scholarly journals Modulation of Mesenchymal Stem Cells for Enhanced Therapeutic Utility in Ischemic Vascular Diseases

2021 ◽  
Vol 23 (1) ◽  
pp. 249
Author(s):  
Sally L. Elshaer ◽  
Salma H. Bahram ◽  
Pranav Rajashekar ◽  
Rajashekhar Gangaraju ◽  
Azza B. El-Remessy
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Vascular Diseases ◽  
Bioactive Molecules ◽  
Trophic Factors ◽  
Complex Nature ◽  
Post Transplantation ◽  
Multipotent Stem Cells ◽  
Paracrine Effects ◽  
Functional Capabilities

Mesenchymal stem cells are multipotent stem cells isolated from various tissue sources, including but not limited to bone marrow, adipose, umbilical cord, and Wharton Jelly. Although cell-mediated mechanisms have been reported, the therapeutic effect of MSCs is now recognized to be primarily mediated via paracrine effects through the secretion of bioactive molecules, known as the “secretome”. The regenerative benefit of the secretome has been attributed to trophic factors and cytokines that play neuroprotective, anti-angiogenic/pro-angiogenic, anti-inflammatory, and immune-modulatory roles. The advancement of autologous MSCs therapy can be hindered when introduced back into a hostile/disease environment. Barriers include impaired endogenous MSCs function, limited post-transplantation cell viability, and altered immune-modulatory efficiency. Although secretome-based therapeutics have gained popularity, many translational hurdles, including the heterogeneity of MSCs, limited proliferation potential, and the complex nature of the secretome, have impeded the progress. This review will discuss the experimental and clinical impact of restoring the functional capabilities of MSCs prior to transplantation and the progress in secretome therapies involving extracellular vesicles. Modulation and utilization of MSCs–secretome are most likely to serve as an effective strategy for promoting their ultimate success as therapeutic modulators.

scholarly journals Application of Mesenchymal Stem Cells in Inflammatory and Fibrotic Diseases

2020 ◽  
Vol 21 (21) ◽  
pp. 8366
Author(s):  
Jae-Sung Ryu ◽  
Eun-Jeong Jeong ◽  
Jong-Yeup Kim ◽  
Soon Ju Park ◽  
Won Seok Ju ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Trophic Factors ◽  
Therapeutic Effects ◽  
Multipotent Stem Cells ◽  
Therapeutic Properties ◽  
Fibrotic Diseases ◽  
Plastic Surfaces

Mesenchymal stem cells (MSCs) are multipotent stem cells that can be isolated from various tissues in the adult body. MSCs should be characterized by three criteria for regenerative medicine. MSCs must (1) adhere to plastic surfaces, (2) express specific surface antigens, and (3) differentiate into mesodermal lineages, including chondrocytes, osteoblasts, and adipocytes, in vitro. Interestingly, MSCs have immunomodulatory features and secrete trophic factors and immune receptors that regulate the microenvironment in host tissue. These specific and unique therapeutic properties make MSCs ideal as therapeutic agents in vivo. Specifically, pre-clinical and clinical investigators generated inflammatory and fibrotic diseases models, and then transplantation of MSCs into diseases models for therapeutic effects investigation. In this review, we characterize MSCs from various tissues and describe their applications for treating various inflammation and fibrotic diseases.

scholarly journals Trophic Activity and Phenotype of Adipose Tissue-Derived Mesenchymal Stem Cells as a Background of Their Regenerative Potential

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Beata Kocan ◽  
Aleksandra Maziarz ◽  
Jacek Tabarkiewicz ◽  
Takahiro Ochiya ◽  
Agnieszka Banaś-Ząbczyk
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Cell Types ◽  
Trophic Factors ◽  
Phenotypic Characterization ◽  
Paracrine Effects ◽  
Trophic Activity ◽  
Cell Proliferation And Differentiation ◽  
And Migration

There has been an increased interest in mesenchymal stem cells from adipose tissue, due to their abundance and accessibility with no ethical concerns. Their multipotent properties make them appropriate for regenerative clinical applications. It has been shown that adipose-derived stem cells (ASCs) may differ between the origin sites. Moreover, a variety of internal and external factors may affect their biological characteristics, as what we aimed to highlight in this review. It has been demonstrated that ASCs secrete multiple trophic factors that are capable of stimulating cell proliferation and differentiation and migration of various cell types. Particular attention should be given to exosomes, since it is known that they contribute to the paracrine effects of MSCs. Secretion of trophic agents by ASCs is thought to be in a greater importance for regenerative medicine applications, rather than cells engraftment to the site of injury and their differentiation ability. The surface marker profile of ASCs seems to be similar to that of the mesenchymal stem cells from bone marrow, although some molecular differences are observed. Thus, in this review, we have attempted to define trophic activity, as well as phenotypic characterization of ASCs, as crucial factors for therapeutic usage.

scholarly journals Mesenchymal Stem Cell-Based Immunomodulation: Properties and Clinical Application

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Mengyuan Wang ◽  
Quan Yuan ◽  
Liang Xie
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Bioactive Molecules ◽  
Therapeutic Application ◽  
Multipotent Stem Cells ◽  
Paracrine Effects ◽  
Tissue Repair And Regeneration ◽  
Physiological Processes ◽  
Research Findings ◽  
Adaptive Immune Systems

Mesenchymal stem cells (MSCs) are multipotent stem cells characterized by self-renewal, production of clonal cell populations, and multilineage differentiation. They exist in nearly all tissues and play a significant role in tissue repair and regeneration. Additionally, MSCs possess wide immunoregulatory properties via interaction with immune cells in both innate and adaptive immune systems, leading to immunosuppression of various effector functions. Numerous bioactive molecules secreted by MSCs, particularly cytokines, growth factors, and chemokines, exert autocrine/paracrine effects that modulate the physiological processes of MSCs. These invaluable virtues of MSCs provide new insight into potential treatments for tissue damage and inflammation. In particular, their extensive immunosuppressive properties are being explored for promising therapeutic application in immune disorders. Recently, clinical trials for MSC-mediated therapies have rapidly developed for immune-related diseases following reports from preclinical studies declaring their therapeutic safety and efficacy. Though immunotherapy of MSCs remains controversial, these clinical trials pave the way for their widespread therapeutic application in immune-based diseases. In this review, we will summarize and update the latest research findings and clinical trials on MSC-based immunomodulation.

scholarly journals Hypoxic mesenchymal stem cells ameliorate acute kidney ischemia-reperfusion injury via enhancing renal tubular autophagy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wei-Cheng Tseng ◽  
Pei-Ying Lee ◽  
Ming-Tsun Tsai ◽  
Fu-Pang Chang ◽  
Nien-Jung Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Recovery ◽  
Trophic Factors ◽  
Left Renal Artery ◽  
Renal Tubular Cells ◽  
Cell Based Therapy ◽  
Renal Tubular

Abstract Background Acute kidney injury (AKI) is an emerging global healthcare issue without effective therapy yet. Autophagy recycles damaged organelles and helps maintain tissue homeostasis in acute renal ischemia-reperfusion (I/R) injury. Hypoxic mesenchymal stem cells (HMSCs) represent an innovative cell-based therapy in AKI. Moreover, the conditioned medium of HMSCs (HMSC-CM) rich in beneficial trophic factors may serve as a cell-free alternative therapy. Nonetheless, whether HMSCs or HMSC-CM mitigate renal I/R injury via modulating tubular autophagy remains unclear. Methods Renal I/R injury was induced by clamping of the left renal artery with right nephrectomy in male Sprague-Dawley rats. The rats were injected with either PBS, HMSCs, or HMSC-CM immediately after the surgery and sacrificed 48 h later. Renal tubular NRK-52E cells subjected to hypoxia-reoxygenation (H/R) injury were co-cultured with HMSCs or treated with HMSC-CM to assess the regulatory effects of HSMCs on tubular autophagy and apoptosis. The association of tubular autophagy gene expression and renal recovery was also investigated in patients with ischemic AKI. Result HMSCs had a superior anti-oxidative effect in I/R-injured rat kidneys as compared to normoxia-cultured mesenchymal stem cells. HMSCs further attenuated renal macrophage infiltration and inflammation, reduced tubular apoptosis, enhanced tubular proliferation, and improved kidney function decline in rats with renal I/R injury. Moreover, HMSCs suppressed superoxide formation, reduced DNA damage and lipid peroxidation, and increased anti-oxidants expression in renal tubular epithelial cells during I/R injury. Co-culture of HMSCs with H/R-injured NRK-52E cells also lessened tubular cell death. Mechanistically, HMSCs downregulated the expression of pro-inflammatory interleukin-1β, proapoptotic Bax, and caspase 3. Notably, HMSCs also upregulated the expression of autophagy-related LC3B, Atg5 and Beclin 1 in renal tubular cells both in vivo and in vitro. Addition of 3-methyladenine suppressed the activity of autophagy and abrogated the renoprotective effects of HMSCs. The renoprotective effect of tubular autophagy was further validated in patients with ischemic AKI. AKI patients with higher renal LC3B expression were associated with better renal recovery. Conclusion The present study describes that the enhancing effect of MSCs, and especially of HMCSs, on tissue autophagy can be applied to suppress renal tubular apoptosis and attenuate renal impairment during renal I/R injury in the rat. Our findings provide further mechanistic support to HMSCs therapy and its investigation in clinical trials of ischemic AKI.

scholarly journals The Cross-Talk between Mesenchymal Stem Cells and Immune Cells in Tissue Repair and Regeneration

2021 ◽  
Vol 22 (5) ◽  
pp. 2472
Author(s):  
Carl Randall Harrell ◽  
Valentin Djonov ◽  
Vladislav Volarevic
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune Cells ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Multipotent Stem Cells ◽  
Tissue Repair And Regeneration ◽  
Almost All ◽  
And Function

Mesenchymal stem cells (MSCs) are self-renewable, rapidly proliferating, multipotent stem cells which reside in almost all post-natal tissues. MSCs possess potent immunoregulatory properties and, in juxtacrine and paracrine manner, modulate phenotype and function of all immune cells that participate in tissue repair and regeneration. Additionally, MSCs produce various pro-angiogenic factors and promote neo-vascularization in healing tissues, contributing to their enhanced repair and regeneration. In this review article, we summarized current knowledge about molecular mechanisms that regulate the crosstalk between MSCs and immune cells in tissue repair and regeneration.

scholarly journals Proteomic Analysis of the Secretome and Exosomes of Feline Adipose-Derived Mesenchymal Stem Cells

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 295
Author(s):  
Antonio J. Villatoro ◽  
María del Carmen Martín-Astorga ◽  
Cristina Alcoholado ◽  
María del Mar Sánchez-Martín ◽  
José Becerra
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Endocrine System ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Cell Junctions ◽  
Bioactive Molecules ◽  
Protein Protein Interaction ◽  
Cell Signaling Pathways

Mesenchymal stem cells (MSCs) have been shown to have therapeutic efficacy in different complex pathologies in feline species. This effect is attributed to the secretion of a wide variety of bioactive molecules and extracellular vesicles, such as exosomes, with significant paracrine activity, encompassed under the concept of the secretome. However, at present, the exosomes from feline MSCs have not yet been studied in detail. The objective of this study is to analyze and compare the protein profiles of the secretome as a whole and its exosomal fraction from feline adipose-derived MSCs (fAd-MSCs). For this, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Protein–Protein Interaction Networks Functional Enrichment Analysis (STRING) were utilized. A total of 239 proteins were identified in the secretome, and 228 proteins specific to exosomes were identified, with a total of 133 common proteins. The proteins identified in the secretome were located in the extracellular regions and in the cytoplasm, while the exosomal proteins were located mainly in the membrane, cytoplasm and cytosol. Regarding function, in the secretome, proteins involved in different metabolic pathways, in pathways related to the immune system and the endocrine system and in the processing of proteins in the endoplasmic reticulum predominated. In contrast, proteins specific to exosomes were predominantly associated with endocytosis, cell junctions, platelet activation and other cell signaling pathways. The possible future use of the secretome, or some of its components, such as exosomes, would provide a non-cell-based therapeutic strategy for the treatment of different diseases that would avoid the drawbacks of cell therapy.

Abstract MP243: Detection Of Mesenchymal Stem Cells In Mobilized Autologous Peripheral Blood Transplantation From Patients With Ischemic Heart Disease

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Hadyanto Lim ◽  
Umar Zein ◽  
Ilham Hariaji
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Peripheral Blood ◽  
Autologous Transplantation ◽  
White Blood Cells ◽  
Significant Rise ◽  
Ischemic Heart ◽  
Post Transplantation

Background: Mesenchymal stem cells (MSCs) improve the cardiac function and remodeling in patients with ischemic heart disease. However, their presence in the circulating peripheral blood and post-transplantation has not been fully elucidated. We aimed to investigate the effects of intravenous transplantation of mobilized autologous peripheral blood on the number of MSCs in patients with ischemic heart disease. Methods: Granulocyte-colony stimulating factor (G-CSF, 5.0 μg/kg/day) was given subcutaneously once a day for five days to 7 patients (4 women and 3 men, aged 54-69 years) with ischemic heart disease. Leukapheresis procedure was started on the day 5 of G-CSF using the Spectra Optia cell separator. Circulating and intravenous transplantation of autologous MSCs after leukapheresis were analyzed by flow cytometry. MSCs were identified on the basis of dual positive cells (CD73 + /CD105 + or CD90 + /CD73 + or CD90 + /CD105 + ) and detected as MSCs if a cluster of at least 10 cells could be found. Results: MSCs in the circulating peripheral blood and after transplantation were detected in 2 (28%) and 6 (85%) patients, respectively. The frequency of intravenous peripheral blood MSCs increased significantly after transplantation (from 32.57 ± 22.76 x10 -4 % to 58.57 ± 28.49 x 10 -4 % , p<0.001). Moreover, there were significant rise in the total white blood cells count (from 10.25 ± 4.86 x 10 3 /μl to 35.81 ± 7.07 x 10 3 /μl, p<0.001) and the levels of CD34 + cells (from 1.17 ± 0.93 cells/μL to 138.30 ± 11.26 cells/μL, p<0.001) after the infusion. Conclusions: The results show that intravenous transplantation of mobilized autologous peripheral blood increases the number of MSCs in patients with ischemic heart disease. Leukapheresis product of peripheral blood MSCs could therefore be a potential source for autologous transplantation in ischemic heart disease.

Migration of Human Mesenchymal Stem Cells is Stimulated by Low Shear Stress via MAPK Signaling

2012 ◽  
Author(s):  
Lin Yuan ◽  
Naoya Sakamoto ◽  
Guanbin Song ◽  
Masaaki Sato
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Mapk Signaling ◽  
Disease Treatment ◽  
Differentiation Potential ◽  
Multipotent Stem Cells ◽  
Low Shear Stress ◽  
Multipotent Differentiation ◽  
And Migration

Mesenchymal stem cells (MSCs) represent as multipotent stem cells which hold the abilities of self-renewal and give rise to cells of diverse lineages [1]. With their remarkable combination of multipotent differentiation potential and low immunogenicity, MSCs are considered to be an attractive candidate for cell-based tissue repair and regenerative tissue engineering [2, 3]. Increasing number of studies has demonstrated that mobilization and migration of injected MSCs to the damaged tissues is a key step for these cells to participate in disease treatment and tissue regeneration [4, 5].

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