Abstract Mesenchymal stem cells (MSCs) can be widely isolated from various tissues including bone marrow, umbilical cord, and adipose tissue, with the potential for self-renewal and multipotent differentiation. There is compelling evidence that the therapeutic effect of MSCs mainly depends on their paracrine action. Extracellular vesicles (EVs) are fundamental paracrine effectors of MSCs and play a crucial role in intercellular communication, existing in various body fluids and cell supernatants. Since MSC-derived EVs retain the function of protocells and have lower immunogenicity, they have a wide range of prospective therapeutic applications with advantages over cell therapy. We describe some characteristics of MSC-EVs, and discuss their role in immune regulation and regeneration, with emphasis on the molecular mechanism and application of MSC-EVs in the treatment of fibrosis and support tissue repair. We also highlight current challenges in the clinical application of MSC-EVs and potential ways to overcome the problem of quality heterogeneity. 

/pdf/mesenchymal-stem-cell-derived-extracellular-vesicles-for-3q9dsevv.pdf

Mesenchymal stem cell-derived extracellular vesicles for immunomodulation and regeneration: a next generation therapeutic tool?

Ischemic stroke is one of the major causes of death and disability in the world. Currently, most patients cannot choose intravenous thrombolysis or intravascular mechanical thrombectomy because of narrow therapeutic windows and severe complications. Stem cell transplantation is an emerging treatment and has been studied in various central nervous system diseases. Animal and clinical studies showed that transplantation of mesenchymal stem cells (MSCs) could alleviate neurological deficits and bring hope for ischemic stroke treatment. This article reviewed biological characteristics, safety, feasibility and efficacy of MSCs therapy, potential therapeutic targets of MSCs, and production process of Good Manufacturing Practices-grade MSCs, to explore the potential therapeutic targets of MSCs in the process of production and use and provide new therapeutic directions for ischemic stroke. 

/pdf/potential-mechanisms-and-therapeutic-targets-of-mesenchymal-24oldsl5.pdf

Potential mechanisms and therapeutic targets of mesenchymal stem cell transplantation for ischemic stroke

Mesenchymal stromal cell (MSC) therapy has seen increased attention as a possible option to treat a number of inflammatory conditions including COVID-19 acute respiratory distress syndrome (ARDS). As rates of obesity and metabolic disease continue to rise worldwide, increasing proportions of patients treated with MSC therapy will be living with obesity. The obese environment poses critical challenges for immunomodulatory therapies that should be accounted for during development and testing of MSCs. In this review, we look to cancer immunotherapy as a model for the challenges MSCs may face in obese environments. We then outline current evidence that obesity alters MSC immunomodulatory function, drastically modifies the host immune system, and therefore reshapes interactions between MSCs and immune cells. Finally, we argue that obese environments may alter essential features of allogeneic MSCs and offer potential strategies for licensing of MSCs to enhance their efficacy in the obese microenvironment. Our aim is to combine insights from basic research in MSC biology and clinical trials to inform new strategies to ensure MSC therapy is effective for a broad range of patients.

/pdf/translating-msc-therapy-in-the-age-of-obesity-3u5f2lcg.pdf

Translating MSC Therapy in the Age of Obesity

Abstract Potency analysis of mesenchymal stromal cells (MSCs) is required for their use in advanced clinical trials. Assay matrix strategy evaluating more than a single property of MSCs is an emerging strategy in potency analysis. Here we developed an assay matrix approach focusing on the secretory chemokine responses of MSCs using multiplex analytical method. MSCs’ innate fitness in secreting matrix of chemokines is correlated with their metabolic fitness in differential degrees. In addition, innately secreting chemokines are correlated among themselves in a unique pattern. MSC’s matrix chemokine responses to exogenous stimulation of IFNγ and/or TNFα are distinct. However, the combination of IFNγ and TNFα is superior than individual stimulations in eliciting robust and broad matrix chemokine responses of MSCs. Correlation matrix analysis has identified that chemokine responses to IFNγ and/or TNFα display unique correlative secretion patterns. MSC and peripheral blood mononuclear cells coculture analysis has identified the correlation matrix responses of chemokines that predicted immune suppression. In addition, MSC-mediated blocking of T-cell proliferation predominantly correlates with chemokines in an inverse manner. Knockdown of chemokines has demonstrated that MSC-sourced inherent chemokines do not actively play a role in T-cell suppression and thus are the bystander predictors of T-cell suppression. The present analysis of MSC’s matrix chemokine responses can be deployed in the advanced potency analysis of MSCs.

/pdf/chemokine-assay-matrix-defines-the-potency-of-human-bone-hj844fqb.pdf

Chemokine Assay Matrix Defines the Potency of Human Bone Marrow Mesenchymal Stromal Cells

The therapeutic efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is limited by the development of graft-versus-host disease (GVHD). In GVHD, rigorous pre-conditioning regimen resets the immune landscape and inflammatory milieu causing immune dysregulation, characterized by an expansion of alloreactive cells and a reduction in immune regulatory cells. In acute GVHD (aGVHD), the release of damage- and pathogen- associated molecular patterns from damaged tissue caused by the conditioning regimen sets the stage for T cell priming, activation and expansion further exacerbating tissue injury and organ damage, particularly in the gastrointestinal tract. Studies have shown that donor T cells utilize multiple energetic and biosynthetic pathways to mediate GVHD that can be distinct from the pathways used by regulatory T cells for their suppressive function. In chronic GVHD (cGVHD), donor T cells may differentiate into IL-21 producing T follicular helper cells or tissue resident T helper cells that cooperate with germinal center B cells or memory B cells, respectively, to produce allo- and auto-reactive antibodies with subsequent tissue fibrosis. Alternatively, donor T cells can become IFN- γ/IL-17 cytokine expressing T cells that mediate sclerodermatous skin injury. Patients refractory to the first line standard regimens for GVHD treatment have a poor prognosis indicating an urgent need for new therapies to restore the balance between effector and regulatory immune cells while preserving the beneficial graft-versus-tumor effect. Emerging data points toward a role for metabolism in regulating these allo- and auto-immune responses. Here, we will discuss the preclinical and clinical data available on the distinct metabolic demands of acute and chronic GVHD and recent efforts in identifying therapeutic targets using metabolomics. Another dimension of this review will examine the changing microbiome after allo-HSCT and the role of microbial metabolites such as short chain fatty acids and long chain fatty acids on regulating immune responses. Lastly, we will examine the metabolic implications of coinhibitory pathway blockade and cellular therapies in allo-HSCT. In conclusion, greater understanding of metabolic pathways involved in immune cell dysregulation during allo-HSCT may pave the way to provide novel therapies to prevent and treat GVHD.

/pdf/recent-metabolic-advances-for-preventing-and-treating-acute-e2vpmqnq46.pdf

Recent Metabolic Advances for Preventing and Treating Acute and Chronic Graft Versus Host Disease.

Acute graft-vs.-host (GVHD) disease remains a common complication of allogeneic stem cell transplantation with very poor outcomes once the disease becomes steroid refractory. Mesenchymal stem cells (MSCs) represent a promising therapeutic approach for the treatment of GVHD, but so far this strategy has had equivocal clinical efficacy. Therapies using MSCs require optimization taking advantage of the plasticity of these cells in response to different microenvironments. In this study, we aimed to optimize cord blood tissue derived MSCs (CBti MSCs) by priming them using a regimen of inflammatory cytokines. This approach led to their metabolic reprogramming with enhancement of their glycolytic capacity. Metabolically reprogrammed CBti MSCs displayed a boosted immunosuppressive potential, with superior immunomodulatory and homing properties, even after cryopreservation and thawing. Mechanistically, primed CBti MSCs significantly interfered with glycolytic switching and mTOR signaling in T cells, suppressing T cell proliferation and ensuing polarizing toward T regulatory cells. Based on these data, we generated a Good Manufacturing Process (GMP) Laboratory protocol for the production and cryopreservation of primed CBti MSCs for clinical use. Following thawing, these cryopreserved GMP-compliant primed CBti MSCs significantly improved outcomes in a xenogenic mouse model of GVHD. Our data support the concept that metabolic profiling of MSCs can be used as a surrogate for their suppressive potential in conjunction with conventional functional methods to support their therapeutic use in GVHD or other autoimmune disorders.

/pdf/metabolic-reprogramming-of-gmp-grade-cord-tissue-derived-5bjebvd86o.pdf

Metabolic Reprogramming of GMP Grade Cord Tissue Derived Mesenchymal Stem Cells Enhances Their Suppressive Potential in GVHD.

/pdf/harnessing-the-metabolic-vulnerabilities-of-leukemia-stem-2xbw1936er.pdf

Harnessing the Metabolic Vulnerabilities of Leukemia Stem Cells to Eradicate Acute Myeloid Leukemia.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Bijender Kumar

Author Tools

Chat about Author

Papers

Metabolic Reprogramming of GMP Grade Cord Tissue Derived Mesenchymal Stem Cells Enhances Their Suppressive Potential in GVHD.

Harnessing the Metabolic Vulnerabilities of Leukemia Stem Cells to Eradicate Acute Myeloid Leukemia.