Mesenchymal Stem Cell-derived Extracellular Vesicles: Toward Cell-free Therapeutic Applications

Rani, Sweta; Ryan, Aideen E.; Griffin, Matthew D.; Ritter, Thomas

doi:10.1038/mt.2015.44

Cited by 967 publications

(865 citation statements)

References 153 publications

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“…MSC-derived exosomes (MSC-exosomes) have been used as a treatment for diseases and disorders of many systems such as the cardiovascular, neurological, musculoskeletal and immune systems [5,6,8,31]. Rats with traumatic brain injury exhibited significant functional recovery, increased neurite remodelling, angiogenesis and neurogenesis after treatment with exosomes [32].…”

Section: Msc-derived Exosomesmentioning

confidence: 99%

Engineering mesenchymal stem cells to improve their exosome efficacy and yield for cell‐free therapy

Phan

Kumar

Hao

et al. 2018

J of Extracellular Vesicle

239

197

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Through traditional medicine, there were diseases and disorders that previously remained untreated or were simply thought to be incurable. Since the discovery of mesenchymal stem cells (MSCs), there has been a flurry of research to develop MSC-based therapy for diseases and disorders. It is now well-known that MSCs do not typically engraft after transplantation and exhibit their therapeutic effect via a paracrine mechanism. In addition to secretory proteins, MSCs also produce extracellular vesicles (EVs), membrane-bound nanovesicles containing proteins, DNA and RNA. The secreted vesicles then interact with target cells and deliver their contents, imparting their ultimate therapeutic effect. Unlike the widely studied cancer cells, the yield of MSC-exosomes is a limiting factor for large-scale production for cell-free therapies. Here we summarise potential approaches to increase the yield of such vesicles while maintaining or enhancing their efficacy by engineering the extracellular environment and intracellular components of MSCs.

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Section: Msc-derived Exosomesmentioning

confidence: 99%

Engineering mesenchymal stem cells to improve their exosome efficacy and yield for cell‐free therapy

Phan

Kumar

Hao

et al. 2018

J of Extracellular Vesicle

239

197

View full text Add to dashboard Cite

show abstract

“…Small lipophilic molecules, such as antioxidants, curcumin, and anticancer agents, can be passively loaded into EVs or EVMs by simple incubation 52, 93, 94. Drugs, including curcumin, show advanced stability and bioavailability when encapsulated compared to free‐state drugs and have been successfully used in preclinical research 95.…”

Section: Modular Design Of the Lipid Bilayermentioning

confidence: 99%

Modularized Extracellular Vesicles: The Dawn of Prospective Personalized and Precision Medicine

2018

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Extracellular vesicles (EVs) are ubiquitous nanosized membrane vesicles consisting of a lipid bilayer enclosing proteins and nucleic acids, which are active in intercellular communications. EVs are increasingly seen as a vital component of many biological functions that were once considered to require the direct participation of stem cells. Consequently, transplantation of EVs is gradually becoming considered an alternative to stem cell transplantation due to their significant advantages, including their relatively low probability of neoplastic transformation and abnormal differentiation. However, as research has progressed, it is realized that EVs derived from native‐source cells may have various shortcomings, which can be corrected by modification and optimization. To date, attempts are made to modify or improve almost all the components of EVs, including the lipid bilayer, proteins, and nucleic acids, launching a new era of modularized EV therapy through the “modular design” of EV components. One high‐yield technique, generating EV mimetic nanovesicles, will help to make industrial production of modularized EVs a reality. These modularized EVs have highly customized “modular design” components related to biological function and targeted delivery and are proposed as a promising approach to achieve personalized and precision medicine.

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“…Mechanically derived MSC versus enzymatically isolated MSC have shown to have better differentiation potential, much larger secretome content, and a large difference in exosomes contents [14] [21] [22].…”

Section: Introductionmentioning

confidence: 99%

Non-Responding Knee Pain with Osteoarthritis, Meniscus and Ligament Tears Treated with Ultrasound Guided Autologous, Micro-Fragmented and Minimally Manipulated Adipose Tissue

Striano¹,

Battista²,

Bilboo³

2017

OJRM

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Background: Chronic knee pain from advanced osteoarthritis is often associated with tears in the fibro-cartilaginous meniscus and cruciate ligaments. The result is substantial pain and impairments and loss of daily function, thus limiting activity and quality of life. These often include pain, loss of range of 116 motion, inability to elevate the leg, pain increased with activity and gradual worsening over time. This represents a challenging clinical picture for which few non-surgical options are available. Most patients failing to respond to current methods of care are offered arthroplasty. Current therapies are focused on the relief of the symptoms but cannot repair the damage nor stop the degenerative process. Objective: This is a case study of the first subject in a continuing IRB to reach a 2.5 year end-point. Our intention was to investigate the potential benefits of using autologous, minimally manipulated fat graft in subjects with advanced osteoarthritis and meniscus pathology who had failed to obtain benefit from previous, standards of care. Study description: 73 YO male, end stage bone-on-bone right knee pain. First subject to reach the 2 1/2 year follow up after Lipogems® precision ultrasound guided injections. Material and Methods: Micro-fragmented fat was obtained using a minimal manipulation technology in a closed system, Lipogems®, without the addition of enzymes or other additives. Fat graft was injected under continuous ultrasound guidance. Results: VAS pain, KOOS function, range of motion and quadriceps strength improved after treatment. Conclusion: Autologous, micronized, and minimally manipulated adipose tissue resulted in significant improvement in pain, function and quality of life. No adverse events were reported.

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Mesenchymal Stem Cell-derived Extracellular Vesicles: Toward Cell-free Therapeutic Applications

Cited by 967 publications

References 153 publications

Engineering mesenchymal stem cells to improve their exosome efficacy and yield for cell‐free therapy

Engineering mesenchymal stem cells to improve their exosome efficacy and yield for cell‐free therapy

Modularized Extracellular Vesicles: The Dawn of Prospective Personalized and Precision Medicine

Non-Responding Knee Pain with Osteoarthritis, Meniscus and Ligament Tears Treated with Ultrasound Guided Autologous, Micro-Fragmented and Minimally Manipulated Adipose Tissue

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