scholarly journals Mesenchymal Stem Cell-Derived Exosomes as New Remedy for the Treatment of Neurocognitive Disorders

2021 ◽  
Vol 22 (3) ◽  
pp. 1433
Author(s):  
Carl Randall Harrell ◽  
Ana Volarevic ◽  
Valentin Djonov ◽  
Vladislav Volarevic
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Experimental Studies ◽  
Neurocognitive Disorders ◽  
Neural Cells ◽  
Cellular Mechanisms ◽  
Neural Growth ◽  
Neuro Inflammation

Mesenchymal stem cell (MSC)-derived exosomes (MSC-Exo) are nano-sized extracellular vesicles enriched with MSC-sourced neuroprotective and immunomodulatory microRNAs, neural growth factors, and anti-inflammatory cytokines, which attenuate neuro-inflammation, promote neo-vascularization, induce neurogenesis, and reduce apoptotic loss of neural cells. Accordingly, a large number of experimental studies demonstrated MSC-Exo-dependent improvement of cognitive impairment in experimental animals. In this review article, we summarized current knowledge about molecular and cellular mechanisms that were responsible for MSC-Exo-based restoration of cognitive function, emphasizing therapeutic potential of MSC-Exos in the treatment of neurocognitive disorders.

scholarly journals Molecular Mechanisms Responsible for Therapeutic Potential of Mesenchymal Stem Cell-Derived Secretome

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 467 ◽  
Author(s):  
Carl Harrell ◽  
Crissy Fellabaum ◽  
Nemanja Jovicic ◽  
Valentin Djonov ◽  
Nebojsa Arsenijevic ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Genetic Material ◽  
Cell Number ◽  
Target Cells ◽  
Therapeutic Effects ◽  
Cellular Mechanisms ◽  
Tissue Repair And Regeneration

Mesenchymal stem cell (MSC)-sourced secretome, defined as the set of MSC-derived bioactive factors (soluble proteins, nucleic acids, lipids and extracellular vesicles), showed therapeutic effects similar to those observed after transplantation of MSCs. MSC-derived secretome may bypass many side effects of MSC-based therapy, including unwanted differentiation of engrafted MSCs. In contrast to MSCs which had to be expanded in culture to reach optimal cell number for transplantation, MSC-sourced secretome is immediately available for treatment of acute conditions, including fulminant hepatitis, cerebral ischemia and myocardial infarction. Additionally, MSC-derived secretome could be massively produced from commercially available cell lines avoiding invasive cell collection procedure. In this review article we emphasized molecular and cellular mechanisms that were responsible for beneficial effects of MSC-derived secretomes in the treatment of degenerative and inflammatory diseases of hepatobiliary, respiratory, musculoskeletal, gastrointestinal, cardiovascular and nervous system. Results obtained in a large number of studies suggested that administration of MSC-derived secretomes represents a new, cell-free therapeutic approach for attenuation of inflammatory and degenerative diseases. Therapeutic effects of MSC-sourced secretomes relied on their capacity to deliver genetic material, growth and immunomodulatory factors to the target cells enabling activation of anti-apoptotic and pro-survival pathways that resulted in tissue repair and regeneration.

scholarly journals Mesenchymal Stem Cell-Derived Exosomes: Biological Function and Their Therapeutic Potential in Radiation Damage

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 42
Author(s):  
Xiaoyu Pu ◽  
Siyang Ma ◽  
Yan Gao ◽  
Tiankai Xu ◽  
Pengyu Chang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Radiation Damage ◽  
Therapeutic Potential ◽  
Damage Model ◽  
Bioactive Substances ◽  
Radiation Induced ◽  
Insight Into

Radiation-induced damage is a common occurrence in cancer patients who undergo radiotherapy. In this setting, radiation-induced damage can be refractory because the regeneration responses of injured tissues or organs are not well stimulated. Mesenchymal stem cells have become ideal candidates for managing radiation-induced damage. Moreover, accumulating evidence suggests that exosomes derived from mesenchymal stem cells have a similar effect on repairing tissue damage mainly because these exosomes carry various bioactive substances, such as miRNAs, proteins and lipids, which can affect immunomodulation, angiogenesis, and cell survival and proliferation. Although the mechanisms by which mesenchymal stem cell-derived exosomes repair radiation damage have not been fully elucidated, we intend to translate their biological features into a radiation damage model and aim to provide new insight into the management of radiation damage.

Mesenchymal Stem Cell Therapy for Acetaminophen-Related Liver Injury: A Systematic Review and Meta-Analysis of Experimental Studies in Vivo

2021 ◽  
Vol 16 ◽  
Author(s):  
Li Wang ◽  
Yiwen Zhang ◽  
Jiajun Zhong ◽  
Yuan Zhang ◽  
Shuisheng Zhou ◽  
...  
Keyword(s):  
Systematic Review ◽  
Stem Cell ◽  
Liver Injury ◽  
Mesenchymal Stem Cell ◽  
Small Sample Size ◽  
Meta Analysis ◽  
Experimental Studies ◽  
Small Sample ◽  
Control Group

Objective: The efficacy of mesenchymal stem cell (MSC) therapy in acetaminophen-induced liver injury has been investigated in animal experiments, but individual studies with a small sample size cannot be used to draw a clear conclusion. Therefore, we conducted a systematic review and meta-analysis of preclinical studies to explore the potential of using MSCs in acetaminophen-induced liver injury. Methods: Eight databases were searched for studies reporting the effects of MSCs on acetaminophen hepatoxicity. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were used. SYRCLE’s risk of bias tool for animal studies was applied to assess the methodological quality. A meta-analysis was performed by using RevMan 5.4 and STATA/SE 16.0 software. Results: Eleven studies involving 159 animals were included according to PRISMA statement guidelines. Significant associations were found for MSCs with the levels of alanine transaminase (ALT) (standardized mean difference (SMD) − 2.58, p < 0.0001), aspartate aminotransferase (AST) (SMD − 1.75, p = 0.001), glutathione (GSH) (SMD 3.7, p < 0.0001), superoxide dismutase (SOD) (SMD 1.86, p = 0.022), interleukin 10 (IL-10) (SMD 5.14, p = 0.0002) and tumor necrosis factor-α (TNF-α) (SMD − 4.48, p = 0.011) compared with those in the control group. The subgroup analysis showed that the tissue source of MSCs significantly affected the therapeutic efficacy (p < 0.05). Conclusion: Our meta-analysis results demonstrate that MSCs could be a potential treatment for acetaminophen-related liver injury.

scholarly journals Therapeutic Potential of Limbal Mesenchymal Stem Cell Secretome for Repair Ocular Surface in Experimental of Dry Eye Disease

2021 ◽  
Vol 83 (1) ◽  
Author(s):  
Ni Made Inten Lestari ◽  
Evelyn Komaratih ◽  
Fedik A. Rantam ◽  
Yuyun Rindiastuti ◽  
Cita Rosita Sigit Prakoeswa
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Dry Eye ◽  
Ocular Surface ◽  
Therapeutic Potential ◽  
Dry Eye Disease ◽  
Eye Disease

scholarly journals Physoxia alters human mesenchymal stem cell secretome

2021 ◽  
Vol 12 ◽  
pp. 204173142110561
Author(s):  
Marwan M Merkhan ◽  
Matthew T Shephard ◽  
Nicholas R Forsyth
Keyword(s):  
Stem Cell ◽  
Growth Factor ◽  
Mesenchymal Stem Cell ◽  
Therapeutic Potential ◽  
Interleukin 2 ◽  
Human Mesenchymal Stem Cell ◽  
Total Protein Content ◽  
Necrosis Factor Alpha ◽  
Oxygen Conditions ◽  
Endothelial Growth Factor

The human mesenchymal stem cell (hMSC) secretome has pleiotropic effects which underpin their therapeutic potential. hMSC serum-free conditioned media (SFCM) has been determined to contain a variety of cytokines with roles in regeneration and suppression of inflammation. Physiological oxygen (physoxia) has been demonstrated to impact upon a number of facets of hMSC biology and we hypothesized that the secretome would be similarly modified. We tested a range of oxygen conditions; 21% O2 (air oxygen (AO)), 2% O2 (intermittent hypoxia (IH)) and 2% O2 Workstation (physoxia (P)) to evaluate their effect on hMSC secretome profiles. Total protein content of secretome was upregulated in IH and P (>3 fold vs AO) and IH (>1 fold vs P). Focused cytokine profiling indicated global upregulation in IH of all 31 biomolecules tested in comparison to AO and P with basic-nerve growth factor (bNGF) and granulocyte colony-stimulating factor (GCSF) (>3 fold vs AO) and bNGF and Rantes (>3 fold vs P) of note. Similarly, upregulation of interferon gamma-induced protein 10 (IP10) was noted in P (>3 fold vs AO). Interleukin-2 (IL2) and Rantes (in AO and P) and adiponectin, IL17a, and epidermal growth factor (EGF) (in AO only) were entirely absent or below detection limits. Quantitative analysis validated the pattern of IH-induced upregulation in vascular endothelial growth factor (VEGF), placental growth factor-1 (PIGF1), Tumor necrosis factor alpha (TNFa), IL2, IL4, and IL10 when compared to AO and P. In summary, modulation of environmental oxygen alters both secretome concentration and composition. This consideration will likely impact on delivering improved mechanistic understanding and potency effects of hMSC-based therapeutics.

Molecular and Cellular Mechanisms Involved in Mesenchymal Stem Cell-Based Therapy of Inflammatory Bowel Diseases

2017 ◽  
Vol 14 (2) ◽  
pp. 153-165 ◽  
Author(s):  
Bojana Simovic Markovic ◽  
Tatjana Kanjevac ◽  
C. Randall Harrell ◽  
Marina Gazdic ◽  
Crissy Fellabaum ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Inflammatory Bowel Diseases ◽  
Cellular Mechanisms ◽  
Cell Based Therapy ◽  
Bowel Diseases ◽  
Inflammatory Bowel

scholarly journals Targeted Delivery of Mesenchymal Stem Cell-Derived Nanovesicles for Spinal Cord Injury Treatment

2020 ◽  
Vol 21 (11) ◽  
pp. 4185
Author(s):  
Ju-Ro Lee ◽  
Jae Won Kyung ◽  
Hemant Kumar ◽  
Sung Pil Kwon ◽  
Seuk Young Song ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Clinical Application ◽  
Targeted Delivery ◽  
Therapeutic Potential ◽  
Systemic Injection ◽  
Cord Injury ◽  
Macrophage Membrane

Due to the safety issues and poor engraftment of mesenchymal stem cell (MSC) implantation, MSC-derived exosomes have been spotlighted as an alternative therapy for spinal cord injury (SCI). However, insufficient productivity of exosomes limits their therapeutic potential for clinical application. Moreover, low targeting ability of unmodified exosomes is a critical obstacle for their further applications as a therapeutic agent. In the present study, we fabricated macrophage membrane-fused exosome-mimetic nanovesicles (MF-NVs) from macrophage membrane-fused umbilical cord blood-derived MSCs (MF-MSCs) and confirmed their therapeutic potential in a clinically relevant mouse SCI model (controlled mechanical compression injury model). MF-NVs contained larger quantity of ischemic region-targeting molecules compared to normal MSC-derived nanovesicles (N-NVs). The targeting molecules in MF-NVs, which were derived from macrophage membranes, increased the accumulation of MF-NVs in the injured spinal cord after the in vivo systemic injection. Increased accumulation of MF-NVs attenuated apoptosis and inflammation, prevented axonal loss, enhanced blood vessel formation, decreased fibrosis, and consequently, improved spinal cord function. Synthetically, we developed targeting efficiency-potentiated exosome-mimetic nanovesicles and present their possibility of clinical application for SCI.

The Therapeutic Potential of Mesenchymal Stem Cell–Derived Exosomes in Treatment of Neurodegenerative Diseases

2019 ◽  
Vol 56 (12) ◽  
pp. 8157-8167 ◽  
Author(s):  
Armita Mahdavi Gorabi ◽  
Nasim Kiaie ◽  
George E. Barreto ◽  
Morgayn I. Read ◽  
Hossein Ahmadi Tafti ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Neurodegenerative Diseases ◽  
Therapeutic Potential
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