Review
Cell Biology
Jingyi Cai, Hexu Qi, Ke Yao, Yang Yao, Dian Jing, Wen Liao, Zhihe Zhao
Summary: The desire to delay or even reverse aging has never diminished. Mesenchymal stem cells (MSCs) with unique abilities are highlighted, but their senescence can lead to age-related diseases or compromised therapeutic outcomes. Non-coding RNAs (ncRNAs) play a crucial role in regulating cellular fate, and a systematic exploration of ncRNAs steering MSCs during senescence is urgently needed. This review discusses the relationship between senescence and MSCs, the role of ncRNAs in MSC senescence, and the clinical applications of ncRNA-based therapies in MSC-related fields.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Sevindzh Kletukhina, Guzel Mutallapova, Angelina Titova, Marina Gomzikova
Summary: Idiopathic pulmonary fibrosis (IPF) is a progressive disease caused by the aberrant regeneration of pulmonary epithelium. Mesenchymal stem cells (MSCs) and extracellular vesicles (EVs) are promising therapies for pulmonary fibrosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biotechnology & Applied Microbiology
Richard Jeske, Xingchi Chen, Shaoyang Ma, Eric Z. Zeng, Tristan Driscoll, Yan Li
Summary: This study compares the effects of different carriers on the growth of hASCs in a spinner flask bioreactor system and traditional 2D culture. The results show that the microenvironment in the spinner flask bioreactor enhances the stemness, metabolism, and cytokine secretion of hASCs, as well as increases the production of extracellular vesicles.
BIOCHEMICAL ENGINEERING JOURNAL
(2022)
Review
Biochemistry & Molecular Biology
Virinder Kaur Sarhadi, Ravindra Daddali, Riitta Seppanen-Kaijansinkko
Summary: Osteosarcoma is an aggressive bone tumor that predominantly affects children and adolescents, with a strong tendency to relapse and metastasize, posing challenges in identifying new therapeutic targets. Mesenchymal stem cells play a significant role in osteosarcoma development, contributing to tumor progression through intercellular signaling and communication.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell & Tissue Engineering
Yuling Huang, Lina Yang
Summary: MSC-EVs have demonstrated significant therapeutic effects on acute kidney injury, chronic kidney disease, diabetic nephropathy, and atherosclerotic renovascular disease, while their roles in transplanted kidneys remain controversial.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Biotechnology & Applied Microbiology
Mustafa Burak Acar, Serife Ayaz-Guner, Zeynep Gunaydin, Musa Karakukcu, Gianfranco Peluso, Giovanni Di Bernardo, Servet Ozcan, Umberto Galderisi
Summary: Senotherapeutics, including senolytics and senomorphics, can delay replicative senescence and cell death, improving cell function through specific pathways. Metformin, a potential senomorphic agent, may exert its effects by scavenging ROS and regulating key transcription factors involved in blocking oxidative stress.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Review
Cell & Tissue Engineering
Ali Rajool Dezfuly, Azadeh Safaee, Hossein Salehi
Summary: Extracellular vesicles (EVs), including microvesicles and exosomes, carry vital information such as lipids, proteins, mRNAs, and microRNAs to target cells. Studies have shown that the therapeutic effects of stem cells are attributed to the miRNAs in their EVs, which may help in developing new therapeutic techniques for retinal degenerative diseases.
STEM CELL RESEARCH & THERAPY
(2021)
Review
Pharmacology & Pharmacy
Jafar Rezaie, Vahid Nejati, Monireh Mahmoodi, Mahdi Ahmadi
Summary: Extracellular vesicles (EVs), particularly MSCs-EVs, have shown great potential as a drug delivery system in nanomedicine. They can selectively deliver therapeutic agents to target cells and improve various diseases. However, there are still challenges that need to be addressed for the clinical translation of modified MSCs-EVs.
BIOCHEMICAL PHARMACOLOGY
(2022)
Review
Cell Biology
Hilal Ahmad Rather, Sameh Almousa, Suzanne Craft, Gagan Deep
Summary: Extracellular vesicles (EVs) are heterogeneous nanovesicles secreted by cells for intercellular communication and maintaining cellular homeostasis. Stem cell-derived EVs (SC-EVs) have shown therapeutic benefits in aging-related pathologies and neurodegenerative diseases like Alzheimer's.
AGEING RESEARCH REVIEWS
(2023)
Article
Endocrinology & Metabolism
Matthew L. Potter, William D. Hill, Carlos M. Isales, Mark W. Hamrick, Sadanand Fulzele
Summary: miRNAs and cellular senescence have been implicated in driving age-related diseases, particularly in mesenchymal stem cells. Differential expression of key miRNAs in MSCs and other musculoskeletal cells during senescence and aging, regulation of miRNAs via SASP cytokines, and targeting of components of cell cycle arrest pathways by miRNAs have been identified. Identifying potential miRNA targets may have implications for regenerative medicine applications in age-related musculoskeletal diseases.
Review
Immunology
Sylwia Dabrowska, Anna Andrzejewska, Miroslaw Janowski, Barbara Lukomska
Summary: Mesenchymal stem cells (MSCs) possess supportive, differentiating, and immunoregulatory functions, while the extracellular vesicles (EVs) they produce can serve as a potential cellular therapy tool.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biotechnology & Applied Microbiology
Yuling Huang, Xin Li, Lina Yang
Summary: Hydrogels, as representatives of biomaterials, have attracted much attention in the medical field. This review studies the safety and feasibility of hydrogel-encapsulated mesenchymal stem cells (MSCs), as well as the enhancement of therapeutic effect through hydrogels.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Oncology
Narjara Gonzalez Suarez, Yuniel Fernandez-Marrero, Mathieu P. A. Hebert, Marie-Eve Roy, Luc H. Boudreau, Borhane Annabi
Summary: This study aimed to investigate the regulatory effect of green tea polyphenol EGCG on extracellular vesicles (EVs) in triple-negative breast cancer cells' secretome. The research found that EGCG significantly modified the genetic material of EVs under low oxygen conditions, reduced the ability of cancer cells to induce inflammation in adipose-derived mesenchymal stem cells (hADMSC), and decreased the mitochondrial content in cancer cell-derived EVs.
CANCER CELL INTERNATIONAL
(2023)
Review
Cell & Tissue Engineering
Liangrui Chen, Shasha Zhu, Shujuan Guo, Weidong Tian
Summary: Periodontitis is a common oral disease that causes damage to both hard and soft tissues of the periodontium, leading to tooth mobility and loss. Mesenchymal stem cells (MSCs) have emerged as a promising therapy for periodontitis due to their unique characteristics. Accumulating evidence suggests that the regenerative effects of MSCs are mainly mediated through paracrine signaling, including the release of extracellular vesicles (EVs) that contain bioactive substances. These MSC-EVs play a crucial role in regulating the biological functions of periodontal tissue cells, immune cells, and the local microenvironment, promoting tissue regeneration and repair. As a cell-free therapy, MSC-EVs offer advantages in terms of stability, immune rejection, and ethical concerns, making them potentially valuable for clinical applications in periodontal regeneration.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Chemistry, Multidisciplinary
Liming Li, Jiafu Mu, Yu Zhang, Chenyang Zhang, Teng Ma, Lu Chen, Tianchen Huang, Jiahe Wu, Jian Cao, Shiqing Feng, Youzhi Cai, Min Han, Jianqing Gao
Summary: This study found that exosomes derived from hypoxic preconditioned human umbilical vein endothelial cells can stimulate angiogenic MSCs, showing great potential in the treatment of traumatic spinal cord injury.
Article
Orthopedics
Shipin Zhang, Keng Lin Wong, Xiafei Ren, Kristeen Ye Wen Teo, Hassan Afizah, Andre Boon Hwa Choo, Ruenn Chai Lai, Sai Kiang Lim, James Hoi Po Hui, Wei Seong Toh
Summary: This study validates the safety and efficacy of human mesenchymal stem cell (MSC) exosomes combined with hyaluronic acid (HA) for osteochondral repair in a clinically relevant micropig model. The results show that the combination treatment promotes functional cartilage and subchondral bone repair, with significantly improved morphological, histological, and biomechanical outcomes. No adverse response or major systemic alterations were observed, indicating the potential of this therapy for clinical applications.
AMERICAN JOURNAL OF SPORTS MEDICINE
(2022)
Article
Cell & Tissue Engineering
Jia Tong Loh, Bin Zhang, Joey Kay Hui Teo, Ruenn Chai Lai, Andre Boon Hwa Choo, Kong-Peng Lam, Sai Kiang Lim
Summary: This study identified a feed-forward loop between complements and neutrophils that contributes to the cytokine storm in severe SARS-CoV-2-infected patients. It was observed that the terminal complement activation complex C5b-9 directly triggers neutrophil extracellular trap (NET) release and interleukin (IL)-17 production by neutrophils. Mesenchymal stem cell (MSC) exosomes were found to inhibit this loop by suppressing complement activation through exosomal CD59, suggesting their potential role in alleviating immune dysregulation and inflammation in acute respiratory failure.
Review
Cardiac & Cardiovascular Systems
Sean M. Davidson, Chantal M. Boulanger, Elena Aikawa, Lina Badimon, Lucio Barile, Christoph J. Binder, Alain Brisson, Edit Buzas, Costanza Emanueli, Felix Jansen, Miroslava Katsur, Romaric Lacroix, Sai Kiang Lim, Nigel Mackman, Manuel Mayr, Philippe Menasche, Rienk Nieuwland, Susmita Sahoo, Kaloyan Takov, Thomas Thum, Pieter Vader, Marca H. M. Wauben, Kenneth Witwer, Joost P. G. Sluijter
Summary: This article provides an overview of the techniques and technologies available for the separation and characterization of EVs from different sources. It discusses methods for determining the protein, RNA, and lipid content of EVs. The guidance provided in this document is important for investigating the role of EVs in cardiovascular diseases and highlights key methodological issues to consider.
CARDIOVASCULAR RESEARCH
(2023)
Review
Cell Biology
Marta Garcia-Contreras, Avnesh S. Thakor
Summary: Alzheimer's disease is a fatal neurodegenerative disorder that requires early diagnosis and disease monitoring. Extracellular vesicles, as a novel class of biomarkers and biological therapeutics, have great potential. This review summarizes and discusses the latest findings in this field.
NEURAL REGENERATION RESEARCH
(2023)
Article
Cell & Tissue Engineering
Ruenn Chai Lai, Thong Teck Tan, Wei Kian Sim, Bin Zhang, Sai Kiang Lim
Summary: The most clinically trialed cells, mesenchymal stromal cells (MSCs), exert their therapeutic activity through paracrine secretions, including exosomes. In this study, MSC exosomes were produced using a monoclonal cell line that does not form tumors or exhibit anchorage-independent growth. Topical application of MSC exosomes in a mouse model of psoriasis reduced inflammatory markers in the skin. The mechanism of action involves the permeation of exosomes through the psoriatic skin to inhibit the complement complex and IL-17 secretion.
Article
Biochemistry & Molecular Biology
Hon Shing Ong, Andri K. Riau, Gary Hin-Fai Yam, Nur Zahirah Binte M. Yusoff, Evelina J. Y. Han, Tze-Wei Goh, Ruenn Chai Lai, Sai Kiang Lim, Jodhbir S. Mehta
Summary: This study investigated the therapeutic effects of MSC-derived exosomes (MSC-exo) on corneal injury in a rat model. The results showed that MSC-exo treatment promoted wound closure, reduced corneal haze, attenuated vascularization and fibrosis, and modulated the immune response towards a regenerative and anti-inflammatory phenotype. These findings suggest that topical application of MSC-exo could be a potential therapeutic approach for corneal scarring.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Bin Zhang, Biyan Zhang, Ruenn Chai Lai, Wei Kian Sim, Kong Peng Lam, Sai Kiang Lim
Summary: Mesenchymal stem/stromal cell small extracellular vesicles (MSC-sEVs) have shown promise in treating various human diseases in animal models. However, the potential for contraindication in fibrotic diseases due to their ability to induce pro-fibrotic M2 macrophage polarization is an important consideration. Despite this, MSC-sEVs were found to be effective in reducing liver fibrosis in a mouse model of non-alcoholic steatohepatitis (NASH).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Diego Grassi, Agata Idziak, Antony Lee, Ivo Calaresu, Jean-Baptiste Sibarita, Laurent Cognet, Laurent Groc
Summary: The extracellular space (ECS) and its constituents have important functions in brain development, plasticity, circadian rhythm, and behavior, as well as brain diseases. However, exploring the nanoscale dimensions of the ECS in live tissue is challenging due to its complex geometry and small size. In this study, using single-nanoparticle tracking and super-resolution microscopy, the nanoscale dimensions of the ECS in the rodent hippocampus were mapped. The results show that these dimensions are heterogeneous between different areas of the hippocampus, and the dynamics and distribution of extracellular molecules are affected by these differences.
Article
Pharmacology & Pharmacy
Kristeen Ye Wen Teo, Shipin Zhang, Jia Tong Loh, Ruenn Chai Lai, Hwee Weng Dennis Hey, Kong-Peng Lam, Sai Kiang Lim, Wei Seong Toh
Summary: MSC exosomes promote the polarization of M2-like macrophages through activation of the toll-like receptor signaling pathway and CD73-mediated adenosine production. The production of adenosine activates AKT/ERK-dependent signaling pathways via binding to adenosine receptors A(2A) and A(2B). These findings highlight the critical role of CD73 in mediating M2-like macrophage polarization by MSC exosomes, and have implications for predicting the immunomodulatory potency of MSC exosome preparations.
Article
Biochemistry & Molecular Biology
Yael Macarena Cuasolo, Sebastian Dupraz, Nicolas Unsain, Mariano Bisbal, Gonzalo Quassollo, Mauricio R. Galiano, Diego Grassi, Santiago Quiroga, Lucas Javier Sosa
Summary: The development of mammalian neocortex requires migration of neurons from the ventricular zone to the cortical plate. This migration is regulated by small GTPase Rab21, which influences cell migration by controlling the trafficking of endocytic vesicles containing adhesion molecules. In this study, it is demonstrated that Rab21 plays a critical role in cortical neuronal differentiation and migration by regulating amyloid precursor protein levels on the neuronal cell surface. These findings improve our understanding of cerebral cortex development and cortical development disorders associated with Rab21 signaling effectors malfunction.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Bin Zhang, Ruenn Chai Lai, Wei Kian Sim, Sai Kiang Lim
Summary: The study suggests that mesenchymal stem/stromal cell small extracellular vesicles (MSC-sEVs) could be potential biologic disease-modifying antirheumatic drugs (DMARDs) for rheumatoid arthritis (RA). MSC-sEVs can reduce disease progression, disease severity, inflammation, and joint damage by increasing anti-inflammatory M2 macrophages and decreasing pro-inflammatory M1 macrophages.
Meeting Abstract
Cell & Tissue Engineering
Wei Seong Toh, Chee Weng Yong, Shang Jiunn Chuah, Raymond Wong, Asher Lim, Sai Kiang Lim
TISSUE ENGINEERING PART A
(2022)
Meeting Abstract
Cell & Tissue Engineering
Wei Seong Toh, Shipin Zhang, Keng Lin Wong, Sai Kiang Lim, James Hoi Po Hui
TISSUE ENGINEERING PART A
(2022)
