scholarly journals Challenges and advances in clinical applications of mesenchymal stromal cells

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Tian Zhou ◽  
Zenan Yuan ◽  
Jianyu Weng ◽  
Duanqing Pei ◽  
Xin Du ◽  
...  

AbstractMesenchymal stromal cells (MSCs), also known as mesenchymal stem cells, have been intensely investigated for clinical applications within the last decades. However, the majority of registered clinical trials applying MSC therapy for diverse human diseases have fallen short of expectations, despite the encouraging pre-clinical outcomes in varied animal disease models. This can be attributable to inconsistent criteria for MSCs identity across studies and their inherited heterogeneity. Nowadays, with the emergence of advanced biological techniques and substantial improvements in bio-engineered materials, strategies have been developed to overcome clinical challenges in MSC application. Here in this review, we will discuss the major challenges of MSC therapies in clinical application, the factors impacting the diversity of MSCs, the potential approaches that modify MSC products with the highest therapeutic potential, and finally the usage of MSCs for COVID-19 pandemic disease.

2019 ◽  
Vol 1 (1) ◽  
pp. 36-39
Author(s):  
Bernd Giebel ◽  
Verena Börger ◽  
Mario Gimona ◽  
Eva Rohde

Human mesenchymal stem/stromal cells (MSCs) represent a promising tool in regenerative medicine. Until now, almost one thousand NIH-registered clinical trials investigated their immunomodulatory and pro-regenerative therapeutic potential in various diseases. Despite controversial reports regarding the efficacy of MSC-treatments, MSCs appear to exert their beneficial effects in a paracrine manner rather than by cell replacement. In this context, extracellular vesicles (EVs), such as exosomes and microvesicles, seem to induce the MSCs’ therapeutic effects. Here, we briefly illustrate the potential of MSC-EVs as therapeutic agent of the future.


2020 ◽  
Vol 16 (1) ◽  
Author(s):  
Sonja Prpar Mihevc ◽  
Vesna Kokondoska Grgich ◽  
Andreja Nataša Kopitar ◽  
Luka Mohorič ◽  
Gregor Majdič

ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142110050
Author(s):  
Susann Hetze ◽  
Ulrich Sure ◽  
Manfred Schedlowski ◽  
Martin Hadamitzky ◽  
Lennart Barthel

Animal models are still indispensable for understanding the basic principles of glioma development and invasion. Preclinical approaches aim to analyze the treatment efficacy of new drugs before translation into clinical trials is possible. Various animal disease models are available, but not every approach is useful for addressing specific questions. In recent years, it has become increasingly evident that the tumor microenvironment plays a key role in the nature of glioma. In addition to providing an overview, this review evaluates available rodent models in terms of usability for research on the glioma microenvironment.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Dhavan Sharma ◽  
Feng Zhao

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected nearly 118 million people and caused ~2.6 million deaths worldwide by early 2021, during the coronavirus disease 2019 (COVID-19) pandemic. Although the majority of infected patients show mild-to-moderate symptoms, a small fraction of patients develops severe symptoms. Uncontrolled cytokine production and the lack of substantive adaptive immune response result in hypoxia, acute respiratory distress syndrome (ARDS), or multiple organ failure in severe COVID-19 patients. Since the current standard of care treatment is insufficient to alleviate severe COVID-19 symptoms, many clinics have been prompted to perform clinical trials involving the infusion of mesenchymal stem cells (MSCs) due to their immunomodulatory and therapeutic properties. Several phases I/II clinical trials involving the infusion of allogenic MSCs have been performed last year. The focus of this review is to critically evaluate the safety and efficacy outcomes of the most recent, placebo-controlled phase I/II clinical studies that enrolled a larger number of patients, in order to provide a statistically relevant and comprehensive understanding of MSC’s therapeutic potential in severe COVID-19 patients. Clinical outcomes obtained from these studies clearly indicate that: (i) allogenic MSC infusion in COVID-19 patients with ARDS is safe and effective enough to decreases a set of inflammatory cytokines that may drive COVID-19 associated cytokine storm, and (ii) MSC infusion efficiently improves COVID-19 patient survival and reduces recovery time. These findings strongly support further investigation into MSC-infusion in larger clinical trials for COVID-19 patients with ARDS, who currently have a nearly 50% of mortality rate.


Author(s):  
Ahmet Cevik Tufan

Abstract:: The cause of coronavirus disease 2019 (COVID-19) known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, formerly designated 2019-nCoV) was first discovered in December 2019 in Wuhan, China. It then spread rapidly worldwide. Investigation for discovery of drugs to cure this disease continues. The currently accepted treatments are supportive but there is no specific disease curing intervention found yet. Since mid-February, therapies involving mesenchymal stem/stromal cells (MSCs) have been proposed for the treatment of patients with COVID-19. In light of these recent developments this review will focus on: i) the mechanism of SARS-CoV-2 action and the subsequent pathology in COVID-19, ii) the proposed mechanism(s) of outcome-improving action of MSCs or MSC-derived extracellular vesicles in COVID-19 pneumonia, iii) registered MSC-based clinical trials and interventions for the treatment of COVID-19, iv) published case studies/series/trials reporting the use of MSC-based treatments in COVID-19 cases, and finally v) the need for authority regulations and clinical guidelines for MSC-based treatment strategies for COVID-19.


2019 ◽  
Vol 20 (18) ◽  
pp. 4597 ◽  
Author(s):  
Sharon Eleuteri ◽  
Alessandra Fierabracci

Mesenchymal stem cells (MSCs) have regenerative, immunoregulatory properties and can be easily isolated and expanded in vitro. Despite being a powerful tool for clinical applications, they present limitations in terms of delivery, safety, and variability of therapeutic response. Interestingly, the MSC secretome composed by cytokines, chemokines, growth factors, proteins, and extracellular vesicles, could represent a valid alternative to their use. It is noteworthy that MSC-derived extracellular vesicles (MSC-EVs) have the same effect and could be advantageous compared to the parental cells because of their specific miRNAs load. MiRNAs could be useful both in diagnostic procedures such as “liquid biopsy” to identify early pathologies and in the therapeutic field. Not only are MSC-EVs’ preservation, transfer, and production easier, but their administration is also safer, hence some clinical trials are ongoing. However, much effort is required to improve the characterization of EVs to avoid artifacts and guarantee reproducibility of the studies.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Eriko G. Suto ◽  
Yo Mabuchi ◽  
Saki Toyota ◽  
Miyu Taguchi ◽  
Yuna Naraoka ◽  
...  

Abstract Somatic stem cells have been isolated from multiple human tissues for their potential usefulness in cell therapy. Currently, mesenchymal stromal cells (MSCs) are prepared after several passages requiring a few months of cell culture. In this study, we used a prospective isolation method of somatic stem cells from gestational or fat tissues, which were identified using CD73 antibody. CD73-positive population from various tissues existed individually in flowcytometric pattern, especially subcutaneous fat- and amniotic-derived cells showed the highest enrichment of CD73-positive cells. Moreover, the cell populations isolated with the prospective method showed higher proliferative capacity and stem cell marker expression, compared to the cell populations which isolated through several passages of culturing whole living cells: which we named “conventional method” in this paper. Furthermore, the therapeutic potential of CD73-positive cells was evaluated in vivo using a mouse model of pulmonary fibrosis. After intranasal administration, murine CD73-positive cells reduced macrophage infiltration and inhibited fibrosis development. These results suggest that further testing using CD73-positive cells may be beneficial to help establish the place in regenerative medicine use.


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