Abstract
New therapeutic strategies for chronic kidney disease (CKD) are necessary to offset the rising incidence of CKD and donor shortage. Erythropoietin (EPO), a cytokine produced by fibroblast-like cells in the kidney, has recently emerged as a renoprotective factor with anti-inflammatory, antioxidant properties. This study (a) determined whether human renal cultures (human primary kidney cells [hPKC]) can be enriched in EPO-positive cells (hPKC(F+)) by using magnetic-bead sorting; (b) characterized hPKC(F+) following cell separation; and (c) established that intrarenal delivery of enriched hPKC(F+) cells would be more beneficial in treatment of renal injury, inflammation, and oxidative stress than unsorted hPKC cultures in a chronic kidney injury model. Fluorescence-activated cell sorting analysis revealed higher expression of EPO (36%) and CD73 (27%) in hPKC(F+) as compared with hPKC. After induction of renal injury, intrarenal delivery of hPKC(F+) or hPKC significantly reduced serum creatinine, interstitial fibrosis in the medulla, and abundance of CD68-positive cells in the cortex and medulla (p <. 05). However, only hPKC(F+) attenuated interstitial fibrosis in the renal cortex and decreased urinary albumin (3.5-fold) and urinary tubular injury marker kidney injury molecule 1 (16-fold). hPKC(F+) also significantly reduced levels of renal cortical monocyte chemotactic protein 1 (1.8-fold) and oxidative DNA marker 8-hydroxy-deoxyguanosine (8-OHdG) (2.4-fold). After 12 weeks, we detected few injected cells, which were localized mostly to the cortical interstitium. Although cell therapy with either hPKC(F+) or hPKC improved renal function, the hPKC(F+) subpopulation provides greater renoprotection, perhaps through attenuation of inflammation and oxidative stress. We conclude that hPKC(F+) may be used as components of cell-based therapies for degenerative kidney diseases.
| Original language | English |
|---|---|
| Pages (from-to) | 373-383 |
| Number of pages | 11 |
| Journal | Stem cells translational medicine |
| Volume | 1 |
| Issue number | 5 |
| DOIs | |
| State | Published - Dec 1 2012 |
| Externally published | Yes |
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Keywords
- Adult stem cells
- Autologous stem cell transplantation
- Cell biology
- Cellular therapy
- Erythropoietin
- Renal fibrosis
- Tissue-specific stem cells
ASJC Scopus subject areas
- Cell Biology
- Developmental Biology
- Medicine(all)
Cite this
Cell therapy with human renal cell cultures containing erythropoietin-positive cells improves chronic kidney injury. / Yamaleyeva, Liliya M.; Guimaraes-Souza, Nadia K.; Krane, Louis S.; Agcaoili, Sigrid; Gyabaah, Kenneth; Atala, Anthony; Aboushwareb, Tamer; Yoo, James J.
In: Stem cells translational medicine, Vol. 1, No. 5, 01.12.2012, p. 373-383.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cell therapy with human renal cell cultures containing erythropoietin-positive cells improves chronic kidney injury
AU - Yamaleyeva, Liliya M.
AU - Guimaraes-Souza, Nadia K.
AU - Krane, Louis S.
AU - Agcaoili, Sigrid
AU - Gyabaah, Kenneth
AU - Atala, Anthony
AU - Aboushwareb, Tamer
AU - Yoo, James J.
PY - 2012/12/1
Y1 - 2012/12/1
N2 - New therapeutic strategies for chronic kidney disease (CKD) are necessary to offset the rising incidence of CKD and donor shortage. Erythropoietin (EPO), a cytokine produced by fibroblast-like cells in the kidney, has recently emerged as a renoprotective factor with anti-inflammatory, antioxidant properties. This study (a) determined whether human renal cultures (human primary kidney cells [hPKC]) can be enriched in EPO-positive cells (hPKC(F+)) by using magnetic-bead sorting; (b) characterized hPKC(F+) following cell separation; and (c) established that intrarenal delivery of enriched hPKC(F+) cells would be more beneficial in treatment of renal injury, inflammation, and oxidative stress than unsorted hPKC cultures in a chronic kidney injury model. Fluorescence-activated cell sorting analysis revealed higher expression of EPO (36%) and CD73 (27%) in hPKC(F+) as compared with hPKC. After induction of renal injury, intrarenal delivery of hPKC(F+) or hPKC significantly reduced serum creatinine, interstitial fibrosis in the medulla, and abundance of CD68-positive cells in the cortex and medulla (p <. 05). However, only hPKC(F+) attenuated interstitial fibrosis in the renal cortex and decreased urinary albumin (3.5-fold) and urinary tubular injury marker kidney injury molecule 1 (16-fold). hPKC(F+) also significantly reduced levels of renal cortical monocyte chemotactic protein 1 (1.8-fold) and oxidative DNA marker 8-hydroxy-deoxyguanosine (8-OHdG) (2.4-fold). After 12 weeks, we detected few injected cells, which were localized mostly to the cortical interstitium. Although cell therapy with either hPKC(F+) or hPKC improved renal function, the hPKC(F+) subpopulation provides greater renoprotection, perhaps through attenuation of inflammation and oxidative stress. We conclude that hPKC(F+) may be used as components of cell-based therapies for degenerative kidney diseases.
AB - New therapeutic strategies for chronic kidney disease (CKD) are necessary to offset the rising incidence of CKD and donor shortage. Erythropoietin (EPO), a cytokine produced by fibroblast-like cells in the kidney, has recently emerged as a renoprotective factor with anti-inflammatory, antioxidant properties. This study (a) determined whether human renal cultures (human primary kidney cells [hPKC]) can be enriched in EPO-positive cells (hPKC(F+)) by using magnetic-bead sorting; (b) characterized hPKC(F+) following cell separation; and (c) established that intrarenal delivery of enriched hPKC(F+) cells would be more beneficial in treatment of renal injury, inflammation, and oxidative stress than unsorted hPKC cultures in a chronic kidney injury model. Fluorescence-activated cell sorting analysis revealed higher expression of EPO (36%) and CD73 (27%) in hPKC(F+) as compared with hPKC. After induction of renal injury, intrarenal delivery of hPKC(F+) or hPKC significantly reduced serum creatinine, interstitial fibrosis in the medulla, and abundance of CD68-positive cells in the cortex and medulla (p <. 05). However, only hPKC(F+) attenuated interstitial fibrosis in the renal cortex and decreased urinary albumin (3.5-fold) and urinary tubular injury marker kidney injury molecule 1 (16-fold). hPKC(F+) also significantly reduced levels of renal cortical monocyte chemotactic protein 1 (1.8-fold) and oxidative DNA marker 8-hydroxy-deoxyguanosine (8-OHdG) (2.4-fold). After 12 weeks, we detected few injected cells, which were localized mostly to the cortical interstitium. Although cell therapy with either hPKC(F+) or hPKC improved renal function, the hPKC(F+) subpopulation provides greater renoprotection, perhaps through attenuation of inflammation and oxidative stress. We conclude that hPKC(F+) may be used as components of cell-based therapies for degenerative kidney diseases.
KW - Adult stem cells
KW - Autologous stem cell transplantation
KW - Cell biology
KW - Cellular therapy
KW - Erythropoietin
KW - Renal fibrosis
KW - Tissue-specific stem cells
UR - http://www.scopus.com/inward/record.url?scp=84872116231&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84872116231&partnerID=8YFLogxK
U2 - 10.5966/sctm.2011-0048
DO - 10.5966/sctm.2011-0048
M3 - Article
C2 - 23197816
AN - SCOPUS:84872116231
VL - 1
SP - 373
EP - 383
JO - Stem cells translational medicine
JF - Stem cells translational medicine
SN - 2157-6564
IS - 5
ER -