scholarly journals The Systems Biology of Stem Cell Released Molecules—Based Therapeutics

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Greg Maguire ◽  
Peter Friedman

Most therapeutics are based on the traditional method of reductionism where a clinically defined condition is broken down into a defined biochemical pathway underlying the condition, then a target in the pathway is identified, followed by developing a drug to interact with the target, modifying the target such that the disease is ameliorated. Biology acts as a system, therefore reductionist approaches to developing therapeutics are limited in therapeutic value because disease or traumatized tissue involves multiple underlying pathways, only a part of the pathways underlying the disease is manipulated by the traditional therapeutic. Much data regarding stem cells shows that their beneficial effects are not restricted to their ability to differentiate, but is more likely due in large part to their ability to release a multitude of molecules. Stem cells release potent combinations of factors that modulate the composition of the cellular milieu to evoke a multitude of responses from neighboring cells. Therefore, stem cells represent a natural systems-based biological factory for the production and release of a multitude of molecules that interact with the system of biomolecular circuits underlying an indication. Current research includes efforts to define, stimulate, enhance, and harness stem cell released molecules (SRM) to develop systems-therapeutics.

2021 ◽  
Vol 22 (4) ◽  
pp. 1824
Author(s):  
Matthias Mietsch ◽  
Rabea Hinkel

With cardiovascular diseases affecting millions of patients, new treatment strategies are urgently needed. The use of stem cell based approaches has been investigated during the last decades and promising effects have been achieved. However, the beneficial effect of stem cells has been found to being partly due to paracrine functions by alterations of their microenvironment and so an interesting field of research, the “stem- less” approaches has emerged over the last years using or altering the microenvironment, for example, via deletion of senescent cells, application of micro RNAs or by modifying the cellular energy metabolism via targeting mitochondria. Using autologous muscle-derived mitochondria for transplantations into the affected tissues has resulted in promising reports of improvements of cardiac functions in vitro and in vivo. However, since the targeted treatment group represents mainly elderly or otherwise sick patients, it is unclear whether and to what extent autologous mitochondria would exert their beneficial effects in these cases. Stem cells might represent better sources for mitochondria and could enhance the effect of mitochondrial transplantations. Therefore in this review we aim to provide an overview on aging effects of stem cells and mitochondria which might be important for mitochondrial transplantation and to give an overview on the current state in this field together with considerations worthwhile for further investigations.


2013 ◽  
Vol 41 (1) ◽  
pp. 283-287 ◽  
Author(s):  
Giovanni Camussi ◽  
Maria Chiara Deregibus ◽  
Vincenzo Cantaluppi

The paracrine theory has recently changed the view of the biological action of stem cells and of the subsequent potential application of stem cells in regenerative medicine. Indeed, most of the beneficial effects of stem-cell-based therapy have been attributed to soluble factors released from stem cells. In this context, MVs (microvesicles) released as exosomes from the endosomal compartment, or as shedding vesicles from the cell surface, may play a relevant role in the intercellular communication between stem and injured cells. By transferring proteins, bioactive lipids, mRNA and microRNA, MVs act as vehicles of information that may lead to alteration of the phenotype of recipient cells. The exchange of information between stem cells and tissue-injured cells is reciprocal. The MV-mediated transfer of tissue-specific information from the injured cells to stem cells may reprogramme the latter to gain phenotypic and functional characteristics of the cell of origin. On the other hand, MVs released from stem cells may confer a stem-cell-like phenotype to injured cells, with the consequent activation of self-regenerative programmes. In fact, MVs released from stem cells retain several biological activities that are able to reproduce the beneficial effects of stem cells in a variety of experimental models.


2014 ◽  
Vol 23 (10) ◽  
pp. 1279-1291 ◽  
Author(s):  
Yaohui Tang ◽  
Beibei Cai ◽  
Falei Yuan ◽  
Xiaosong He ◽  
Xiaojie Lin ◽  
...  

Mesenchymal stem cell (MSC) transplantation has been shown to be beneficial in treating cerebral ischemia. However, such benefit is limited by the low survival of transplanted MSCs in an ischemic microenvironment. Previous studies showed that melatonin pretreatment can increase MSC survival in the ischemic kidney. However, whether it will improve MSC survival in cerebral ischemia is unknown. Our study examined the effect of melatonin pretreatment on MSCs under ischemia-related conditions in vitro and after transplantation into ischemic rat brain. Results showed that melatonin pretreatment greatly increased survival of MSCs in vitro and reduced their apoptosis after transplantation into ischemic brain. Melatonin-treated MSCs (MT-MSCs) further reduced brain infarction and improved neurobehavioral outcomes. Angiogenesis, neurogenesis, and the expression of vascular endothelial growth factor (VEGF) were greatly increased in the MT-MSC-treated rats. Melatonin treatment increased the level of p-ERK1/2 in MSCs, which can be blocked by the melatonin receptor antagonist luzindole. ERK phosphorylation inhibitor U0126 completely reversed the protective effects of melatonin, suggesting that melatonin improves MSC survival and function through activating the ERK1/2 signaling pathway. Thus, stem cells pretreated by melatonin may represent a feasible approach for improving the beneficial effects of stem cell therapy for cerebral ischemia.


2016 ◽  
Vol 2016 ◽  
pp. 1-20 ◽  
Author(s):  
Bryan Holvoet ◽  
Liesbeth De Waele ◽  
Mattia Quattrocelli ◽  
Olivier Gheysens ◽  
Maurillio Sampaolesi ◽  
...  

Numerous neurodegenerative and neuromuscular disorders are associated with cell-specific depletion in the human body. This imbalance in tissue homeostasis is in healthy individuals repaired by the presence of endogenous stem cells that can replace the lost cell type. However, in most disorders, a genetic origin or limited presence or exhaustion of stem cells impairs correct cell replacement. During the last 30 years, methods to readily isolate and expand stem cells have been developed and this resulted in a major change in the regenerative medicine field as it generates sufficient amount of cells for human transplantation applications. Furthermore, stem cells have been shown to release cytokines with beneficial effects for several diseases. At present however, clinical stem cell transplantations studies are struggling to demonstrate clinical efficacy despite promising preclinical results. Therefore, to allow stem cell therapy to achieve its full potential, more insight in theirin vivobehavior has to be achieved. Different methods to noninvasively monitor these cells have been developed and are discussed. In some cases, stem cell monitoring even reached the clinical setting. We anticipate that by further exploring these imaging possibilities and unraveling theirin vivobehavior further improvement in stem cell transplantations will be achieved.


2012 ◽  
Vol 90 (10) ◽  
pp. 1335-1344 ◽  
Author(s):  
Forum Kamdar ◽  
Mohammad Nurulqadr Jameel ◽  
Paul Score ◽  
Jianyi Zhang

Cellular transplantation for cardiac repair has emerged as an exciting treatment option for patients with myocardial infarction (MI) and heart failure. Animal models of post-infarction left ventricular remodeling have demonstrated an improvement in left ventricular (LV) function, decrease in scar size, and amelioration of adverse cardiac remodeling after stem cell transplantation. These beneficial effects occur despite minimal engraftment and negligible differentiation of transplanted cells. Evidence of the heart capability to self-renew continues to mount; however, the extent to which this occurs is still unclear. Although there is a specific population of cardiac stem cells capable of differentiating into cardiomyocytes, they alone are not capable of fully regenerating tissue damaged by MI. Therefore, paracrine mechanisms may be responsible for activating endogenous stem cells to promote regeneration and prevent apoptosis. These structural beneficial effects may reduce regional wall stresses, consequently leading to long-term host myocardium gene/protein expression changes, which may subsequently result in improvement in LV function.


2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Paula Müller ◽  
Natalia Voronina ◽  
Frauke Hausburg ◽  
Cornelia A. Lux ◽  
Frank Wiekhorst ◽  
...  

Aim. CD133+stem cells bear huge potential for regenerative medicine. However, low retention in the injured tissue and massive cell death reduce beneficial effects. In order to address these issues, we intended to develop a nonviral system for appropriate cell engineering.Materials and Methods. Modification of human CD133+stem cells with magnetic polyplexes carrying microRNA was studied in terms of efficiency, safety, and targeting potential.Results. High microRNA uptake rates (~80–90%) were achieved without affecting CD133+stem cell properties. Modified cells can be magnetically guided.Conclusion. We developed a safe and efficient protocol for CD133+stem cell modification. Our work may become a basis to improve stem cell therapeutical effects as well as their monitoring with magnetic resonance imaging.


2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Sara Shaban ◽  
Mostafa Wanees Ahmed El-Husseny ◽  
Abdelrahman Ibrahim Abushouk ◽  
Amr Muhammad Abdo Salem ◽  
Mediana Mamdouh ◽  
...  

Although physiological levels of reactive oxygen species (ROS) are required to maintain the self-renewal capacity of stem cells, elevated ROS levels can induce chromosomal aberrations, mitochondrial DNA damage, and defective stem cell differentiation. Over the past decade, several studies have shown that antioxidants can not only mitigate oxidative stress and improve stem cell survival but also affect the potency and differentiation of these cells. Further beneficial effects of antioxidants include increasing genomic stability, improving the adhesion of stem cells to culture media, and enabling researchers to manipulate stem cell proliferation by using different doses of antioxidants. These findings can have several clinical implications, such as improving neurogenesis in patients with stroke and neurodegenerative diseases, as well as improving the regeneration of infarcted myocardial tissue and the banking of spermatogonial stem cells. This article reviews the cellular and molecular effects of antioxidant supplementation to cultured or transplanted stem cells and draws up recommendations for further research in this area.


Biology ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 596
Author(s):  
Farah Al-Yassir ◽  
Ghalia Khoder ◽  
Subi Sugathan ◽  
Prashanth Saseedharan ◽  
Asma Al Menhali ◽  
...  

Patients with gastric mucosal erosions are predisposed to chronic gastritis, ulcer or even cancer. The repair of mucosal erosions involves several events including proliferation of gastric epithelial stem cells. The aim of this study was to investigate the effects of the probiotic mixture of De Simone Formulation on gastric epithelial stem cell lineages in mouse models of gastric mucosal erosions. Gastric erosions were induced by a single oral gavage of 80% ethanol containing 15 mg/mL acetylsalicylic acid (5 mL/kg) following a daily dose of probiotic mixture (5 mg/day/mouse) for 10 days. In another protocol, erosions were induced by a daily gavage of acetylsalicylic acid (400 mg/kg/day/mouse) for 5 days before or after daily administration of probiotic mixture for 5 days. Control mice received water gavage for 10 days. All mice were injected with bromodeoxyuridine two hours before sacrifice to label S-phase cells. The stomachs of all mice were processed for histological examination, lectin binding, and immunohistochemical analysis. The results reveal that mice that received probiotics before or after the induction of erosion showed a decrease in erosion index with an increase in gastric epithelial stem/progenitor cell proliferation and enhanced production of mucus, trefoil factors, and ghrelin by mucous and enteroendocrine cell lineages. These mice also showed restoration of the amount of H+,K+-ATPase and pepsinogen involved in the production of the harsh acidic environment by parietal and chief cell lineages. In conclusion, this study demonstrates the beneficial effects of probiotics against gastric mucosal erosion and highlights the involvement and modulation of proliferative stem cells and their multiple glandular epithelial cell lineages.


Neurotrauma ◽  
2018 ◽  
pp. 431-444
Author(s):  
Ping Wu ◽  
Mingliang Yang ◽  
Yan Hao ◽  
Shiqing Feng ◽  
Jianjun Li

Traumatic spinal cord injury (SCI), a devastating disorder that severely affects the quality of life in patients, currently lacks effective therapies. Stem cell research offers a promising option to facilitate spinal cord repair. This chapter provides an overview of the major types of stem cells being used in preclinical animal studies and clinical trials to treat SCI, including mesenchymal, neural, hematopoietic, embryonic, and induced pluripotent stem cells. The authors summarize the beneficial effects of stem cells as a potential new therapeutic approach, but also raise the concerns of the limitation and challenges the field is facing, and suggest future directions.


2014 ◽  
Vol 2014 ◽  
pp. 1-17 ◽  
Author(s):  
Lei Hao ◽  
Zhongmin Zou ◽  
Hong Tian ◽  
Yubo Zhang ◽  
Huchuan Zhou ◽  
...  

In recent years, stem cell-based approaches have attracted more attention from scientists and clinicians due to their possible therapeutical effect on stroke. Animal studies have demonstrated that the beneficial effects of stem cells including embryonic stem cells (ESCs), inducible pluripotent stem cells (iPSCs), neural stem cells (NSCs), and mesenchymal stem cell (MSCs) might be due to cell replacement, neuroprotection, endogenous neurogenesis, angiogenesis, and modulation on inflammation and immune response. Although several clinical studies have shown the high efficiency and safety of stem cell in stroke management, mainly MSCs, some issues regarding to cell homing, survival, tracking, safety, and optimal cell transplantation protocol, such as cell dose and time window, should be addressed. Undoubtably, stem cell-based gene therapy represents a novel potential therapeutic strategy for stroke in future.


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