scholarly journals Current Research of the Renin-Angiotensin System Effect on Stem Cell Therapy

10.5772/67726 ◽  
2017 ◽  
Author(s):  
Elham Ahmadian ◽  
Aziz Eftekhari ◽  
Ahmad Yari Khosroushahi
Keyword(s):  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Renin Angiotensin System ◽  
System Effect ◽  
Angiotensin System ◽  
Renin Angiotensin

Angiotensin II, oxidative stress and stem cell therapy: a matter of delicacy

2015 ◽  
Vol 128 (11) ◽  
pp. 749-750 ◽  
Author(s):  
Anton J.M. Roks
Keyword(s):  
Stem Cell ◽  
Angiotensin Ii ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Renal Injury ◽  
Renin Angiotensin System ◽  
Oxygen Species ◽  
Angiotensin System ◽  
Cell Donor ◽  
Ros Formation

Optimization of stem cell therapy after cardiovascular and renal injury depends on many factors, among which is stem cell donor health. The renin–angiotensin system (RAS) plays an important role in cardiovascular and renal homoeostasis and pathophysiology. It is becoming increasingly clear that the RAS affects the therapeutic performance of stem cells. In this issue of Clinical Science, Kankuri et al. dig deeper into the consequences of excessive angiotensin II signalling and reactive oxygen species (ROS) formation in the stem cell donor, applying a model of regenerative medicine after renal injury.

The Role of the Renin–Angiotensin System in the Cancer Stem Cell Niche

2021 ◽  
pp. 002215542110262
Author(s):  
Ethan J. Kilmister ◽  
Swee T. Tan
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Signaling Pathways ◽  
Renin Angiotensin System ◽  
Epidemiological Data ◽  
Malignant Cells ◽  
Angiotensin System ◽  
Renin Angiotensin

Cancer stem cells (CSCs) drive metastasis, treatment resistance, and tumor recurrence. CSCs reside within a niche, an anatomically distinct site within the tumor microenvironment (TME) that consists of malignant and non-malignant cells, including immune cells. The renin–angiotensin system (RAS), a critical regulator of stem cells and key developmental processes, plays a vital role in the TME. Non-malignant cells within the CSC niche and stem cell signaling pathways such as the Wnt, Hedgehog, and Notch pathways influence CSCs. Components of the RAS and cathepsins B and D that constitute bypass loops of the RAS are expressed on CSCs in many cancer types. There is extensive in vitro and in vivo evidence showing that RAS inhibition reduces tumor growth, cell proliferation, invasion, and metastasis. However, there is inconsistent epidemiological data on the effect of RAS inhibitors on cancer incidence and survival outcomes, attributed to different patient characteristics and methodologies used between studies. Further mechanistic studies are warranted to investigate the precise effects of the RAS on CSCs directly and/or the CSC niche. Targeting the RAS, its bypass loops, and convergent signaling pathways participating in the TME and other key stem cell pathways that regulate CSCs may be a novel approach to cancer treatment:

Expression of Components of the Renin-Angiotensin System by the Embryonic Stem Cell–Like Population within Keloid Lesions

2019 ◽  
Vol 144 (2) ◽  
pp. 372-384 ◽  
Author(s):  
Hugo Humphries ◽  
Helen D. Brasch ◽  
Bede van Schaijik ◽  
Swee T. Tan ◽  
Tinte Itinteang
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin

scholarly journals Characterisation of cancer stem cells and the renin-angiotensin system in colon adenocarcinoma

2021 ◽  
Author(s):  
Matthew Munro
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Lines ◽  
Colon Adenocarcinoma ◽  
Renin Angiotensin System ◽  
Primary Cell ◽  
Low Grade ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Primary Cell Lines

Colorectal cancer (CRC) is the third most common cancer and the second highest cause of cancer deaths globally. More than 70% of CRC-related deaths are due to metastasis to the liver. The cancer stem cell (CSC) concept hypothesises that CSCs drive tumour growth, chemoresistance, recurrence and metastasis. Markers such as CD133, LGR5 and EpCAM, have been used to identify and isolate CSCs in CRC. However, these markers are often expressed by cells with no stem cell properties and are not expressed by all tumour-initiating cells. An improved range of markers to define CSCs is needed. In 2007, adult mouse and human fibroblasts were reprogrammed into a stem cell state and defined as induced pluripotent stem cells (iPSCs) using transcription factors OCT4, SOX2, NANOG, KLF4 and c-MYC. These genes have well-documented roles in embryonic development and the maintenance of pluripotency, and their expression has been investigated in a range of cancers. <br><br>The renin-angiotensin system (RAS) physiologically maintains blood pressure and volume and is also acknowledged to play a role in cancer. Over-expression of (pro)renin receptor (PRR), angiotensin II type 1 receptor (AT1R) and type 2 receptor (AT2R), and angiotensin-converting enzyme (ACE) have been reported in cancer. Epidemiological studies investigating the effect of RAS inhibitors on cancer outcomes have shown contradictory results.<br><br>This thesis investigates the expression of iPSC markers and RAS components in colon adenocarcinoma (CA) with three specific aims: (1) to compare CA-derived primary cell lines to their original CA tissues; (2) to investigate the expression profiles of iPSC markers in CA; and (3) to investigate expression of RAS components by CA CSCs and to determine whether CSCs can be targeted by RAS modulators. <br><br>DNA sequencing was carried out to compare the mutational profiles of formalin-fixed paraffin-embedded (FFPE) CA tissues and CA-derived cell lines to confirm whether the cell lines were a suitable in vitro model for the parent tumours.<br><br><div>Proteomics was performed to determine proteomic differences between CA tissues and patient-matched normal colon (NC) tissues, CA-derived cell lines and NC-derived cells, and between low grade CA (LGCA) tissues and cell lines and high grade CA (HGCA) tissues and cell lines. Biological processes which may link the RAS and CA were investigated, revealing enrichment of various signalling pathways that may play roles in CA onset and progression directly or via the RAS.</div><div><br></div>Western blotting and immunohistochemical staining showed elevated protein levels of OCT4, SOX2, NANOG, c-MYC, AT2R, PRR and cathepsin D in CA tissues relative to their patient-matched NC tissues, with SOX2, ACE and cathepsin B at similar levels and KLF4 less abundant in CA compared with NC tissues. Co-expression analysis by immunofluorescence staining showed a small number of epithelial cells co-expressed NANOG, SOX2, KLF4, c-MYC and CD133, as well as PRR, ACE2 and AT2R, while a small number of stromal cells co-expressed OCT4 and AT2R. This indicates the presence of at least one CSC subpopulation in CA, which expresses RAS components. HGCA tissue-derived cell lines expressed higher levels of OCT4 and SOX2 than LGCA-derived cell lines. The primary cell lines were sorted based on EpCAM expression. These EpCAM High and EpCAM Low cell subpopulations could undergo directed differentiation down the three embryonic lineages. A small number of CA-derived cells, particularly within the HGCA-derived cells, formed tumourspheres. Treatment of HGCA-derived cell lines with RAS modulators revealed that β-blockers and AT2R antagonists consistently reduced their metabolism, tumoursphere formation and iPSC marker expression. <br><br>The findings of this thesis suggest that CA-derived cell lines expressing iPSC markers have stem cell function and express RAS components. Furthermore, RAS modulators may directly influence CSCs in CA by reducing iPSC marker gene expression. This indicates a potential role for RAS modulators in regulating CSCs, which merits further investigation.

scholarly journals Embryonic Stem Cell-Like Population in Dupuytren’s Disease Expresses Components of the Renin-Angiotensin System

2017 ◽  
Vol 5 (7) ◽  
pp. e1422 ◽  
Author(s):  
Nicholas On ◽  
Sabrina P. Koh ◽  
Helen D. Brasch ◽  
Jonathan C. Dunne ◽  
James R. Armstrong ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Renin Angiotensin System ◽  
Dupuytren’S Disease ◽  
Dupuytren's Disease ◽  
Angiotensin System ◽  
Renin Angiotensin

scholarly journals Characterisation of cancer stem cells and the renin-angiotensin system in colon adenocarcinoma

2021 ◽  
Author(s):  
Matthew Munro
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Lines ◽  
Colon Adenocarcinoma ◽  
Renin Angiotensin System ◽  
Primary Cell ◽  
Low Grade ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Primary Cell Lines

Colorectal cancer (CRC) is the third most common cancer and the second highest cause of cancer deaths globally. More than 70% of CRC-related deaths are due to metastasis to the liver. The cancer stem cell (CSC) concept hypothesises that CSCs drive tumour growth, chemoresistance, recurrence and metastasis. Markers such as CD133, LGR5 and EpCAM, have been used to identify and isolate CSCs in CRC. However, these markers are often expressed by cells with no stem cell properties and are not expressed by all tumour-initiating cells. An improved range of markers to define CSCs is needed. In 2007, adult mouse and human fibroblasts were reprogrammed into a stem cell state and defined as induced pluripotent stem cells (iPSCs) using transcription factors OCT4, SOX2, NANOG, KLF4 and c-MYC. These genes have well-documented roles in embryonic development and the maintenance of pluripotency, and their expression has been investigated in a range of cancers. <br><br>The renin-angiotensin system (RAS) physiologically maintains blood pressure and volume and is also acknowledged to play a role in cancer. Over-expression of (pro)renin receptor (PRR), angiotensin II type 1 receptor (AT1R) and type 2 receptor (AT2R), and angiotensin-converting enzyme (ACE) have been reported in cancer. Epidemiological studies investigating the effect of RAS inhibitors on cancer outcomes have shown contradictory results.<br><br>This thesis investigates the expression of iPSC markers and RAS components in colon adenocarcinoma (CA) with three specific aims: (1) to compare CA-derived primary cell lines to their original CA tissues; (2) to investigate the expression profiles of iPSC markers in CA; and (3) to investigate expression of RAS components by CA CSCs and to determine whether CSCs can be targeted by RAS modulators. <br><br>DNA sequencing was carried out to compare the mutational profiles of formalin-fixed paraffin-embedded (FFPE) CA tissues and CA-derived cell lines to confirm whether the cell lines were a suitable in vitro model for the parent tumours.<br><br><div>Proteomics was performed to determine proteomic differences between CA tissues and patient-matched normal colon (NC) tissues, CA-derived cell lines and NC-derived cells, and between low grade CA (LGCA) tissues and cell lines and high grade CA (HGCA) tissues and cell lines. Biological processes which may link the RAS and CA were investigated, revealing enrichment of various signalling pathways that may play roles in CA onset and progression directly or via the RAS.</div><div><br></div>Western blotting and immunohistochemical staining showed elevated protein levels of OCT4, SOX2, NANOG, c-MYC, AT2R, PRR and cathepsin D in CA tissues relative to their patient-matched NC tissues, with SOX2, ACE and cathepsin B at similar levels and KLF4 less abundant in CA compared with NC tissues. Co-expression analysis by immunofluorescence staining showed a small number of epithelial cells co-expressed NANOG, SOX2, KLF4, c-MYC and CD133, as well as PRR, ACE2 and AT2R, while a small number of stromal cells co-expressed OCT4 and AT2R. This indicates the presence of at least one CSC subpopulation in CA, which expresses RAS components. HGCA tissue-derived cell lines expressed higher levels of OCT4 and SOX2 than LGCA-derived cell lines. The primary cell lines were sorted based on EpCAM expression. These EpCAM High and EpCAM Low cell subpopulations could undergo directed differentiation down the three embryonic lineages. A small number of CA-derived cells, particularly within the HGCA-derived cells, formed tumourspheres. Treatment of HGCA-derived cell lines with RAS modulators revealed that β-blockers and AT2R antagonists consistently reduced their metabolism, tumoursphere formation and iPSC marker expression. <br><br>The findings of this thesis suggest that CA-derived cell lines expressing iPSC markers have stem cell function and express RAS components. Furthermore, RAS modulators may directly influence CSCs in CA by reducing iPSC marker gene expression. This indicates a potential role for RAS modulators in regulating CSCs, which merits further investigation.

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