Abstract
Progenitor/stem cell-based kidney regenerative strategies are a key step towards the development of novel therapeutic regimens for kidney disease treatment. However, the route of cell delivery, e.g., intravenous, intra-arterial, or intra-parenchymal, may affect the efficiency for kidney repair in different models of acute and chronic injury. Here, we describe a protocol of intra-aorta progenitor/stem cell injection in rats following either acute ischemia-reperfusion injury or acute proteinuria induced by puromycin aminonucleoside (PAN) – the experimental prototype of human minimal change disease and early stages of focal and segmental glomerulosclerosis. Vascular clips were applied across both renal pedicles for 35 min, or a single dose of PAN was injected via intra-peritoneal route, respectively. Subsequently, 2 x 106 stem cells [green fluorescent protein (GFP)-labeled c-Kit+ progenitor/stem cells or GFP-mesenchymal stem cells] or saline were injected into the suprarenal aorta, above the renal arteries, after application of a vascular clip to the abdominal aorta below the renal arteries. This approach contributed to engraftment rates of ∼10% at day 8 post ischemia-reperfusion injury, when c-Kit+ progenitor/stem cells were injected, which accelerated kidney recovery. Similar rates of engraftment were found after PAN-induced podocyte damage at day 21. With practice and gentle surgical technique, 100% of the rats could be injected successfully, and, in the week following injection, ∼ 85% of the injected rats will recover completely. Given the similarities in mammals, much of the data obtained from intra-arterial delivery of progenitor/stem cells in rodents can be tested in translational research and clinical trials with endovascular catheters in humans.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1390-1403 |
| Number of pages | 14 |
| Journal | Cell Transplantation |
| Volume | 28 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 1 2019 |
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Keywords
- acute kidney injury
- acute proteinuria
- engraftment
- ischemia-reperfusion injury
- progenitor/stem cells
- surgical technique
ASJC Scopus subject areas
- Biomedical Engineering
- Cell Biology
- Transplantation
Cite this
Progenitor/Stem Cell Delivery by Suprarenal Aorta Route in Acute Kidney Injury. / Rangel, Érika B.; Gomes, Samirah A.; Kanashiro-Takeuchi, Rosemeire; Hare, Joshua M.
In: Cell Transplantation, Vol. 28, No. 11, 01.11.2019, p. 1390-1403.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Progenitor/Stem Cell Delivery by Suprarenal Aorta Route in Acute Kidney Injury
AU - Rangel, Érika B.
AU - Gomes, Samirah A.
AU - Kanashiro-Takeuchi, Rosemeire
AU - Hare, Joshua M.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Progenitor/stem cell-based kidney regenerative strategies are a key step towards the development of novel therapeutic regimens for kidney disease treatment. However, the route of cell delivery, e.g., intravenous, intra-arterial, or intra-parenchymal, may affect the efficiency for kidney repair in different models of acute and chronic injury. Here, we describe a protocol of intra-aorta progenitor/stem cell injection in rats following either acute ischemia-reperfusion injury or acute proteinuria induced by puromycin aminonucleoside (PAN) – the experimental prototype of human minimal change disease and early stages of focal and segmental glomerulosclerosis. Vascular clips were applied across both renal pedicles for 35 min, or a single dose of PAN was injected via intra-peritoneal route, respectively. Subsequently, 2 x 106 stem cells [green fluorescent protein (GFP)-labeled c-Kit+ progenitor/stem cells or GFP-mesenchymal stem cells] or saline were injected into the suprarenal aorta, above the renal arteries, after application of a vascular clip to the abdominal aorta below the renal arteries. This approach contributed to engraftment rates of ∼10% at day 8 post ischemia-reperfusion injury, when c-Kit+ progenitor/stem cells were injected, which accelerated kidney recovery. Similar rates of engraftment were found after PAN-induced podocyte damage at day 21. With practice and gentle surgical technique, 100% of the rats could be injected successfully, and, in the week following injection, ∼ 85% of the injected rats will recover completely. Given the similarities in mammals, much of the data obtained from intra-arterial delivery of progenitor/stem cells in rodents can be tested in translational research and clinical trials with endovascular catheters in humans.
AB - Progenitor/stem cell-based kidney regenerative strategies are a key step towards the development of novel therapeutic regimens for kidney disease treatment. However, the route of cell delivery, e.g., intravenous, intra-arterial, or intra-parenchymal, may affect the efficiency for kidney repair in different models of acute and chronic injury. Here, we describe a protocol of intra-aorta progenitor/stem cell injection in rats following either acute ischemia-reperfusion injury or acute proteinuria induced by puromycin aminonucleoside (PAN) – the experimental prototype of human minimal change disease and early stages of focal and segmental glomerulosclerosis. Vascular clips were applied across both renal pedicles for 35 min, or a single dose of PAN was injected via intra-peritoneal route, respectively. Subsequently, 2 x 106 stem cells [green fluorescent protein (GFP)-labeled c-Kit+ progenitor/stem cells or GFP-mesenchymal stem cells] or saline were injected into the suprarenal aorta, above the renal arteries, after application of a vascular clip to the abdominal aorta below the renal arteries. This approach contributed to engraftment rates of ∼10% at day 8 post ischemia-reperfusion injury, when c-Kit+ progenitor/stem cells were injected, which accelerated kidney recovery. Similar rates of engraftment were found after PAN-induced podocyte damage at day 21. With practice and gentle surgical technique, 100% of the rats could be injected successfully, and, in the week following injection, ∼ 85% of the injected rats will recover completely. Given the similarities in mammals, much of the data obtained from intra-arterial delivery of progenitor/stem cells in rodents can be tested in translational research and clinical trials with endovascular catheters in humans.
KW - acute kidney injury
KW - acute proteinuria
KW - engraftment
KW - ischemia-reperfusion injury
KW - progenitor/stem cells
KW - surgical technique
UR - http://www.scopus.com/inward/record.url?scp=85073578507&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85073578507&partnerID=8YFLogxK
U2 - 10.1177/0963689719860826
DO - 10.1177/0963689719860826
M3 - Article
C2 - 31409111
AN - SCOPUS:85073578507
VL - 28
SP - 1390
EP - 1403
JO - Cell Transplantation
JF - Cell Transplantation
SN - 0963-6897
IS - 11
ER -