scholarly journals Secretion, migration and adhesion as key processes in the therapeutic activity of mesenchymal stem cells

2019 ◽  
Author(s):  
Marta Kot ◽  
Aleksandra Musiał-Wysocka ◽  
Małgorzata Lasota ◽  
Aleksandra Ulman ◽  
Marcin Majka
Keyword(s):  
Stem Cells ◽  
Cell Communication ◽  
Bioactive Molecules ◽  
Key Factors ◽  
Paracrine Effects ◽  
Factors Affecting ◽  
Physiological Processes ◽  
Therapeutic Benefits ◽  
Remote Sites ◽  
Immature Cells

The MSCs are immature cells that can be found in numerous different tissue types. In recent years, they have gained considerable attention, particularly with regard to their regenerative properties. Due to their paracrine activity, ability to migrate, adhesion and homing, MSCs currently appear to be the most relevant for therapeutic use. Numerous bioactive molecules secreted by MSCs exert paracrine effects and modulate many physiological processes, such as angiogenesis, immunomodulation and neuroprotection. Cell-cell communication may be also mediated by extracellular vesicles released from the cells. Due to these properties, MSCs have been widely studied for evaluation of their therapeutic benefits expected in the clinical applications. For effective tissue regeneration, transplanted MSCs have to exit the circulation and locate at the site of damage, which is possible because of their ability to migrate, adhere and engraft at the target site. Accumulating evidence suggests that MSCs recruitment from remote sites is similar to leukocytes’ migration. All of these biological features make MSCs highly investigated stem cells and the most commonly used cells in regenerative medicine. Since environmental factors affect the MSCs behavior, we discuss importance of oxygen concentration as a one of the key factors affecting MSCs properties.

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 Therapeutic Properties of Mesenchymal Stromal/Stem Cells: The Need of Cell Priming for Cell-Free Therapies in Regenerative Medicine

2021 ◽  
Vol 22 (2) ◽  
pp. 763
Author(s):  
Vitale Miceli ◽  
Matteo Bulati ◽  
Gioacchin Iannolo ◽  
Giovanni Zito ◽  
Alessia Gallo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Tissue Regeneration ◽  
Adult Stem Cells ◽  
Bioactive Molecules ◽  
Therapeutic Effects ◽  
Therapeutic Benefits ◽  
Therapeutic Properties ◽  
Stromal Stem Cells ◽  
Stimulation Of

Mesenchymal stromal/stem cells (MSCs) are multipotent adult stem cells that support homeostasis during tissue regeneration. In the last decade, cell therapies based on the use of MSCs have emerged as a promising strategy in the field of regenerative medicine. Although these cells possess robust therapeutic properties that can be applied in the treatment of different diseases, variables in preclinical and clinical trials lead to inconsistent outcomes. MSC therapeutic effects result from the secretion of bioactive molecules affected by either local microenvironment or MSC culture conditions. Hence, MSC paracrine action is currently being explored in several clinical settings either using a conditioned medium (CM) or MSC-derived exosomes (EXOs), where these products modulate tissue responses in different types of injuries. In this scenario, MSC paracrine mechanisms provide a promising framework for enhancing MSC therapeutic benefits, where the composition of secretome can be modulated by priming of the MSCs. In this review, we examine the literature on the priming of MSCs as a tool to enhance their therapeutic properties applicable to the main processes involved in tissue regeneration, including the reduction of fibrosis, the immunomodulation, the stimulation of angiogenesis, and the stimulation of resident progenitor cells, thereby providing new insights for the therapeutic use of MSCs-derived products.

scholarly journals Exosomes and Their Therapeutic Potentials of Stem Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Chao Han ◽  
Xuan Sun ◽  
Ling Liu ◽  
Haiyang Jiang ◽  
Yan Shen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Therapeutic Potential ◽  
Cell Communication ◽  
Cell Types ◽  
Specific Cell ◽  
Paracrine Factors ◽  
Paracrine Effects ◽  
Positive Effects ◽  
Stem And Progenitor Cells ◽  
Main Components

Exosomes, a group of vesicles originating from the multivesicular bodies (MVBs), are released into the extracellular space when MVBs fuse with the plasma membrane. Numerous studies indicate that exosomes play important roles in cell-to-cell communication, and exosomes from specific cell types and conditions display multiple functions such as exerting positive effects on regeneration in many tissues. It is widely accepted that the therapeutic potential of stem cells may be mediated largely by the paracrine factors, so harnessing the paracrine effects of stem and progenitor cells without affecting these living, replicating, and potentially pluripotent cell populations is an advantage in terms of safety and complexity. Ascending evidence indicated that exosomes might be the main components of paracrine factors; thus, understanding the role of exosomes in each subtype of stem cells is far-reaching. In this review, we discuss the functions of exosomes from different types of stem cells and emphasize the therapeutic potentials of exosomes, providing an alternative way of developing strategies to cure diseases.

scholarly journals Cre mRNA Is Not Transferred by EVs from Endothelial and Adipose-Derived Stromal/Stem Cells during Vascular Network Formation

2021 ◽  
Vol 22 (8) ◽  
pp. 4050
Author(s):  
Jaana Schneider ◽  
Marianne Pultar ◽  
Johannes Oesterreicher ◽  
Madhusudhan Reddy Bobbili ◽  
Severin Mühleder ◽  
...  
Keyword(s):  
Stem Cells ◽  
Network Formation ◽  
Cell Communication ◽  
Functional System ◽  
Vascular Network ◽  
Bioactive Molecules ◽  
Reporter System ◽  
Specific Loading ◽  
Stromal Stem Cells

Coculture systems employing adipose tissue-derived mesenchymal stromal/stem cells (ASC) and endothelial cells (EC) represent a widely used technique to model vascularization. Within this system, cell–cell communication is crucial for the achievement of functional vascular network formation. Extracellular vesicles (EVs) have recently emerged as key players in cell communication by transferring bioactive molecules between cells. In this study we aimed to address the role of EVs in ASC/EC cocultures by discriminating between cells, which have received functional EV cargo from cells that have not. Therefore, we employed the Cre-loxP system, which is based on donor cells expressing the Cre recombinase, whose mRNA was previously shown to be packaged into EVs and reporter cells containing a construct of floxed dsRed upstream of the eGFP coding sequence. The evaluation of Cre induced color switch in the reporter system via EVs indicated that there is no EV-mediated RNA transmission either between EC themselves or EC and ASC. However, since Cre mRNA was not found present in EVs, it remains unclear if Cre mRNA is generally not packaged into EVs or if EVs are not taken up by the utilized cell types. Our data indicate that this technique may not be applicable to evaluate EV-mediated cell-to-cell communication in an in vitro setting using EC and ASC. Further investigations will require a functional system showing efficient and specific loading of Cre mRNA or protein into EVs.

Immunotherapy: a potential approach to targeting cancer stem cells

2020 ◽  
Vol 20 ◽  
Author(s):  
Wenjun Wang ◽  
Ling Bai ◽  
Dongsheng Xu ◽  
Wei Li ◽  
Jiuwei Cui
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Tumor Recurrence ◽  
Immune Cell ◽  
Key Factors ◽  
Cell Therapies ◽  
Factors Affecting ◽  
Therapeutic Milieu ◽  
Traditional Therapies

: Tumor recurrence and drug resistance are two of the key factors affecting the prognosis of cancer patients. Cancer stem cells (CSCs) are a group of cells with infinite proliferation potential which are not sensitive to traditional therapies including radio- and chemotherapy. These CSCs are considered to be central to tumor recurrence and the development of drug resistance. In addition, CSCs are important targets in cancer immunotherapy because of their expression of novel tumor-associated antigens, which result from mutations in cancer cells over the course of treatment. Emerging immunotherapies, including cancer vaccines, checkpoint blockade therapies, and transferred immune cell therapies, have all been shown to be more effective when they selectively target CSCs. Such therapies may also provide novel additions to the current therapeutic milieu and may offer new therapeutic combinations for treatment. This review summarizes the relationships between various immunotherapies and CSCs and provides novel insights into potential therapeutic applications for these approaches in the future.

scholarly journals Adipose-Derived Stem Cells in Bone Tissue Engineering: Useful Tools with New Applications

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Gabriele Storti ◽  
Maria Giovanna Scioli ◽  
Bong-Sung Kim ◽  
Augusto Orlandi ◽  
Valerio Cervelli
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Bioactive Molecules ◽  
Adipose Derived Stem Cells ◽  
Paracrine Effects ◽  
Cell Subpopulations ◽  
New Applications ◽  
Host Tissues

Adipose stem cells (ASCs) are a crucial element in bone tissue engineering (BTE). They are easy to harvest and isolate, and they are available in significative quantities, thus offering a feasible and valid alternative to other sources of mesenchymal stem cells (MSCs), like bone marrow. Together with an advantageous proliferative and differentiative profile, they also offer a high paracrine activity through the secretion of several bioactive molecules (such as growth factors and miRNAs) via a sustained exosomal release which can exert efficient conditioning on the surrounding microenvironment. BTE relies on three key elements: (1) scaffold, (2) osteoprogenitor cells, and (3) bioactive factors. These elements have been thoroughly investigated over the years. The use of ASCs has offered significative new advancements in the efficacy of each of these elements. Notably, the phenotypic study of ASCs allowed discovering cell subpopulations, which have enhanced osteogenic and vasculogenic capacity. ASCs favored a better vascularization and integration of the scaffolds, while improvements in scaffolds’ materials and design tried to exploit the osteogenic features of ASCs, thus reducing the need for external bioactive factors. At the same time, ASCs proved to be an incredible source of bioactive, proosteogenic factors that are released through their abundant exosome secretion. ASC exosomes can exert significant paracrine effects in the surroundings, even in the absence of the primary cells. These paracrine signals recruit progenitor cells from the host tissues and enhance regeneration. In this review, we will focus on the recent discoveries which have involved the use of ASCs in BTE. In particular, we are going to analyze the different ASCs’ subpopulations, the interaction between ASCs and scaffolds, and the bioactive factors which are secreted by ASCs or can induce their osteogenic commitment. All these advancements are ultimately intended for a faster translational and clinical application of BTE.

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.

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