Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy.
Autosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4489886?pdf=render |
| _version_ | 1818324236707561472 |
|---|---|
| author | K J Kelly Jizhong Zhang Ling Han Malgorzata Kamocka Caroline Miller Vincent H Gattone Jesus H Dominguez |
| author_facet | K J Kelly Jizhong Zhang Ling Han Malgorzata Kamocka Caroline Miller Vincent H Gattone Jesus H Dominguez |
| author_sort | K J Kelly |
| collection | DOAJ |
| description | Autosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis that intravenous renal cell transplantation with normal Sprague Dawley male kidney cells would improve the polycystic kidney disease phenotype. Cytotherapy with renal cells expressing wild type Pkhd1 and tubulogenic serum amyloid A1 had powerful and sustained beneficial effects on renal function and structure in the polycystic kidney disease model. Donor cell engraftment and both mutant and wild type Pkhd1 were found in treated but not control PCK kidneys 15 weeks after the final cell infusion. To examine the mechanisms of global protection with a small number of transplanted cells, we tested the hypothesis that exosomes derived from normal Sprague Dawley cells can limit the cystic phenotype of PCK recipient cells. We found that renal exosomes originating from normal Sprague Dawley cells carried and transferred wild type Pkhd1 mRNA to PCK cells in vivo and in vitro and restricted cyst formation by cultured PCK cells. The results indicate that transplantation with renal cells containing wild type Pkhd1 improves renal structure and function in autosomal recessive polycystic kidney disease and may provide an intra-renal supply of normal Pkhd1 mRNA. |
| first_indexed | 2024-12-13T11:25:23Z |
| format | Article |
| id | doaj.art-08db763952dd4046bdc084ca6d4dfc49 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T11:25:23Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-08db763952dd4046bdc084ca6d4dfc492022-12-21T23:48:16ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01107e013167710.1371/journal.pone.0131677Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy.K J KellyJizhong ZhangLing HanMalgorzata KamockaCaroline MillerVincent H GattoneJesus H DominguezAutosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis that intravenous renal cell transplantation with normal Sprague Dawley male kidney cells would improve the polycystic kidney disease phenotype. Cytotherapy with renal cells expressing wild type Pkhd1 and tubulogenic serum amyloid A1 had powerful and sustained beneficial effects on renal function and structure in the polycystic kidney disease model. Donor cell engraftment and both mutant and wild type Pkhd1 were found in treated but not control PCK kidneys 15 weeks after the final cell infusion. To examine the mechanisms of global protection with a small number of transplanted cells, we tested the hypothesis that exosomes derived from normal Sprague Dawley cells can limit the cystic phenotype of PCK recipient cells. We found that renal exosomes originating from normal Sprague Dawley cells carried and transferred wild type Pkhd1 mRNA to PCK cells in vivo and in vitro and restricted cyst formation by cultured PCK cells. The results indicate that transplantation with renal cells containing wild type Pkhd1 improves renal structure and function in autosomal recessive polycystic kidney disease and may provide an intra-renal supply of normal Pkhd1 mRNA.http://europepmc.org/articles/PMC4489886?pdf=render |
| spellingShingle | K J Kelly Jizhong Zhang Ling Han Malgorzata Kamocka Caroline Miller Vincent H Gattone Jesus H Dominguez Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy. PLoS ONE |
| title | Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy. |
| title_full | Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy. |
| title_fullStr | Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy. |
| title_full_unstemmed | Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy. |
| title_short | Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy. |
| title_sort | improved structure and function in autosomal recessive polycystic rat kidneys with renal tubular cell therapy |
| url | http://europepmc.org/articles/PMC4489886?pdf=render |
| work_keys_str_mv | AT kjkelly improvedstructureandfunctioninautosomalrecessivepolycysticratkidneyswithrenaltubularcelltherapy AT jizhongzhang improvedstructureandfunctioninautosomalrecessivepolycysticratkidneyswithrenaltubularcelltherapy AT linghan improvedstructureandfunctioninautosomalrecessivepolycysticratkidneyswithrenaltubularcelltherapy AT malgorzatakamocka improvedstructureandfunctioninautosomalrecessivepolycysticratkidneyswithrenaltubularcelltherapy AT carolinemiller improvedstructureandfunctioninautosomalrecessivepolycysticratkidneyswithrenaltubularcelltherapy AT vincenthgattone improvedstructureandfunctioninautosomalrecessivepolycysticratkidneyswithrenaltubularcelltherapy AT jesushdominguez improvedstructureandfunctioninautosomalrecessivepolycysticratkidneyswithrenaltubularcelltherapy |