Therapeutic potential of stem cells for preterm infant brain damage: Can we move from the heterogeneity of preclinical and clinical studies to established therapeutics?

2021 ◽  
Vol 186 ◽  
pp. 114461
Author(s):  
Sofia Passera ◽  
Marta Boccazzi ◽  
Cindy Bokobza ◽  
Valerie Faivre ◽  
Fabio Mosca ◽  
...  
Keyword(s):  
Stem Cells ◽  
Preterm Infant ◽  
Brain Damage ◽  
Clinical Studies ◽  
Therapeutic Potential ◽  
Infant Brain ◽  
Preclinical And Clinical Studies

scholarly journals Exosomes contribution in COVID-19 patients’ treatment

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Loubna Mazini ◽  
Luc Rochette ◽  
Gabriel Malka
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Clinical Studies ◽  
Transforming Growth Factor ◽  
Therapeutic Potential ◽  
Therapeutic Option ◽  
Endogenous Factors ◽  
Insulin Growth Factor ◽  
Preclinical And Clinical Studies ◽  
Endothelial Growth Factor

AbstractAdipose cell-free derivatives have been recently gaining attention as potential therapeutic agents for various human diseases. In this context, mesenchymal stromal/stem cells (MSCs), adipocyte mesenchymal stem cells (Ad-MSCs) and adipose-derived stem cells (ADSC) possessing potent immunomodulatory activities are proposed as a therapeutic option for the treatment of coronavirus disease 2019 (COVID-19). The COVID-19 represents a global concern of public health caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in which there is not actually any specific therapy. MSCs exert an immunomodulation effect due to the secretion of endogenous factors, such as vascular endothelial growth factor (VEGF), insulin growth factor (IGF), and nerve growth factor (NGF), transforming growth factor (TGF)-β and growth differentiation factor (GDF)-11. Recent reports are promising for further studies and clinical applications of ADSCs and Ad-MSCs in COVID-19 patients. Experimental and clinical studies are exploring the therapeutic potential of both MSCs and derived-exosomes in moderating the morbidity and mortality of COVID-19. In this field, more preclinical and clinical studies are warranted to find an effective treatment for the patients suffering from COVID-19 infection.

scholarly journals A Review of Placenta and Umbilical Cord-Derived Stem Cells and the Immunomodulatory Basis of Their Therapeutic Potential in Bronchopulmonary Dysplasia

2021 ◽  
Vol 9 ◽  
Author(s):  
Wai Kit Chia ◽  
Fook Choe Cheah ◽  
Nor Haslinda Abdul Aziz ◽  
Nirmala Chandralega Kampan ◽  
Salwati Shuib ◽  
...  
Keyword(s):  
Stem Cells ◽  
Umbilical Cord ◽  
Bronchopulmonary Dysplasia ◽  
Therapeutic Potential ◽  
Therapeutic Agents ◽  
Lung Disorder ◽  
Routes Of Administration ◽  
Injured Lung ◽  
Preclinical And Clinical Studies ◽  
Modern Era

Bronchopulmonary dysplasia (BPD) is a devastating lung disorder of preterm infants as a result of an aberrant reparative response following exposures to various antenatal and postnatal insults. Despite sophisticated medical treatment in this modern era, the incidence of BPD remains unabated. The current strategies to prevent and treat BPD have met with limited success. The emergence of stem cell therapy may be a potential breakthrough in mitigating this complex chronic lung disorder. Over the last two decades, the human placenta and umbilical cord have gained increasing attention as a highly potential source of stem cells. Placenta-derived stem cells (PDSCs) and umbilical cord-derived stem cells (UCDSCs) display several advantages such as immune tolerance and are generally devoid of ethical constraints, in addition to their stemness qualities. They possess the characteristics of both embryonic and mesenchymal stromal/stem cells. Recently, there are many preclinical studies investigating the use of these cells as therapeutic agents in neonatal disease models for clinical applications. In this review, we describe the preclinical and clinical studies using PDSCs and UCDSCs as treatment in animal models of BPD. The source of these stem cells, routes of administration, and effects on immunomodulation, inflammation and regeneration in the injured lung are also discussed. Lastly, a brief description summarized the completed and ongoing clinical trials using PDSCs and UCDSCs as therapeutic agents in preventing or treating BPD. Due to the complexity of BPD, the development of a safe and efficient therapeutic agent remains a major challenge to both clinicians and researchers.

scholarly journals The role of the metabotropic glutamate receptor 5 in nicotine addiction

CNS Spectrums ◽  
2020 ◽  
pp. 1-6
Author(s):  
Funda Akkus ◽  
Sylvia Terbeck ◽  
Connor J. Haggarty ◽  
Valerie Treyer ◽  
Janan J. Dietrich ◽  
...  
Keyword(s):  
Glutamate Receptor ◽  
Clinical Studies ◽  
Metabotropic Glutamate Receptor ◽  
Therapeutic Potential ◽  
Nicotine Addiction ◽  
Metabotropic Glutamate Receptor 5 ◽  
Metabotropic Glutamate ◽  
Nicotine Abuse ◽  
Preclinical And Clinical Studies

Abstract This review summarizes the evidence for the potential involvement of metabotropic glutamate receptor 5 (mGluR5) in the development of nicotine addiction. Nicotine is consumed worldwide and is highly addictive. Previous research has extensively investigated the role of dopamine in association with reward learning and addiction, which has provided strong evidence for the involvement of dopaminergic neuronal circuitry in nicotine addiction. More recently, researchers focused on glutamatergic transmission after nicotine abuse, and its involvement in the reinforcing and rewarding effects of nicotine addiction. A number of robust preclinical and clinical studies have shown mGluR5 signaling as a facilitating mechanism of nicotine addiction and nicotine withdrawal. Specifically, clinical studies have illustrated lower cortical mGluR5 density in smokers compared to nonsmokers in the human brain. In addition, mGluR5 might selectively regulate craving and withdrawal. This suggests that mGluR5 could be a key receptor in the development of nicotine addiction and therefore clinical trials to examine the therapeutic potential of mGluR5 agents could help to contribute to reduce nicotine addiction in society.

scholarly journals Cell Adhesion and Long-Term Survival of Transplanted Mesenchymal Stem Cells: A Prerequisite for Cell Therapy

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Seahyoung Lee ◽  
Eunhyun Choi ◽  
Min-Ji Cha ◽  
Ki-Chul Hwang
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Adhesion ◽  
Therapeutic Potential ◽  
Term Survival ◽  
Differentiation Potential ◽  
Cell Therapies ◽  
Beneficial Effects ◽  
Genetic Modifications ◽  
Preclinical And Clinical Studies

The literature provides abundant evidence that mesenchymal stem cells (MSCs) are an attractive resource for therapeutics and have beneficial effects in regenerating injured tissues due to their self-renewal ability and broad differentiation potential. Although the therapeutic potential of MSCs has been proven in both preclinical and clinical studies, several questions have not yet been addressed. A major limitation to the use of MSCs in clinical applications is their poor viability at the site of injury due to the harsh microenvironment and to anoikis driven by the loss of cell adhesion. To improve the survival of the transplanted MSCs, strategies to regulate apoptotic signaling and enhance cell adhesion have been developed, such as pretreatment with cytokines, growth factors, and antiapoptotic molecules, genetic modifications, and hypoxic preconditioning. More appropriate animal models and a greater understanding of the therapeutic mechanisms of MSCs will be required for their successful clinical application. Nevertheless, the development of stem cell therapies using MSCs has the potential to treat degenerative diseases. This review discusses various approaches to improving MSC survival by inhibiting anoikis.

scholarly journals Pharmacological Properties of Chalcones: A Review of Preclinical Including Molecular Mechanisms and Clinical Evidence

2021 ◽  
Vol 11 ◽  
Author(s):  
Bahare Salehi ◽  
Cristina Quispe ◽  
Imane Chamkhi ◽  
Nasreddine El Omari ◽  
Abdelaali Balahbib ◽  
...  
Keyword(s):  
Clinical Studies ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Clinical Signs ◽  
Signs And Symptoms ◽  
Clinical Signs And Symptoms ◽  
Skin Conditions ◽  
Underlying Mechanisms ◽  
Preclinical And Clinical Studies

Chalcones are among the leading bioactive flavonoids with a therapeutic potential implicated to an array of bioactivities investigated by a series of preclinical and clinical studies. In this article, different scientific databases were searched to retrieve studies depicting the biological activities of chalcones and their derivatives. This review comprehensively describes preclinical studies on chalcones and their derivatives describing their immense significance as antidiabetic, anticancer, anti-inflammatory, antimicrobial, antioxidant, antiparasitic, psychoactive, and neuroprotective agents. Besides, clinical trials revealed their use in the treatment of chronic venous insufficiency, skin conditions, and cancer. Bioavailability studies on chalcones and derivatives indicate possible hindrance and improvement in relation to its nutraceutical and pharmaceutical applications. Multifaceted and complex underlying mechanisms of chalcone actions demonstrated their ability to modulate a number of cancer cell lines, to inhibit a number of pathological microorganisms and parasites, and to control a number of signaling molecules and cascades related to disease modification. Clinical studies on chalcones revealed general absence of adverse effects besides reducing the clinical signs and symptoms with decent bioavailability. Further studies are needed to elucidate their structure activity, toxicity concerns, cellular basis of mode of action, and interactions with other molecules.

Hypoxic preconditioning enhances the therapeutic potential of the secretome from cultured human mesenchymal stem cells in experimental traumatic brain injury

2012 ◽  
Vol 124 (3) ◽  
pp. 165-176 ◽  
Author(s):  
Ching-Ping Chang ◽  
Chung-Ching Chio ◽  
Chong-Un Cheong ◽  
Chien-Ming Chao ◽  
Bor-Chieh Cheng ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Brain Injury ◽  
Growth Factor ◽  
Brain Damage ◽  
Rat Model ◽  
Therapeutic Potential ◽  
Hypoxic Preconditioning ◽  
Human Mscs

Bone-marrow-derived human MSCs (mesenchymal stem cells) support repair when administered to animals with TBI (traumatic brain injury) in large part through secreted trophic factors. We directly tested the ability of the culture medium (or secretome) collected from human MSCs under normoxic or hypoxic conditions to protect neurons in a rat model of TBI. Concentrated conditioned medium from cultured human MSCs or control medium was infused through the tail vein of rats subjected to TBI. We have demonstrated that MSCs cultured in hypoxia were superior to those cultured in normoxia in inducing expression of both HGF (hepatocyte growth factor) and VEGF (vascular endothelial growth factor) in the cultured medium. We showed further that rats treated with the secretome from both normoxic- and hypoxic-preconditioned MSCs performed significantly better than the controls in both motor and cognitive functional test. Subsequent post-mortem evaluation of brain damage at the 4-day time point confirmed that both normoxic- and hypoxic-preconditioned MSC secretome-treated rats had significantly greater numbers of newly forming neurons, but significantly less than the controls in brain damaged volume and apoptosis. The TBI rats treated with hypoxic-preconditioned MSC secretome performed significantly better in both motor and cognitive function tests and neurogenesis, and had significantly less brain damage than the TBI rats treated with the normoxic-preconditioned MSC secretome. Collectively, these findings suggest that MSCs secrete bioactive factors, including HGF and VEGF, that stimulate neurogenesis and improve outcomes of TBI in a rat model. Hypoxic preconditioning enhances the secretion of these bioactive factors from the MSCs and the therapeutic potential of the cultured MSC secretome in experimental TBI.

Buprenorphine: prospective novel therapy for depression and PTSD

2020 ◽  
Vol 50 (6) ◽  
pp. 881-893
Author(s):  
Caitlin A. Madison ◽  
Shoshana Eitan
Keyword(s):  
Clinical Studies ◽  
Therapeutic Potential ◽  
Kappa Opioid Receptor ◽  
Mental Illnesses ◽  
Bibliographic Databases ◽  
Medical Conditions ◽  
Endogenous Opioid ◽  
Beneficial Effects ◽  
Ability To Act ◽  
Preclinical And Clinical Studies

AbstractBackgroundDepression and post-traumatic stress disorder (PTSD) are leading causes of disability and loss of life by suicide. Currently, there are less than satisfactory medical solutions to treat these mental disorders. Here, we explore recent preclinical and clinical studies demonstrating the potential of using buprenorphine to treat major depressive disorder, treatment-resistant depression, and PTSD.MethodBibliographic databases were searched to include preclinical and clinical studies demonstrating the therapeutic potential of buprenorphine and the involvement of the kappa opioid receptor (KOR) in mediating these effects.ResultsOriginal clinical studies examining the effectiveness of buprenorphine to treat depression were mixed. The majority of participants in the PTSD studies were males and suffer from chronic pain and/or substance use disorders. Nonetheless, these recent studies and analyses established proof of concept warranting farther investigations. Additionally, KOR likely mediates the antidepressant and some of the anxiolytic effects of buprenorphine. Still, it appears that the full spectrum of buprenorphine's beneficial effects might be due to activity at other opioid receptors as well.ConclusionsPharmaceuticals' abilities to treat medical conditions directly relates to their ability to act upon the endogenous biological systems related to the conditions. Thus, these recent findings are likely a reflection of the central role that the endogenous opioid system has in these mental illnesses. Further studies are necessary to study the involvement of endogenous opioid systems, and specifically KOR, in mediating buprenorphine's beneficial effects and the ability to treat these medical conditions while minimizing risks for misuse and diversion.

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