Extracellular Vesicle Heterogeneity and Its Impact for Regenerative Medicine Applications

Wakker, Simonides Immanuel van de; Meijers, Fleur Michelle; Sluijter, Joost P.G.; Vader, Pieter

doi:10.1124/pharmrev.123.000841

Cited by 23 publications

(14 citation statements)

References 224 publications

(306 reference statements)

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“…To delve deeper into this, employing affinity separation methods to isolate sEVs with specific surface markers could offer a more comprehensive understanding. Nevertheless, subdividing the isolated sEV subpopulations might reduce the yield of recovered sEVs, consequently restricting subsequent functional characterization (van de Wakker et al., 2023). Our proteomic analysis also revealed that subpopulation P3 displayed partial overlapping proteomic content with P2, particularly regarding enrichment of matrix proteins and histones.…”

Section: Discussionmentioning

confidence: 99%

Size matters: Functional differences of small extracellular vesicle subpopulations in cardiac repair responses

van de Wakker,

Bauzá‐Martinez,

Ríos Arceo

et al. 2024

J of Extracellular Vesicle

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Cardiac progenitor cell (CPC)‐derived small extracellular vesicles (sEVs) exhibit great potential to stimulate cardiac repair. However, the multifaceted nature of sEV heterogeneity presents a challenge in understanding the distinct mechanisms underlying their regenerative abilities. Here, a dual‐step multimodal flowthrough and size‐exclusion chromatography method was applied to isolate and separate CPC‐derived sEV subpopulations to study the functional differences related to cardiac repair responses. Three distinct sEV subpopulations were identified with unique protein profiles. Functional cell assays for cardiac repair‐related processes demonstrated that the middle‐sized and smallest‐sized sEV subpopulations exhibited the highest pro‐angiogenic and anti‐fibrotic activities. Proteasome activity was uniquely seen in the smallest‐sized subpopulation. The largest‐sized subpopulation showed no effect in any of the functional assays. This research uncovers the existence of sEV subpopulations, each characterized by a distinct composition and biological function. Enhancing our understanding of sEV heterogeneity will provide valuable insights into sEV mechanisms of action, ultimately accelerating the translation of sEV therapeutics.

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Section: Discussionmentioning

confidence: 99%

Size matters: Functional differences of small extracellular vesicle subpopulations in cardiac repair responses

van de Wakker,

Bauzá‐Martinez,

Ríos Arceo

et al. 2024

J of Extracellular Vesicle

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“…Recent studies have indicated that small bilayer membrane vesicles, generally named as extracellular vesicles (EVs), or exosomes secreted by, for instance MSCs, can provide a novel avenue for tissue repair and the treatment of various diseases [ 146 ]. Extracellular vesicles are secreted by almost every type of cell, and they can carry various types of contents, such as proteins, lipids and non-coding/coding nucleic acids, to their target cells through cell-to-cell communications.…”

Section: Low Oxygen Effects On Chondrocytes and Chondrogenic Phenotypementioning

confidence: 99%

Regulation of Oxygen Tension as a Strategy to Control Chondrocytic Phenotype for Cartilage Tissue Engineering and Regeneration

Lammi,

2024

Bioengineering

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Cartilage defects and osteoarthritis are health problems which are major burdens on health care systems globally, especially in aging populations. Cartilage is a vulnerable tissue, which generally faces a progressive degenerative process when injured. This makes it the 11th most common cause of global disability. Conservative methods are used to treat the initial phases of the illness, while orthopedic management is the method used for more progressed phases. These include, for instance, arthroscopic shaving, microfracturing and mosaicplasty, and joint replacement as the final treatment. Cell-based implantation methods have also been developed. Despite reports of successful treatments, they often suffer from the non-optimal nature of chondrocyte phenotype in the repair tissue. Thus, improved strategies to control the phenotype of the regenerating cells are needed. Avascular tissue cartilage relies on diffusion for nutrients acquisition and the removal of metabolic waste products. A low oxygen content is also present in cartilage, and the chondrocytes are, in fact, well adapted to it. Therefore, this raises an idea that the regulation of oxygen tension could be a strategy to control the chondrocyte phenotype expression, important in cartilage tissue for regenerative purposes. This narrative review discusses the aspects related to oxygen tension in the metabolism and regulation of articular and growth plate chondrocytes and progenitor cell phenotypes, and the role of some microenvironmental factors as regulators of chondrocytes.

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“…EVs are expected to have great potential as a cell-free therapy to replace cell therapies. Stem cell-derived EVs are one of the major applications that have been investigated extensively as a drug-delivery platform in cancer therapy and tissue regeneration. ,, Stem cell-derived EVs have important benefits in various diseases due to their homing effects (for target tissues and organs) and their ability to transmit signal substances (such as growth factors, cytokines, and nucleic acids) . In particular, stem cell-derived EVs have demonstrated enhanced targeting efficiency along with tumor-regulating features and regulation of tumor progression.…”

Section: Types Of Stem Cellsmentioning

confidence: 99%

Stem Cell-Derived Extracellular Vesicles for Cancer Therapy and Tissue Engineering Applications

Lee,

et al. 2023

Mol. Pharmaceutics

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Recently, stem cells and their secretomes have attracted great attention in biomedical applications, particularly extracellular vesicles (EVs). EVs are secretomes of cells for cell-tocell communication. They play a role as intercellular messengers as they carry proteins, nucleic acids, lipids, and therapeutic agents. They have also been utilized as drug-delivery vehicles due to their biocompatibility, low immunogenicity, stability, targetability, and engineerable properties. The therapeutic potential of EVs can be further enhanced by surface engineering and modification using functional molecules such as aptamers, peptides, and antibodies. As a consequence, EVs hold great promise as effective delivery vehicles for enhancing treatment efficacy while avoiding side effects. Among various cell types that secrete EVs, stem cells are ideal sources of EVs because stem cells have unique properties such as self-renewal and regenerative potential for transplantation into damaged tissues that can facilitate their regeneration. However, challenges such as immune rejection and ethical considerations remain significant hurdles. Stem cell-derived EVs have been extensively explored as a cell-free approach that bypasses many challenges associated with cell-based therapy in cancer therapy and tissue regeneration. In this review, we summarize and discuss the current knowledge of various types of stem cells as a source of EVs, their engineering, and applications of EVs, focusing on cancer therapy and tissue engineering.

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Extracellular Vesicle Heterogeneity and Its Impact for Regenerative Medicine Applications

Cited by 23 publications

References 224 publications

Size matters: Functional differences of small extracellular vesicle subpopulations in cardiac repair responses

Size matters: Functional differences of small extracellular vesicle subpopulations in cardiac repair responses

Regulation of Oxygen Tension as a Strategy to Control Chondrocytic Phenotype for Cartilage Tissue Engineering and Regeneration

Stem Cell-Derived Extracellular Vesicles for Cancer Therapy and Tissue Engineering Applications

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