Pre-eclampsia, the development of hypertension and proteinuria or end-organ damage during pregnancy, is a leading cause of both maternal and fetal morbidity and mortality, and there are no effective clinical treatments for pre-eclampsia aside from delivery. The development of pre-eclampsia is characterized by maladaptation of the maternal immune system, excessive inflammation and endothelial dysfunction. We have reported that detection of extracellular RNA by the Toll-like receptors (TLRs) 3 and 7 is a key initiating signal that contributes to the development of pre-eclampsia. PLacental eXpanded (PLX-PAD) cells are human placenta-derived, mesenchymal-like, adherent stromal cells that have anti-inflammatory, proangiogenic, cytoprotective and regenerative properties, secondary to paracrine secretion of various molecules in response to environmental stimulation. We hypothesized that PLX-PAD cells would reduce the associated inflammation and tissue damage and lower blood pressure in mice with pre-eclampsia induced by TLR3 or TLR7 activation. Injection of PLX-PAD cells on gestational day 14 significantly decreased systolic blood pressure by day 17 in TLR3-induced and TLR7-induced hypertensive mice (TLR3 144–111 mmHg; TLR7 145–106 mmHg; both P<0.05), and also normalized their elevated urinary protein:creatinine ratios (TLR3 5.68–3.72; TLR7 5.57–3.84; both P<0.05). On gestational day 17, aortic endothelium-dependent relaxation responses improved significantly in TLR3-induced and TLR7-induced hypertensive mice that received PLX-PAD cells on gestational day 14 (TLR3 35–65%; TLR7 37–63%; both P<0.05). In addition, markers of systemic inflammation and placental injury, increased markedly in both groups of TLR-induced hypertensive mice, were reduced by PLX-PAD cells. Importantly, PLX-PAD cell therapy had no effects on these measures in pregnant control mice or on the fetuses. These data demonstrate that PLX-PAD cell therapy can safely reverse pre-eclampsia-like features during pregnancy and have a potential therapeutic role in pre-eclampsia treatment.
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Radiation nephropathy is mitigated by EET-A and also by captopril. The severe histological injury of radiation nephropathy includes cast formation and mesangiolysis. Both are significantly attenuated by EET-A or captopril. PAS stained kidney, 200x magnification. For further details see pp. 587–599. Image kindly provided by Dr. Md Abdul Hye Khan.
Research Article|
February 17 2016
Human placenta-derived stromal cells decrease inflammation, placental injury and blood pressure in hypertensive pregnant mice
Piyali Chatterjee;
Piyali Chatterjee
*Department of Internal Medicine, Division of Nephrology and Hypertension, Texas A&M Health Science Center/Baylor Scott & White Health, 702 SW HK Dodgen Loop, Temple, TX, U.S.A.
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Valorie L. Chiasson;
Valorie L. Chiasson
*Department of Internal Medicine, Division of Nephrology and Hypertension, Texas A&M Health Science Center/Baylor Scott & White Health, 702 SW HK Dodgen Loop, Temple, TX, U.S.A.
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Lena Pinzur;
Lena Pinzur
†Pluristem Therapeutics Inc., Haifa 31905, Israel
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Shani Raveh;
Shani Raveh
†Pluristem Therapeutics Inc., Haifa 31905, Israel
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Eytan Abraham;
Eytan Abraham
†Pluristem Therapeutics Inc., Haifa 31905, Israel
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Kathleen A. Jones;
Kathleen A. Jones
‡Department of Pathology, Texas A&M Health Science Center/Baylor Scott & White Health, Temple, TX, U.S.A.
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Kelsey R. Bounds;
Kelsey R. Bounds
*Department of Internal Medicine, Division of Nephrology and Hypertension, Texas A&M Health Science Center/Baylor Scott & White Health, 702 SW HK Dodgen Loop, Temple, TX, U.S.A.
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Racheli Ofir;
Racheli Ofir
†Pluristem Therapeutics Inc., Haifa 31905, Israel
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Liat Flaishon;
Liat Flaishon
†Pluristem Therapeutics Inc., Haifa 31905, Israel
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Ayelet Chajut;
Ayelet Chajut
†Pluristem Therapeutics Inc., Haifa 31905, Israel
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Brett M. Mitchell
*Department of Internal Medicine, Division of Nephrology and Hypertension, Texas A&M Health Science Center/Baylor Scott & White Health, 702 SW HK Dodgen Loop, Temple, TX, U.S.A.
Correspondence: B. Mitchell (email bmitchell@tamhsc.edu).
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Publisher: Portland Press Ltd
Received:
August 10 2015
Revision Received:
December 16 2015
Accepted:
December 18 2015
Accepted Manuscript online:
December 18 2015
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 Authors; published by Portland Press Limited
2016
Clin Sci (Lond) (2016) 130 (7): 513–523.
Article history
Received:
August 10 2015
Revision Received:
December 16 2015
Accepted:
December 18 2015
Accepted Manuscript online:
December 18 2015
Citation
Piyali Chatterjee, Valorie L. Chiasson, Lena Pinzur, Shani Raveh, Eytan Abraham, Kathleen A. Jones, Kelsey R. Bounds, Racheli Ofir, Liat Flaishon, Ayelet Chajut, Brett M. Mitchell; Human placenta-derived stromal cells decrease inflammation, placental injury and blood pressure in hypertensive pregnant mice. Clin Sci (Lond) 1 April 2016; 130 (7): 513–523. doi: https://doi.org/10.1042/CS20150555
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