Potential of Exosomes as Cell-Free Therapy in Articular Cartilage Regeneration: A Review

Ng, Chiew Yong; Chai, Jia Ying; Foo, Jhi Biau; Yahaya, Nor Hamdan Mohamad; Yang, Ying; Ng, Min Hwei; Law, Jia Xian

doi:10.2147/ijn.s327059

Cited by 25 publications

(14 citation statements)

References 170 publications

(441 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…51 Exosomes are an important carrier for the intercellular exchange of information and effective substitutes for simulating the bioregulating functions of original cells. 52 The modulating potential of exosomes from various cells for the regenerative microenvironment has been widely explored in the field of intervertebral disc rebuilding.…”

Section: Discussionmentioning

confidence: 99%

Exosomes from M2c macrophages alleviate intervertebral disc degeneration by promoting synthesis of the extracellular matrix via MiR‐124/CILP/TGF‐β

Liu

Xue²,

Han³

et al. 2023

Bioengineering & Transla Med

View full text Add to dashboard Cite

Immuno‐inflammation is highly associated with anabolic and catabolic dysregulation of the extracellular matrix (ECM) in the nucleus pulposus (NP), which dramatically propels intervertebral disc degeneration (IVDD). With the characteristics of tissue remodeling and regeneration, M2c macrophages have attracted great attention in research on immune modulation that rebuilds degenerated tissues. Therefore, we first demonstrated the facilitating effects of M2c macrophages on ECM anabolism of the NP in vitro. We subsequently found that exosomes from M2c macrophages (M2c‐Exoss) mediated their metabolic rebalancing effects on the ECM. To determine whether M2c‐Exoss served as positive agents protecting the ECM in IVDD, we constructed an M2c‐Exos‐loaded hyaluronic acid hydrogel (M2c‐Exos@HA hydrogel) and implanted it into the degenerated caudal disc of rats. The results of MRI and histological staining indicated that the M2c‐Exos@HA hydrogel alleviated IVDD in vivo in the long term. To elucidate the underlying molecular mechanism, we performed 4D label‐free proteomics to screen dysregulated proteins in NPs treated with M2c‐Exoss. Cartilage intermediate layer protein (CILP) was the key protein responsible for the rebalancing effects of M2c‐Exoss on ECM metabolism in the NP. With prediction and verification using luciferase assays and rescue experiments, miR‐124‐3p was identified as the upstream regulator in M2c‐Exoss that regulated CILP and consequently enhanced the activity of the TGF‐β/smad3 pathway. In conclusion, we demonstrated ameliorating effects of M2c‐Exoss on the imbalance of ECM metabolism in IVDD via the miR‐124/CILP/TGF‐β regulatory axis, which provides a promising theoretical basis for the application of M2c macrophages and their exosomes in the treatment of IVDD.

show abstract

Section: Discussionmentioning

confidence: 99%

Exosomes from M2c macrophages alleviate intervertebral disc degeneration by promoting synthesis of the extracellular matrix via MiR‐124/CILP/TGF‐β

Liu

Xue²,

Han³

et al. 2023

Bioengineering & Transla Med

View full text Add to dashboard Cite

show abstract

“…Undesired RNAs (e.g., retroviral genomes) or proteins unintentionally incorporated in exosomes, as well as off-target delivery, are also issues that need to be carefully considered. In addition, although encapsulating exosomes within a scaffold is a feasible option to achieve controlled release of exosomes and reduce the number of injections needed [161], material pharmacokinetics and possible toxicity should be carefully evaluated. Due to a lack of effective methods to separate exosomes from the other two kinds of EVs, it remains a challenge to explicitly elucidate the functions and physiochemical properties of exosomes.…”

Section: Discussionmentioning

confidence: 99%

Exosomes in the Pathogenesis, Progression, and Treatment of Osteoarthritis

Fan

2022

Bioengineering

View full text Add to dashboard Cite

Osteoarthritis (OA) is a prevalent and debilitating age-related joint disease characterized by articular cartilage degeneration, synovial membrane inflammation, osteophyte formation, as well as subchondral bone sclerosis. OA drugs at present are mainly palliative and do not halt or reverse disease progression. Currently, no disease-modifying OA drugs (DMOADs) are available and total joint arthroplasty remains a last resort. Therefore, there is an urgent need for the development of efficacious treatments for OA management. Among all novel pharmaco-therapeutical options, exosome-based therapeutic strategies are highly promising. Exosome cargoes, which include proteins, lipids, cytokines, and various RNA subtypes, are potentially capable of regulating intercellular communications and gene expression in target cells and tissues involved in OA development. With extensive research in recent years, exosomes in OA studies are no longer limited to classic, mesenchymal stem cell (MSC)-derived vesicles. New origins, structures, and functions of exosomes are constantly being discovered and investigated. This review systematically summarizes the non-classic origins, biosynthesis, and extraction of exosomes, describes modification and delivery techniques, explores their role in OA pathogenesis and progression, and discusses their therapeutic potential and hurdles to overcome in OA treatment.

show abstract

“…Furthermore, EVs have been considered delivery vehicles that could protect RNA molecules from degradation during the transportation process within the extracellular environment. 25 …”

Section: Biogenesis and Function Of Mirnasmentioning

confidence: 99%

The Application of Extracellular Vesicles Mediated miRNAs in Osteoarthritis: Current Knowledge and Perspective

Shang¹,

Yan²,

Yang³

et al. 2022

JIR

View full text Add to dashboard Cite

Osteoarthritis (OA) is a whole joint disease characterized by synovitis, cartilage destruction, and subchondral bone sclerosis and cyst. Despite decades’ study, effective treatment is rare for this chronic disease. Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptosis bodies, are nano-sized vesicles with a cargo containing biologically active agents, such as nucleic acids, lipids, and proteins. As a group of short non-coding RNAs, microRNAs (miRNAs) can be delivered by parental cells secreted EVs. Negatively regulate the target mRNAs at the posttranscriptional level and regulate gene expression in recipient cells without modifying gene sequence. Recently, most studies focused on the function of EVs mediated miRNAs in the pathophysiological process of OA. However, all kinds of EVs specific and OA specific factors might influence the administration of EVs-miRNAs, especially the precise quantitative management. As a result, the flourishing of current research about EVs in the laboratory might not promote the relevant clinical transformation in OA treatment. In this review, we reviewed the present application of EVs-miRNAs in the therapeutic of OA and further analyzed the potential factors that might influence its application. Further progress in the quantitative management of EVs-miRNAs would accelerate the clinical transformation of miRNAs enriched EVs in the OA field.

show abstract

Potential of Exosomes as Cell-Free Therapy in Articular Cartilage Regeneration: A Review

Cited by 25 publications

References 170 publications

Exosomes from M2c macrophages alleviate intervertebral disc degeneration by promoting synthesis of the extracellular matrix via MiR‐124/CILP/TGF‐β

Exosomes from M2c macrophages alleviate intervertebral disc degeneration by promoting synthesis of the extracellular matrix via MiR‐124/CILP/TGF‐β

Exosomes in the Pathogenesis, Progression, and Treatment of Osteoarthritis

The Application of Extracellular Vesicles Mediated miRNAs in Osteoarthritis: Current Knowledge and Perspective

Contact Info

Product

Resources

About