scholarly journals Progress and Challenges of Amniotic Fluid Derived Stem Cells in Therapy of Ischemic Heart Disease

2020 ◽  
Vol 22 (1) ◽  
pp. 102
Author(s):  
Yi-Hsien Fang ◽  
Saprina P. H. Wang ◽  
Hsien-Yuan Chang ◽  
Pei-Jung Yang ◽  
Ping-Yen Liu ◽  
...  

Cardiovascular disease is the leading cause of deaths worldwide, claiming an estimated total of 17.9 million lives each year, of which one-third of the people are under the age of 70 years. Since adult cardiomyocytes fail to regenerate, the heart loses the ability to repair itself after an injury, making patients with heart disease suffer from poor prognosis. Pluripotent stem cells have the ability to differentiate into cardiomyocytes in vitro through a well-established process, which is a new advancement in cardiac regeneration therapy. However, pluripotent stem cell-derived cardiomyocytes have certain drawbacks, such as the risk of arrhythmia and immune incompatibility. Thus, amniotic fluid stem cells (AFSCs), a relatively novel source of stem cells, have been exploited for their ability of pluripotent differentiation. In addition, since AFSCs are weakly positive for the major histocompatibility class II molecules, they may have high immune tolerance. In summary, the possibility of development of cardiomyocytes from AFSCs, as well as their transplantation in host cells to produce mechanical contraction, has been discussed. Thus, this review article highlights the progress of AFSC therapy and its application in the treatment of heart diseases in recent years.

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Mohsin Khan ◽  
Suresh K Verma ◽  
Alexander R Mackie ◽  
Erin Vaughan ◽  
Srikanth Garikipati ◽  
...  

Rationale: Embryonic stem cells (ESCs) hold great promise for cardiac regeneration but are susceptible to ethical concerns, lack of autologous donors and teratoma formation. Recently, it has been observed that beneficial effects of stem cells are mediated by exosomes secreted out under various physiological conditions. ESCs have the ability to produce exosomes however their effect in the context of the heart is unknown. Objective: Determine the effect of ESC derived exosomes for cardiac repair and modulation of CPCs functions in the heart following myocardial infarction. Methods and Results: Exosomes were isolated from murine ESCs (mES Ex) or embryonic fibroblasts (MEFs) by ultracentrifugation and verified by Flotillin-1 immunoblot analysis. Induction of pluripotent markers, survival and in vitro tube formation was enhanced in target cells receiving ESC exosomes indicating therapeutic potential of mES Ex. mES Ex administration resulted in enhanced neovascularization, cardiomyocyte survival and reduced fibrosis post infarction consistent with resurgence of cardiac proliferative response. Importantly, mES Ex mediated considerable enhancement of cardiac progenitor cell (CPC) survival, proliferation and cardiac commitment concurrent with increased c-kit+ CPCs in vivo 4 weeks after mES Ex transfer. miRNA Array analysis of ESC and MEF exosomes revealed significantly high expression of miR290-295 cluster in the ESC exosomes compared to MEF exosomes. The underlying beneficial effect of mES Ex was tied to delivery of ESC miR-294 to the heart and in particular CPCs thereby promoting CPC survival and proliferation as analyzed by FACS based cell death analysis and CyQuant assay respectively. Interestingly, enhanced G1/S transition was observed in CPCs treated with miR-294 in conjunction with significant reduction of G1 phase. Conclusion: In conclusion, mES Ex provide a novel cell free system for cardiac regeneration with the ability to modulate both cardiomyocyte and CPC based repair programs in the heart thereby avoiding the risk of teratoma formation associated with ESCs.


Author(s):  
Binh Yen Nguyen ◽  
Tayyiba Azam ◽  
Xin Wang

Exosomes are a subgroup of extracellular bilayer membrane nanovesicles that are enriched in a variety of bioactive lipids, receptors, transcription factors, surface proteins, DNA and noncoding RNAs. They have been well-recognised to play essential roles in mediating intercellular signalling by delivering bioactive molecules from host cells to regulate the physiological processes of recipient cells. In the context of heart diseases, accumulating studies have indicated that exosome-carried cellular proteins and noncoding RNA derived from different types of cardiac cells, including cardiomyocytes, fibroblasts, endothelial cells, immune cells, adipocytes and resident stem cells have pivotal roles in cardiac remodelling under disease conditions such as cardiac hypertrophy, diabetic cardiomyopathy and MI. In addition, exosomal contents derived from stem cells have been shown to be beneficial for regenerative potential of the heart. In this review, we will discuss current understanding of the role of exosomes in cardiac communication, with a focus on cardiovascular pathophysiology and perspectives for their potential uses as cardiac therapies.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Ekta Minocha ◽  
Rohit Anthony Sinha ◽  
Manali Jain ◽  
Chandra Prakash Chaturvedi ◽  
Soniya Nityanand

Abstract Background We have recently demonstrated that amniotic fluid stem cells (AFSC) express renal progenitor markers and can be differentiated in vitro into renal lineage cell types, viz, juxtaglomerular and renal proximal tubular epithelial-like cells. Here, we have evaluated the therapeutic efficacy of AFSC in a cisplatin-induced rat model of acute renal failure (ARF) and investigated the underlying mechanisms responsible for their renoprotective effects. Methods ARF was induced in Wistar rats by intra-peritoneal injection of cisplatin (7 mg/kg). Five days after cisplatin injection, rats were randomized into two groups and injected with either AFSC or normal saline intravenously. On days 8 and 12 after cisplatin injection, the blood biochemical parameters, histopathological changes, apoptosis and expression of pro-apoptotic, anti-apoptotic, and autophagy-related proteins in renal tissues were studied in both groups of rats. To further confirm whether the protective effects of AFSC on cisplatin-induced apoptosis were dependent on autophagy, chloroquine, an autophagy inhibitor, was administered by the intra-peritoneal route. Results Administration of AFSC in ARF rats resulted in improvement of renal function and attenuation of renal damage as reflected by significant decrease in blood urea nitrogen, serum creatinine levels, tubular cell apoptosis as assessed by Bax/Bcl2 ratio, and expression of the pro-apoptotic proteins, viz, PUMA, Bax, cleaved caspase-3, and cleaved caspase-9, as compared to the saline-treated group. Furthermore, in the AFSC-treated group as compared to the saline-treated group, there was a significant increase in the activation of autophagy as evident by increased expression of LC3-II, ATG5, ATG7, Beclin1, and phospho-AMPK levels with a concomitant decrease in phospho-p70S6K and p62 expression levels. Chloroquine administration led to significant reduction in the anti-apoptotic effects of the AFSC therapy and further deterioration in the renal structure and function caused by cisplatin. Conclusion AFSC led to amelioration of cisplatin-induced ARF which was mediated by inhibition of apoptosis and activation of autophagy. The protective effects of AFSC were blunted by chloroquine, an inhibitor of autophagy, highlighting that activation of autophagy is an important mechanism of action for the protective role of AFSC in cisplatin-induced renal injury.


2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Pasquale Marrazzo ◽  
Cristina Angeloni ◽  
Michela Freschi ◽  
Antonello Lorenzini ◽  
Cecilia Prata ◽  
...  

Amniotic fluid stem cells (AFSCs) are characterized in vivo by a unique niche guarantying their homeostatic role in the body. Maintaining the functionality of stem cells ex vivo for clinical applications requires a continuous improvement of cell culture conditions. Cellular redox status plays an important role in stem cell biology as long as reactive oxygen species (ROS) concentration is finely regulated and their adverse effects are excluded. The aim of this study was to investigate the protective effect of two antioxidants, sulforaphane (SF) and epigallocatechin gallate (EGCG), against in vitro oxidative stress due to hyperoxia and freeze-thawing cycles in AFSCs. Human AFSCs were isolated and characterized from healthy subjects. Assays of metabolic function and antioxidant activity were performed to investigate the effect of SF and EGCG cotreatment on AFSCs. Real-time PCR was used to investigate the effect of the cotreatment on pluripotency, senescence, osteogenic and adipogenic markers, and antioxidant enzymes. Alkaline phosphatase assays and Alizarin Red staining were used to confirm osteogenic differentiation. The cotreatment with SF and EGCG was effective in reducing ROS production, increasing GSH levels, and enhancing the endogenous antioxidant defences through the upregulation of glutathione reductase, NAD(P)H:quinone oxidoreductase-1, and thioredoxin reductase. Intriguingly, the cotreatment sustained the stemness state by upregulating pluripotency markers such as OCT4 and NANOG. Moreover, the cotreatment influenced senescence-associated gene markers in respect to untreated cells. The cotreatment upregulated osteogenic gene markers and promoted osteogenic differentiation in vitro. SF and EGCG can be used in combination in AFSC culture as a strategy to preserve stem cell functionality.


2011 ◽  
Vol 20 (5) ◽  
pp. 643-654 ◽  
Author(s):  
Antonella Poloni ◽  
Giulia Maurizi ◽  
Lucia Babini ◽  
Federica Serrani ◽  
Eleonora Berardinelli ◽  
...  

2013 ◽  
Vol 197 (4) ◽  
pp. 269-282 ◽  
Author(s):  
Yu Zhou ◽  
David L. Mack ◽  
J. Koudy Williams ◽  
Sayed-Hadi Mirmalek-Sani ◽  
Emily Moorefield ◽  
...  

2014 ◽  
Vol 10 (5) ◽  
pp. 712-724 ◽  
Author(s):  
B. Rossi ◽  
B. Merlo ◽  
S. Colleoni ◽  
E. Iacono ◽  
P. L. Tazzari ◽  
...  

2013 ◽  
Vol 45 (8) ◽  
pp. 669-676 ◽  
Author(s):  
Gianluca Carnevale ◽  
Massimo Riccio ◽  
Alessandra Pisciotta ◽  
Francesca Beretti ◽  
Tullia Maraldi ◽  
...  

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Tullia Maraldi ◽  
Marianna Guida ◽  
Manuela Zavatti ◽  
Elisa Resca ◽  
Laura Bertoni ◽  
...  

Human amniotic fluid stem cells (AFSC) are an attractive source for cell therapy due to their multilineage differentiation potential and accessibility advantages. However the clinical application of human stem cells largely depends on their capacity to expandin vitro, since there is an extensive donor-to-donor heterogeneity. Reactive oxygen species (ROS) and cellular oxidative stress are involved in many physiological and pathophysiological processes of stem cells, including pluripotency, proliferation, differentiation, and stress resistance. The mode of action of ROS is also dependent on the localization of their target molecules. Thus, the modifications induced by ROS can be separated depending on the cellular compartments they affect. NAD(P)H oxidase family, particularly Nox4, has been known to produce ROS in the nucleus. In the present study we show that Nox4 nuclear expression (nNox4) depends on the donor and it correlates with the expression of transcription factors involved in stemness regulation, such as Oct4, SSEA-4, and Sox2. Moreover nNox4 is linked with the nuclear localization of redox sensitive transcription factors, as Nrf2 and NF-κB, and with the differentiation potential. Taken together, these results suggest that nNox4 regulation may have important effects in stem cell capability through modulation of transcription factors and DNA damage.


2008 ◽  
Vol 26 (3) ◽  
pp. 269-270 ◽  
Author(s):  
Mauro Toselli ◽  
Elisabetta Cerbai ◽  
Ferdinando Rossi ◽  
Elena Cattaneo
Keyword(s):  

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