, Inc., Science and Technology, Winston-Salem, NC, USATengion, Inc., Science and Technology, Winston-Salem, NC, USATengion, Inc., Science and Technology, Winston-Salem, NC, USATengion, Inc., Science and Technology, Winston-Salem, NC, USABrigham and Women's Hospital, Boston, MA, USABrigham and Women's Hospital, Boston, MA, USABrigham and Women's Hospital, Boston, MA, USATengion, Inc., Science and Technology, Winston-Salem, NC, USATengion, Inc., Science and Technology, Winston-Salem, NC, USANew treatment paradigms that slow or reverse progression of chronic kidney disease (CKD) are needed to relieve significant patient and healthcare burdens. We have shown that a population of selected renal cells (SRCs) stabilized disease progression in a mass reduction model of CKD. Here, we further define the cellular composition of SRCs and apply this novel therapeutic approach to the ZSF1 rat, a model of severe progressive nephropathy secondary to diabetes, obesity, dyslipidemia, and hypertension. Injection of syngeneic SRCs into the ZSF1 renal cortex elicited a regenerative response that significantly improved survival and stabilized disease progression to renal structure and function beyond 1 year posttreatment. Functional improvements included normalization of multiple nephron structures and functions including glomerular filtration, tubular protein handling, electrolyte balance, and the ability to concentrate urine. Improvements to blood pressure, including reduced levels of circulating renin, were also observed. These functional improvements following SRC treatment were accompanied by significant reductions in glomerular sclerosis, tubular degeneration, and interstitial inflammation and fibrosis. Collectively, these data support the utility of a novel renal cell-based approach for slowing renal disease progression associated with diabetic nephropathy in the setting of metabolic syndrome, one of the most common causes of end-stage renal disease.https://doi.org/10.3727/096368912X653237 |
| spellingShingle | Rusty Kelley Ph.D. Andrew Bruce Tom Spencer Eric Werdin Roger Ilagan Sumana Choudhury Elias Rivera Shay Wallace Kelly Guthrie Manuel Jayo Fengfeng Xu Anjali N. Rao Benjamin D. Humphreys Sharon Presnell Tim Bertram A Population of Selected Renal Cells Augments Renal Function and Extends Survival in the ZSF1 Model of Progressive Diabetic Nephropathy Cell Transplantation |
| title | A Population of Selected Renal Cells Augments Renal Function and Extends Survival in the ZSF1 Model of Progressive Diabetic Nephropathy |
| title_full | A Population of Selected Renal Cells Augments Renal Function and Extends Survival in the ZSF1 Model of Progressive Diabetic Nephropathy |
| title_fullStr | A Population of Selected Renal Cells Augments Renal Function and Extends Survival in the ZSF1 Model of Progressive Diabetic Nephropathy |
| title_full_unstemmed | A Population of Selected Renal Cells Augments Renal Function and Extends Survival in the ZSF1 Model of Progressive Diabetic Nephropathy |
| title_short | A Population of Selected Renal Cells Augments Renal Function and Extends Survival in the ZSF1 Model of Progressive Diabetic Nephropathy |
| title_sort | population of selected renal cells augments renal function and extends survival in the zsf1 model of progressive diabetic nephropathy |
| url | https://doi.org/10.3727/096368912X653237 |
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