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Cells
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Extracellular Vesicles: Potential Roles in Regenerative Medicine
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Extracellular Vesicles: Potential Roles in Regenerative Medicine

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Intracellular and Plasma Membranes".

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 13399

Special Issue Editor

Dr. Mehrnoosh Saghizadeh Ghiam

E-Mail Website
Guest Editor
Cedars-Sinai Medical Center, Biomedical Sciences, Los Angeles, CA 90048, USA
Interests: diabetic cornea; limbal stem cells; microRNA; extracellular vesicles/exosomes; wound healing; gene therapy; stem cell therapy; corneal epithelial regeneration; intercellular communication
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Extracellular vesicles (EVs) are nano-sized vesicles (50-1000 nm) comprising microvesicles, exosomes, ectosomes or shedding vesicles, which differ by their subcellular origin, type of release, and size. EVs are secreted by most cells and exert their effects by fusion to the target cells and transferring their cargo, which may include bioactive molecules such as proteins, lipids, mRNAs, and miRNAs. EVs are modulators of ECM turnover, angiogenesis, immune responses, stem cell survival, proliferation, and differentiation and have important roles in pathological conditions, such as cancer, inflammation, cardiovascular diseases, diabetes, as well as in wound healing.

Since EVs can deliver to specific target cell their contents that can also be modified by design and influence, the behavior of recipient cells suggests the potential of EVs as therapeutic delivery vehicles. Mesenchymal stem cell (MSC)-derived exosomes have protective activities in myocardial infarction, stroke, brain injury, and potential in enhancing cutaneous and corneal wound healing. Thus, EVs have a great potential for treatment of a variety of diseases due to their high stability and low immunogenicity. They can be loaded easily with drugs, miRNAs, or proteins of interest and then injected systemically or locally into the target tissues.

The goal of the present Special Issue is to provide evidence for the regenerative potential role of EVs in healthy and diseased conditions in different organs/tissues. Original studies, reviews, and technical reports in this field will be accepted.

Dr. Mehrnoosh Saghizadeh Ghiam
Guest Editor

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Keywords

  • extracellular vesicles/exosomes
  • microRNA
  • mesenchymal stem cells
  • adult stem cells
  • intercellular communication
  • tissue regeneration
  • cell targeting

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Published Papers (5 papers)

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Research

Jump to: Review

22 pages, 8401 KiB  
Article
MicroRNA and Protein Cargos of Human Limbal Epithelial Cell-Derived Exosomes and Their Regulatory Roles in Limbal Stromal Cells of Diabetic and Non-Diabetic Corneas
by Nagendra Verma, Drirh Khare, Adam J. Poe, Cynthia Amador, Sean Ghiam, Andrew Fealy, Shaghaiegh Ebrahimi, Odelia Shadrokh, Xue-Ying Song, Chintda Santiskulvong, Mitra Mastali, Sarah Parker, Aleksandr Stotland, Jennifer E. Van Eyk, Alexander V. Ljubimov and Mehrnoosh Saghizadeh
Cells 2023, 12(21), 2524; https://doi.org/10.3390/cells12212524 - 25 Oct 2023
Cited by 5 | Viewed by 1859
Abstract
Epithelial and stromal/mesenchymal limbal stem cells contribute to corneal homeostasis and cell renewal. Extracellular vesicles (EVs), including exosomes (Exos), can be paracrine mediators of intercellular communication. Previously, we described cargos and regulatory roles of limbal stromal cell (LSC)-derived Exos in non-diabetic (N) and [...] Read more.
Epithelial and stromal/mesenchymal limbal stem cells contribute to corneal homeostasis and cell renewal. Extracellular vesicles (EVs), including exosomes (Exos), can be paracrine mediators of intercellular communication. Previously, we described cargos and regulatory roles of limbal stromal cell (LSC)-derived Exos in non-diabetic (N) and diabetic (DM) limbal epithelial cells (LECs). Presently, we quantify the miRNA and proteome profiles of human LEC-derived Exos and their regulatory roles in N- and DM-LSC. We revealed some miRNA and protein differences in DM vs. N-LEC-derived Exos’ cargos, including proteins involved in Exo biogenesis and packaging that may affect Exo production and ultimately cellular crosstalk and corneal function. Treatment by N-Exos, but not by DM-Exos, enhanced wound healing in cultured N-LSCs and increased proliferation rates in N and DM LSCs vs. corresponding untreated (control) cells. N-Exos-treated LSCs reduced the keratocyte markers ALDH3A1 and lumican and increased the MSC markers CD73, CD90, and CD105 vs. control LSCs. These being opposite to the changes quantified in wounded LSCs. Overall, N-LEC Exos have a more pronounced effect on LSC wound healing, proliferation, and stem cell marker expression than DM-LEC Exos. This suggests that regulatory miRNA and protein cargo differences in DM- vs. N-LEC-derived Exos could contribute to the disease state. Full article
(This article belongs to the Special Issue Extracellular Vesicles: Potential Roles in Regenerative Medicine)
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12 pages, 3343 KiB  
Article
Engineered Nanovesicles from Fibroblasts Modulate Dermal Papillae Cells In Vitro and Promote Human Hair Follicle Growth Ex Vivo
by Ramya Lakshmi Rajendran, Prakash Gangadaran, Mi Hee Kwack, Ji Min Oh, Chae Moon Hong, Madhan Jeyaraman, Young Kwan Sung, Jaetae Lee and Byeong-Cheol Ahn
Cells 2022, 11(24), 4066; https://doi.org/10.3390/cells11244066 - 15 Dec 2022
Cited by 3 | Viewed by 1962
Abstract
Alopecia is a common medical condition affecting both sexes. Dermal papilla (DP) cells are the primary source of hair regeneration in alopecia patients. Therapeutic applications of extracellular vesicles (EVs) are restricted by low yields, high costs, and their time-consuming collection process. Thus, engineered [...] Read more.
Alopecia is a common medical condition affecting both sexes. Dermal papilla (DP) cells are the primary source of hair regeneration in alopecia patients. Therapeutic applications of extracellular vesicles (EVs) are restricted by low yields, high costs, and their time-consuming collection process. Thus, engineered nanovesicles (eNVs) have emerged as suitable therapeutic biomaterials in translational medicine. We isolated eNVs by the serial extrusion of fibroblasts (FBs) using polycarbonate membrane filters and serial and ultracentrifugation. We studied the internalization, proliferation, and migration of human DP cells in the presence and absence of FB-eNVs. The therapeutic potential of FB-eNVs was studied on ex vivo organ cultures of human hair follicles (HFs) from three human participants. FB-eNVs (2.5, 5, 7.5, and 10 µg/mL) significantly enhanced DP cell proliferation, with the maximum effect observed at 7.5 µg/mL. FB-eNVs (5 and 10 µg/mL) significantly enhanced the migration of DP cells at 36 h. Western blotting results suggested that FB-eNVs contain vascular endothelial growth factor (VEGF)-a. FB-eNV treatment increased the levels of PCNA, pAKT, pERK, and VEGF-receptor-2 (VEGFR2) in DP cells. Moreover, FB-eNVs increased the human HF shaft size in a short duration ex vivo. Altogether, FB-eNVs are promising therapeutic candidates for alopecia. Full article
(This article belongs to the Special Issue Extracellular Vesicles: Potential Roles in Regenerative Medicine)
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Review

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26 pages, 788 KiB  
Review
The Truth Is Out There: Biological Features and Clinical Indications of Extracellular Vesicles from Human Perinatal Stem Cells
by Eleonora Russo, Giusi Alberti, Simona Corrao, Cesar V. Borlongan, Vitale Miceli, Pier Giulio Conaldi, Francesca Di Gaudio and Giampiero La Rocca
Cells 2023, 12(19), 2347; https://doi.org/10.3390/cells12192347 - 25 Sep 2023
Cited by 6 | Viewed by 1432
Abstract
The potential of perinatal tissues to provide cellular populations to be used in different applications of regenerative medicine is well established. Recently, the efforts of researchers are being addressed regarding the evaluation of cell products (secreted molecules or extracellular vesicles, EVs) to be [...] Read more.
The potential of perinatal tissues to provide cellular populations to be used in different applications of regenerative medicine is well established. Recently, the efforts of researchers are being addressed regarding the evaluation of cell products (secreted molecules or extracellular vesicles, EVs) to be used as an alternative to cellular infusion. The data regarding the effective recapitulation of most perinatal cells’ properties by their secreted complement point in this direction. EVs secreted from perinatal cells exhibit key therapeutic effects such as tissue repair and regeneration, the suppression of inflammatory responses, immune system modulation, and a variety of other functions. Although the properties of EVs from perinatal derivatives and their significant potential for therapeutic success are amply recognized, several challenges still remain that need to be addressed. In the present review, we provide an up-to-date analysis of the most recent results in the field, which can be addressed in future research in order to overcome the challenges that are still present in the characterization and utilization of the secreted complement of perinatal cells and, in particular, mesenchymal stromal cells. Full article
(This article belongs to the Special Issue Extracellular Vesicles: Potential Roles in Regenerative Medicine)
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10 pages, 283 KiB  
Review
Mesenchymal Stem Cell-Derived Apoptotic Bodies: Biological Functions and Therapeutic Potential
by Huixue Tang, Huikun Luo, Zihan Zhang and Di Yang
Cells 2022, 11(23), 3879; https://doi.org/10.3390/cells11233879 - 1 Dec 2022
Cited by 19 | Viewed by 2896
Abstract
Mesenchymal stem cells (MSCs) are non-hematopoietic progenitor cells with self-renewal ability and multipotency of osteogenic, chondrogenic, and adipogenic differentiation. MSCs have appeared as a promising approach for tissue regeneration and immune therapies, which are attributable not only to their differentiation into the desired [...] Read more.
Mesenchymal stem cells (MSCs) are non-hematopoietic progenitor cells with self-renewal ability and multipotency of osteogenic, chondrogenic, and adipogenic differentiation. MSCs have appeared as a promising approach for tissue regeneration and immune therapies, which are attributable not only to their differentiation into the desired cells but also to their paracrine secretion. MSC-sourced secretome consists of soluble components including growth factors, chemokines, cytokines, and encapsulated extracellular vesicles (EVs). Apoptotic bodies (ABs) are large EVs (diameter 500𠀓2000 nm) harboring a variety of cellular components including microRNA, mRNA, DNA, protein, and lipids related to the characteristics of the originating cell, which are generated during apoptosis. The released ABs as well as the genetic information they carry are engulfed by target cells such as macrophages, dendritic cells, epithelial cells, and fibroblasts, and subsequently internalized and degraded in the lysosomes, suggesting their ability to facilitate intercellular communication. In this review, we discuss the current understanding of the biological functions and therapeutic potential of MSC-derived ABs, including immunomodulation, tissue regeneration, regulation of inflammatory response, and drug delivery system. Full article
(This article belongs to the Special Issue Extracellular Vesicles: Potential Roles in Regenerative Medicine)
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23 pages, 2738 KiB  
Review
The Emerging Role of Pericyte-Derived Extracellular Vesicles in Vascular and Neurological Health
by Kushal Sharma, Yunpei Zhang, Keshav Raj Paudel, Allan Kachelmeier, Philip M. Hansbro and Xiaorui Shi
Cells 2022, 11(19), 3108; https://doi.org/10.3390/cells11193108 - 2 Oct 2022
Cited by 21 | Viewed by 4466
Abstract
Pericytes (PCs), as a central component of the neurovascular unit, contribute to the regenerative potential of the central nervous system (CNS) and peripheral nervous system (PNS) by virtue of their role in blood flow regulation, angiogenesis, maintenance of the BBB, neurogenesis, and neuroprotection. [...] Read more.
Pericytes (PCs), as a central component of the neurovascular unit, contribute to the regenerative potential of the central nervous system (CNS) and peripheral nervous system (PNS) by virtue of their role in blood flow regulation, angiogenesis, maintenance of the BBB, neurogenesis, and neuroprotection. Emerging evidence indicates that PCs also have a role in mediating cell-to-cell communication through the secretion of extracellular vesicles (EVs). Extracellular vesicles are cell-derived, micro- to nano-sized vesicles that transport cell constituents such as proteins, nucleic acids, and lipids from a parent originating cell to a recipient cell. PC-derived EVs (PC-EVs) play a crucial homeostatic role in neurovascular disease, as they promote angiogenesis, maintain the integrity of the blood-tissue barrier, and provide neuroprotection. The cargo carried by PC-EVs includes growth factors such as endothelial growth factor (VEGF), connecting tissue growth factors (CTGFs), fibroblast growth factors, angiopoietin 1, and neurotrophic growth factors such as brain-derived neurotrophic growth factor (BDNF), neuron growth factor (NGF), and glial-derived neurotrophic factor (GDNF), as well as cytokines such as interleukin (IL)-6, IL-8, IL-10, and MCP-1. The PC-EVs also carry miRNA and circular RNA linked to neurovascular health and the progression of several vascular and neuronal diseases. Therapeutic strategies employing PC-EVs have potential in the treatment of vascular and neurodegenerative diseases. This review discusses current research on the characteristic features of EVs secreted by PCs and their role in neuronal and vascular health and disease. Full article
(This article belongs to the Special Issue Extracellular Vesicles: Potential Roles in Regenerative Medicine)
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