scholarly journals Pulmonary Mesenchymal Stem Cells in Mild Cases of COVID-19 Are Dedicated to Proliferation; In Severe Cases, They Control Inflammation, Make Cell Dispersion, and Tissue Regeneration

2022 ◽  
Vol 12 ◽  
Author(s):  
Andrea Henriques-Pons ◽  
Daniela Gois Beghini ◽  
Vanessa dos Santos Silva ◽  
Samuel Iwao Horita ◽  
Fabrício Alves Barbosa da Silva
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tissue Regeneration ◽  
Adult Stem Cells ◽  
Target Genes ◽  
Therapeutic Potential ◽  
Control Cell ◽  
Cell Based Therapy ◽  
Cell Dispersion ◽  
Upregulated Genes

Mesenchymal stem cells (MSCs) are multipotent adult stem cells present in virtually all tissues; they have potent self-renewal capacity and differentiate into multiple cell types. For many reasons, these cells are a promising therapeutic alternative to treat patients with severe COVID-19 and pulmonary post-COVID sequelae. These cells are not only essential for tissue regeneration; they can also alter the pulmonary environment through the paracrine secretion of several mediators. They can control or promote inflammation, induce other stem cells differentiation, restrain the virus load, and much more. In this work, we performed single-cell RNA-seq data analysis of MSCs in bronchoalveolar lavage samples from control individuals and COVID-19 patients with mild and severe clinical conditions. When we compared samples from mild cases with control individuals, most genes transcriptionally upregulated in COVID-19 were involved in cell proliferation. However, a new set of genes with distinct biological functions was upregulated when we compared severely affected with mild COVID-19 patients. In this analysis, the cells upregulated genes related to cell dispersion/migration and induced the γ-activated sequence (GAS) genes, probably triggered by IFNGR1 and IFNGR2. Then, IRF-1 was upregulated, one of the GAS target genes, leading to the interferon-stimulated response (ISR) and the overexpression of many signature target genes. The MSCs also upregulated genes involved in the mesenchymal-epithelial transition, virus control, cell chemotaxis, and used the cytoplasmic RNA danger sensors RIG-1, MDA5, and PKR. In a non-comparative analysis, we observed that MSCs from severe cases do not express many NF-κB upstream receptors, such as Toll-like (TLRs) TLR-3, -7, and -8; tumor necrosis factor (TNFR1 or TNFR2), RANK, CD40, and IL-1R1. Indeed, many NF-κB inhibitors were upregulated, including PPP2CB, OPTN, NFKBIA, and FHL2, suggesting that MSCs do not play a role in the “cytokine storm” observed. Therefore, lung MSCs in COVID-19 sense immune danger and act protectively in concert with the pulmonary environment, confirming their therapeutic potential in cell-based therapy for COVID-19. The transcription of MSCs senescence markers is discussed.

Therapeutic Potential of Amniotic Fluid Derived Mesenchymal Stem Cells Based on their Differentiation Capacity and Immunomodulatory Properties

2019 ◽  
Vol 14 (4) ◽  
pp. 327-336 ◽  
Author(s):  
Carl R. Harrell ◽  
Marina Gazdic ◽  
Crissy Fellabaum ◽  
Nemanja Jovicic ◽  
Valentin Djonov ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Animal Models ◽  
Amniotic Fluid ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Therapeutic Effects ◽  
Differentiation Potential ◽  
Differentiation Capacity ◽  
Cell Based Therapy

Background: Amniotic Fluid Derived Mesenchymal Stem Cells (AF-MSCs) are adult, fibroblast- like, self-renewable, multipotent stem cells. During the last decade, the therapeutic potential of AF-MSCs, based on their huge differentiation capacity and immunomodulatory characteristics, has been extensively explored in animal models of degenerative and inflammatory diseases. Objective: In order to describe molecular mechanisms responsible for the therapeutic effects of AFMSCs, we summarized current knowledge about phenotype, differentiation potential and immunosuppressive properties of AF-MSCs. Methods: An extensive literature review was carried out in March 2018 across several databases (MEDLINE, EMBASE, Google Scholar), from 1990 to present. Keywords used in the selection were: “amniotic fluid derived mesenchymal stem cells”, “cell-therapy”, “degenerative diseases”, “inflammatory diseases”, “regeneration”, “immunosuppression”. Studies that emphasized molecular and cellular mechanisms responsible for AF-MSC-based therapy were analyzed in this review. Results: AF-MSCs have huge differentiation and immunosuppressive potential. AF-MSCs are capable of generating cells of mesodermal origin (chondrocytes, osteocytes and adipocytes), neural cells, hepatocytes, alveolar epithelial cells, insulin-producing cells, cardiomyocytes and germ cells. AF-MSCs, in juxtacrine or paracrine manner, regulate proliferation, activation and effector function of immune cells. Due to their huge differentiation capacity and immunosuppressive characteristic, transplantation of AFMSCs showed beneficent effects in animal models of degenerative and inflammatory diseases of nervous, respiratory, urogenital, cardiovascular and gastrointestinal system. Conclusion: Considering the fact that amniotic fluid is obtained through routine prenatal diagnosis, with minimal invasive procedure and without ethical concerns, AF-MSCs represents a valuable source for cell-based therapy of organ-specific or systemic degenerative and inflammatory diseases.

scholarly journals Cell-Based Therapy for Stroke

Stroke ◽  
2020 ◽  
Vol 51 (9) ◽  
pp. 2854-2862 ◽  
Author(s):  
You Jeong Park ◽  
Kuniyasu Niizuma ◽  
Maxim Mokin ◽  
Mari Dezawa ◽  
Cesar V. Borlongan
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Ischemic Stroke ◽  
Cell Therapy ◽  
Therapeutic Potential ◽  
Host Tissue ◽  
In Vivo Models ◽  
Cell Based Therapy ◽  
Muse Cells

Stem cell-based regenerative therapies may rescue the central nervous system following ischemic stroke. Mesenchymal stem cells exhibit promising regenerative capacity in in vitro studies but display little to no incorporation in host tissue after transplantation in in vivo models of stroke. Despite these limitations, clinical trials using mesenchymal stem cells have produced some functional benefits ascribed to their ability to modulate the host’s inflammatory response coupled with their robust safety profile. Regeneration of ischemic brain tissue using stem cells, however, remains elusive in humans. Multilineage-differentiating stress-enduring (Muse) cells are a distinct subset of mesenchymal stem cells found sporadically in connective tissue of nearly every organ. Since their discovery in 2010, these endogenous reparative stem cells have been investigated for their therapeutic potential against a variety of diseases, including acute myocardial infarction, stroke, chronic kidney disease, and liver disease. Preclinical studies have exemplified Muse cells’ unique ability mobilize, differentiate, and engraft into damaged host tissue. Intravenously transplanted Muse cells in mouse lacunar stroke models afforded functional recovery and long-term engraftment into the host neural network. This mini-review article highlights these biological properties that make Muse cells an exceptional candidate donor source for cell therapy in ischemic stroke. Elucidating the mechanism behind the therapeutic potential of Muse cells will undoubtedly help optimize stem cell therapy for stroke and advance the field of regenerative medicine.

Abstract P506: Sirt6 Overexpression Inhibits Senescence And Inflammation In Human Mesenchymal Stem Cells

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Rahul Neupane ◽  
Darukeshwara Joladarashi ◽  
Keith Youker ◽  
Muthu Kumar Krishnamoorthi ◽  
Arvind Bhimaraj ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
High Glucose ◽  
Therapeutic Potential ◽  
Diabetic Patients ◽  
Human Mscs ◽  
Cell Based Therapy ◽  
Functional Efficiency ◽  
Genomics And Proteomics

Background: Mesenchymal Stem Cells (MSCs) offer regenerative and therapeutic potential in an injured tissue in diabetic conditions. But the functional efficiency of MSCs has been shown to decrease with diabetes and aging. This reduces the potential of cell-based therapy in diabetic patients. Recent studies have established the role of sirtuin family proteins in metabolic disease, inflammation, longevity, and DNA repair. However, their potential to be used as a therapeutic target in cardiomyopathy and heart failure remain unexplored. Objective: To investigate the role of Sirtuin 6 (SIRT6) in mesenchymal stem cells senescence and cardiac regeneration. Methods and Results: We performed genomics and proteomics in the human control and diabetic heart tissues collected from the heart transplant. Human MSCs were treated with high glucose and mouse MSCs were derived from the bone marrow of diabetic db/db mice for this study. We found that SIRT6 expression is reduced in the myocardium of diabetic patients compared to non-diabetic controls. The SIRT6 expression decreased in high glucose-treated human MSCs compared to mannitol-treated control MSCs as well as in db/db mice MSCs compared to control mice MSCs. These high glucose-treated human MSCs and db/db mice MSCs showed increased expression of senescence and inflammation-related markers like that in diabetic human myocardium. Furthermore, we used small interfering RNA (SIRT6-siRNA) in human MSCs to knock down the SIRT6 gene and validated our findings. Indeed, the knockdown of SIRT6 promoted senescence and inflammation in those MSCs. Finally, we used adeno-associated viruses (AAV-SIRT6) to overexpress SIRT6 in MSCs treated with high glucose and performed proteomic analysis. SIRT6 overexpression in high glucose-treated MSCs reduced the expression of senescence and inflammation related genes and proteins. Conclusion: Our results highlight the importance of SIRT6 in diabetic myocardium and its role in balancing senescence and inflammation in MSCs. The validation of such in vitro studies in a diabetic mouse model ( db/db ) along with transplantation of SIRT6 overexpressed db/db MSCs into the myocardium of diabetic mice could open doors to successfully use MSC therapy in diabetic patients in the future.

scholarly journals Perinatal sources of mesenchymal stem cells: Wharton’s jelly, amnion and chorion

2011 ◽  
Vol 16 (3) ◽  
Author(s):  
Malgorzata Witkowska-Zimny ◽  
Edyta Wrobel
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Biology ◽  
Adult Stem Cells ◽  
Therapeutic Potential ◽  
Autologous Transplantation ◽  
Embryonic Stem ◽  
Wharton’S Jelly ◽  
Wharton's Jelly

AbstractRecently, stem cell biology has become an interesting topic, especially in the context of treating diseases and injuries using transplantation therapy. Several varieties of human stem cells have been isolated and identified in vivo and in vitro. Ideally, stem cells for regenerative medical application should be found in abundant quantities, harvestable in a minimally invasive procedure, then safely and effectively transplanted to either an autologous or allogenic host. The two main groups of stem cells, embryonic stem cells and adult stem cells, have been expanded to include perinatal stem cells. Mesenchymal stem cells from perinatal tissue may be particularly useful in the clinic for autologous transplantation for fetuses and newborns, and after banking in later stages of life, as well as for in utero transplantation in case of genetic disorders.This review highlights the characteristics and therapeutic potential of three human mesenchymal stem cell types obtained from perinatal sources: Wharton’s jelly, the amnion, and the chorion.

scholarly journals Mesenchymal Stem Cell-Derived Extracellular Vesicles in Tissue Regeneration

2020 ◽  
Vol 29 ◽  
pp. 096368972090850 ◽  
Author(s):  
Bocheng Zhang ◽  
Xiaoyuan Tian ◽  
Jun Hao ◽  
Gang Xu ◽  
Weiguo Zhang
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Tissue Regeneration ◽  
Tissue Repair ◽  
Membrane Structure ◽  
Therapeutic Potential ◽  
Biological Functions ◽  
Self Renewal ◽  
Multipotent Stem Cells

Mesenchymal stem cells (MSCs) are multipotent stem cells that have attracted increasing interest in the field of regenerative medicine. Previously, the differentiation ability of MSCs was believed to be primarily responsible for tissue repair. Recent studies have shown that paracrine mechanisms play an important role in this process. MSCs can secrete soluble molecules and extracellular vesicles (EVs), which mediate paracrine communication. EVs contain large amounts of proteins and nucleic acids, such as mRNAs and microRNAs (miRNAs), and can transfer the cargo between cells. The cargoes are similar to those in MSCs and are not susceptible to degradation due to the protection of the EV bimolecular membrane structure. MSC-EVs can mimic the biological characteristics of MSCs, such as differentiation, maturation, and self-renewal. Due to their broad biological functions and their ability to transfer molecules between cells, EVs have been intensively studied by an increasing number of researchers with a focus on therapeutic applications, especially those of EVs secreted by MSCs. In this review, we discuss MSC-derived EVs and their therapeutic potential in tissue regeneration.

scholarly journals The therapeutic potential of mesenchymal stem cells in treating osteoporosis

2021 ◽  
Vol 54 (1) ◽  
Author(s):  
Tianning Chen ◽  
Tieyi Yang ◽  
Weiwei Zhang ◽  
Jin Shao
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Therapeutic Potential ◽  
Bone Fragility ◽  
Clinical Treatment ◽  
Post Transplantation ◽  
Cell Based Therapy ◽  
Metabolic Bone ◽  
Orthopedic Diseases

AbstractOsteoporosis (OP), a common systemic metabolic bone disease, is characterized by low bone mass, increasing bone fragility and a high risk of fracture. At present, the clinical treatment of OP mainly involves anti-bone resorption drugs and anabolic agents for bone, but their long-term use can cause serious side effects. The development of stem cell therapy and regenerative medicine has provided a new approach to the clinical treatment of various diseases, even with a hope for cure. Recently, the therapeutic advantages of the therapy have been shown for a variety of orthopedic diseases. However, these stem cell-based researches are currently limited to animal models; the uncertainty regarding the post-transplantation fate of stem cells and their safety in recipients has largely restricted the development of human clinical trials. Nevertheless, the feasibility of mesenchymal stem cells to treat osteoporotic mice has drawn a growing amount of intriguing attention from clinicians to its potential of applying the stem cell-based therapy as a new therapeutic approach to OP in the future clinic. In the current review, therefore, we explored the potential use of mesenchymal stem cells in human OP treatment.

scholarly journals New therapeutic approaches of mesenchymal stem cells-derived exosomes

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Jana Janockova ◽  
Lucia Slovinska ◽  
Denisa Harvanova ◽  
Timea Spakova ◽  
Jan Rosocha
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Experimental Models ◽  
Target Cells ◽  
Therapeutic Approaches ◽  
Paracrine Factors ◽  
New Therapeutic Approaches ◽  
Cell Based Therapy

AbstractMesenchymal stem cells (MSCs) have been demonstrated to have a great potential in the treatment of several diseases due to their differentiation and immunomodulatory capabilities and their ability to be easily cultured and manipulated. Recent investigations revealed that their therapeutic effect is largely mediated by the secretion of paracrine factors including exosomes. Exosomes reflect biophysical features of MSCs and are considered more effective than MSCs themselves. Alternative approaches based on MSC-derived exosomes can offer appreciable promise in overcoming the limitations and practical challenges observed in cell-based therapy. Furthermore, MSC-derived exosomes may provide a potent therapeutic strategy for various diseases and are promising candidates for cell-based and cell-free regenerative medicine. This review briefly summarizes the development of MSCs as a treatment for human diseases as well as describes our current knowledge about exosomes: their biogenesis and molecular composition, and how they exert their effects on target cells. Particularly, the therapeutic potential of MSC-derived exosomes in experimental models and recent clinical trials to evaluate their safety and efficacy are summarized in this study. Overall, this paper provides a current overview of exosomes as a new cell-free therapeutic agent.

scholarly journals Therapeutic Potential of Mesenchymal Stem Cells and Their Secretome in the Treatment of Glaucoma

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
C. Randall Harrell ◽  
Crissy Fellabaum ◽  
Aleksandar Arsenijevic ◽  
Bojana Simovic Markovic ◽  
Valentin Djonov ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Visual Information ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Therapeutic Agents ◽  
Dependent Manner ◽  
Cellular Mechanisms ◽  
Cell Based Therapy ◽  
Glaucoma Treatment

Glaucoma represents a group of progressive optic neuropathies characterized by gradual loss of retinal ganglion cells (RGCs), the neurons that conduct visual information from the retina to the brain. Elevated intraocular pressure (IOP) is considered the main reason for enhanced apoptosis of RGCs in glaucoma. Currently used therapeutic agents are not able to repopulate and/or regenerate injured RGCs and, therefore, are ineffective in most patients with advanced glaucoma. Accordingly, several new therapeutic approaches, including stem cell-based therapy, have been explored for the glaucoma treatment. In this review article, we emphasized current knowledge regarding molecular and cellular mechanisms responsible for beneficial effects of mesenchymal stem cells (MSCs) and their secretome in the treatment of glaucoma. MSCs produce neurotrophins and in an exosome-dependent manner supply injured RGCs with growth factors enhancing their survival and regeneration. Additionally, MSCs are able to generate functional RGC-like cells and induce proliferation of retinal stem cells. By supporting integrity of trabecular meshwork, transplanted MSCs alleviate IOP resulting in reduced loss of RGCs. Moreover, MSCs are able to attenuate T cell-driven retinal inflammation providing protection to the injured retinal tissue. In summing up, due to their capacity for neuroprotection and immunomodulation, MSCs and their secretome could be explored in upcoming clinical studies as new therapeutic agents for glaucoma treatment.

scholarly journals Therapeutic potential of non-adherent BM-derived mesenchymal stem cells in tissue regeneration

2008 ◽  
Vol 43 (1) ◽  
pp. 69-81 ◽  
Author(s):  
Z L Zhang ◽  
J Tong ◽  
R N Lu ◽  
A M Scutt ◽  
D Goltzman ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tissue Regeneration ◽  
Therapeutic Potential

scholarly journals TUDCA-Treated Mesenchymal Stem Cells Protect against ER Stress in the Hippocampus of a Murine Chronic Kidney Disease Model

2019 ◽  
Vol 20 (3) ◽  
pp. 613 ◽  
Author(s):  
Jun Lee ◽  
Yeo Yoon ◽  
Sang Lee
Keyword(s):  
Chronic Kidney Disease ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Kidney Disease ◽  
Er Stress ◽  
Therapeutic Potential ◽  
Cellular Prion Protein ◽  
Ros Generation ◽  
Uremic Toxin ◽  
Cell Based Therapy

Chronic kidney disease (CKD) leads to the loss of kidney function, as well as the dysfunction of several other organs due to the release of uremic toxins into the system. In a murine CKD model, reactive oxygen species (ROS) generation and endoplasmic reticulum (ER) stress are increased in the hippocampus. Mesenchymal stem cells (MSCs) are one of the candidates for cell-based therapy for CKD; however severe pathophysiological conditions can decrease their therapeutic potential. To address these issues, we established tauroursodeoxycholic acid (TUDCA)-treated MSCs using MSCs isolated from patients with CKD (CKD-hMSCs) and assessed the survival and ROS generation of neural cell line SH-SY5Y cells by co-culturing with TUDCA-treated CKD-hMSCs. In the presence of the uremic toxin P-cresol, the death of SH-SY5Y cells was induced by ROS-mediated ER stress. Co-culture with TUDCA-treated CKD-hMSCs increased anti-oxidant enzyme activities in SH-SY5Y cells through the upregulation of the cellular prion protein (PrPC) expression. Upregulated PrPC expression in SH-SY5Y cells protected against CKD-mediated ER stress and apoptosis. In an adenine-induced murine CKD model, injection with TUDCA-treated CKD-hMSCs suppressed ROS generation and ER stress in the hippocampus. These results indicate that TUDCA-treated CKD-hMSCs prevent the CKD-mediated cell death of SH-SY5Y cells by inhibiting ER stress. Our study suggests that treatment with TUDCA could be a powerful strategy for developing autologous MSC-based therapeutics for patients with CKD, and that PrPC might be a pivotal target for protecting neural cells from CKD-mediated ER stress.

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