Msc In Stem Cells And Regenerative Medicine – González-González A, García-Sánchez D, Dotta M, Rodríguez-Rey JC, Pérez-Campo FM Mesenchymal stem cell secretome: a cornerstone of cell-free regenerative medicine. World J Stem Cell 2020;12(12): [15529. PMID: 33505599 DOI: 10.4252/wjsc.v12.i12.1529]
Flor M Pérez-Campo, BSc, MSc, PhD, Assistant Professor, Senior Scientist, Department of Molecular Biology_IDIVAL, Faculty of Medicine, University of Cantabria, Avda Cardenal Herrera Oria S/N, Santander 39011, Cantabria, Spain. f.perezcampo@unican.es
Msc In Stem Cells And Regenerative Medicine
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Stem Cell Therapy Protects Against The Side Effects Of Cancer Drugs
Alberto Gonzalez-González, Daniel García-Sánchez, Monica Dotta, José C Rodríguez-Rey, Flor M Pérez-Campo, Department of Molecular Biology_IDIVAL, Faculty of Medicine, University of Cantabria, Santander 39011, Cantabria, Spain
ORCID Number: Alberto Gonzalez-Gonzalez (0000-0002-2336-8284); Daniel Garcia-Sanchez (0000-0002-1754-9185); Monica Dota (0000-0003-2719-0564); Jose Kay Rodriguez-Rey (0000-0002-8369-3118); Flor M Perez-Campo (0000-0002-9872-7990).
Author Contributions: Gonzalez-Gonzalez A, García-Sanchez D, Dotta M, Rodriguez-Rey JC and Pérez-Campo FM wrote and approved the final version of the manuscript.
Open Access: This article is an open access article selected by an internal editor and thoroughly reviewed by external reviewers. It is distributed under the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) license, which allows others to distribute, remix, adapt, non-commercially exploit this work, and license their derivative works under various conditions. , provided that the original work is properly cited and the use is not commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Stem Cell Technology And Regenerative Medicines 2012 2013 M.sc Biotechnology Semester 4 Question Paper With Pdf Download
Corresponding author: Flor M Pérez-Campo, BSc, MSc, PhD, Associate Professor, Senior Scientist, Department of Molecular Biology_IDIVAL, Faculty of Medicine, University of Cantabria, Avda Cardenal Herrera Oria S/N, Santander 39011, Cantabria.
Mesenchymal stem cells (MSCs) are the most commonly used stem cells in clinical trials because of their easy isolation from various adult tissues, their ability to enter sites of injury, and their ability to differentiate into multiple cell types. However, the realization that the beneficial effects of MSCs depend mainly on their paracrine effects rather than their entry and subsequent differentiation into recipient tissues opened the way for cell-free therapeutic strategies in regenerative medicine. All soluble factors and vesicles secreted by MSCs are known as secretions. MSC secretion plays a central role in cell-to-cell communication and has been shown to be an active mediator of immunomodulation and regeneration both in vitro and in vivo. In addition, the use of secretome has major advantages over cell therapy, such as low immunogenicity and ease of production, processing, and storage. Importantly, MSCs can be modulated to alter their secretory composition to better suit specific therapeutic targets, thus opening up many possibilities. Taken together, these advantages now place MSC secretion at the center of many studies in various clinical contexts, enabling rapid scientific progress in this field.
Key tip: Mesenchymal stem cells (MSCs) produce large numbers of bioactive molecules and extracellular vesicles known as secretomes that exert important paracrine effects on neighboring cells and tissues. The use of MSC secretion in tissue regeneration therapies may prevent problems associated with MSC-based therapies, such as low cell survival and engraftment, which significantly limit their therapeutic efficacy, or negative side effects associated with the use of these cells.
Over the past few years, mesenchymal stem/stromal cells (MSCs) have emerged as a promising therapeutic option that has been the focus of many studies in the field of regenerative medicine. This particular type of stem cell has unique properties that make it a valuable tool for tissue regeneration. MSCs are fibroblast-like cells found in various mature tissues that have maintained a high level of plasticity and are capable of differentiating into various mesodermal, ectodermal and endodermal lineages[1]. Although it was the differentiation potential and ability to localize to sites of injury that initially attracted the interest of the scientific community, the regenerative capacity of MSCs in general has proven to be very limited, especially in pathological settings. MSCs are present in many tissues, but in very small numbers, so a period of expansion after harvest is necessary to allow the number of cells required for subsequent processing. Even when this expansion step is successful and a large number of cells are transplanted in the process, the cells often have significantly reduced viability and low engraftment in the recipient tissue[2]. Factors such as age of the donor, number of passages during in vitro expansion, culture conditions, procedure of administration and the pathological microenvironment encountered by the transplant cells adversely affect the ability of the cells to survive and engraft in the recipient tissue. . Even after successful transplantation, MSCs appear unable to properly direct angiogenesis, a critical step for successful tissue regeneration[3]. Currently, many studies are trying to overcome these drawbacks by genetically modifying MSCs and optimizing their culture conditions[4], but overall, there are still important limitations regarding the biosafety of MSCs. Recent studies have shown potential tumorigenesis and risk of infection of MSCs during the isolation and administration process[5, 6], the possibility of zoonotic disease transmission due to the use of fetal bovine serum during the in vitro expansion phase[7]. , their potential profibrogenic potential related to pulmonary entrapment after systemic MSC administration[8,9] and the heterogeneity of MSC populations in terms of embolism and differentiation potential[10]. Despite all the limitations related to therapeutic procedures using MSCs, these cells can still be very useful in the field of regenerative medicine due to other important properties. Although initially the methods regarding MSCs in tissue engineering were based on their cellular aspects, several studies now confirm that the beneficial effects of transplanted MSCs reported in some applications are related to their important paracrine activity and not to their ability to differentiate into specific cells. Lineage In fact, up to 80% of the regenerative capacity of transplanted MSCs is due to this paracrine activity[11]. MSCs produce and secrete various bioactive molecules in response to various microenvironmental conditions and are also called “trophic factories”. The combination of all trophic factors or molecules secreted by these cells into the extracellular space is known as secretion. The term secretion includes two distinct components: the soluble fraction, which mainly includes cytokines, chemokines, immunomodulatory molecules, and growth factors[12], and the vesicular fraction, which includes various types of vesicles, which play a key role in microRNA delivery. . . and proteins involved in cell-to-cell communication[13].
Stem Cell Therapy: A Comprehensive Overview (2023)
The use of MSC-derived secretions in tissue engineering has several important advantages over the use of stem cells[14]. First, it avoids the surgical intervention and associated risks required to obtain the cells as well as the subsequent expansion of these cells in vitro. Second, the use of secretome also overcomes all of the aforementioned disadvantages associated with MSC administration. Additionally, Secretome can be considered a pharmaceutical drug and therefore evaluated in the same way in terms of dosage and safety. Most importantly, however, the composition of the secretion is specifically influenced by the various stimuli present in the microenvironment, allowing us to modify it to better suit specific therapeutic targets.
Although studies on the regenerative potential of MSC secretion are few compared to studies on the regenerative potential of MSCs, preclinical studies to date have shown significant positive results and few negative effects associated with the use of this product. The aim of this review is to evaluate the role of MSC secretion as the main driver of their regenerative activity, describe the main components of the soluble and vesicular fractions and the main biological processes in tissue regeneration that are positively influenced by these bioactive components.
MSCs are capable of secreting a variety of autocrine and paracrine factors, including cytokines, chemokines, extracellular matrix (ECM) proteases, and growth factors, allowing their use as a potential source of cell-free therapy[ 15 ]. Biomolecules derived from bone marrow (BM) MSCs have been extensively studied to better elucidate their potential[ 16 ]. In fact, proteomic analysis has revealed the presence of up to 1533 proteins [17, 18] participating in various biological processes. A summary of this information is shown in Figure 1.
HGF: hepatocyte growth factor; TGF-β: transforming growth factor-β; IDO: Indoleamine 2,3-dioxygenase; PGE2: prostaglandin E2; IL: interleukin; DC: dendritic cells; CCL: CC-chemokine ligand; NK: natural killer cells; MSC: mesenchymal stem cells; CXCR: C-X-C type chemokine receptor; VEGF: vascular endothelial growth factor; IGF: insulin-like growth factor; FGF: fibroblast growth factor; Nrf2: nuclear factor erythroid-related factor 2; HIF: hypoxia-inducible factor; SDF: stromal cell factor; PDGF: platelet-derived growth factor; ANG1: angiogenesis 1; MCP-1: monocyte chemotactic protein-1; ROS: reactive oxygen species; hCAP: human cathelicidin antimicrobial peptide; HO-1: heme oxygenase; NO: Nitrous oxide. This figure was created by Biorender.com.
Primary Cells In Stem Cells & Regenerative Medicine
MSCs are able to influence the innate and adaptive responses of the immune system to various stimuli as well as the secretion of specific factors through cell exposure. There is increasing evidence of an association between soluble factors of MSCs and cells of the immune system, such as lymphocytes, dendritic cells (DC), natural killer (NK) cells, and macrophages.
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