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.
N1 - Funding Information:
https://orcid.org/0000-0003-0982-2484 Rangel Érika B. 1 2 3 Gomes Samirah A. 1 4 Kanashiro-Takeuchi Rosemeire 1 5 Hare Joshua M. 1 5 6 1 Interdisciplinary Stem Cell Institute, Leonard M Miller School of Medicine, University of Miami, USA 2 Hospital Israelita Albert Einstein, São Paulo, Brazil 3 Federal University of São Paulo, Brazil 4 Laboratory of Cellular, Genetic, and Molecular Nephrology, Renal Division, University of São Paulo, Brazil 5 Department of Molecular and Cellular Pharmacology, Leonard M Miller School of Medicine, University of Miami, USA 6 Division of Cardiology, Leonard M Miller School of Medicine, University of Miami, USA Érika B. Rangel, Interdisciplinary Stem Cell Institute, Biomedical Research Building, University of Miami, 1501NW Tenth Ave, Room 832, Miami, FL, 33136, USA. Email: erikabr@uol.com.br 11 2019 28 11 1390 1403 2 3 2019 14 5 2019 3 6 2019 © The Author(s) 2019 2019 SAGE Publications Inc, unless otherwise noted. Manuscript content on this site is licensed under Creative Commons Licenses This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/ ) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage ). 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 10 6 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. progenitor/stem cells acute kidney injury ischemia-reperfusion injury acute proteinuria engraftment surgical technique National Institutes of Health RO1 grants HL107110 and AG025017 Ethical Approval Ethical approval to perform surgical and experimental protocols were obtained from Institutional Animal Care and Use Committees (IACUC) of the University of Miami (number 10–176, Leonard M Miller School of Medicine, University of Miami, FL, USA). Statement of Human and Animal Rights All procedures in this study were conducted in accordance with the institutional guidelines of University of Miami, FL, USA, that are in compliance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Statement of Informed Consent There are no human subjects in this article and informed consent is not applicable. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Funding The author(s) disclosed receipt of the following financial support for the research and/or authorship of this article: This work was supported by a postdoctoral research fellowship grant (1KD07-33958) from the James and Esther King Florida Biomedical Research Program to E.B.R., and National Institutes of Health RO1 grants HL107110 and AG025017 to J.M.H. ORCID iD Érika B Rangel https://orcid.org/0000-0003-0982-2484 Supplemental Material Supplemental material for this article is available online.
Publisher Copyright:
© The Author(s) 2019.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
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
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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 -
