Stem Cell Extracellular Vesicles: Extended Messages of Regeneration

Riazifar, Milad; Pone, Egest J.; Lötvall, Jan; Zhao, Weian

doi:10.1146/annurev-pharmtox-061616-030146

Cited by 247 publications

(245 citation statements)

References 213 publications

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“…The clinical use of MSC EVs requires a scale-up of the EV production, good manufacturing practice (GMP) protocols and numerous other regulatory considerations [34]. One of the safety considerations is the use of animal free/bovine EV-free media.…”

Section: Discussionmentioning

confidence: 99%

Efficient ultrafiltration‐based protocol to deplete extracellular vesicles from fetal bovine serum

Kornilov

Puhka

Mannerström

et al. 2018

J of Extracellular Vesicle

147

125

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Fetal bovine serum (FBS) is the most commonly used supplement in studies involving cell-culture experiments. However, FBS contains large numbers of bovine extracellular vesicles (EVs), which hamper the analyses of secreted EVs from the cell type of preference and, thus, also the downstream analyses. Therefore, a prior elimination of EVs from FBS is crucial. However, the current methods of EV depletion by ultracentrifugation are cumbersome and the commercial alternatives expensive. In this study, our aim was to develop a protocol to completely deplete EVs from FBS, which may have wide applicability in cell-culture applications. We investigated different EV-depleted FBS prepared by our novel ultrafiltration-based protocol, by conventionally used overnight ultracentrifugation, or commercially available depleted FBS, and compared them with regular FBS. All sera were characterized by nanoparticle tracking analysis, electron microscopy, Western blotting and RNA quantification. Next, adipose-tissue mesenchymal stem cells (AT-MSCs) and cancer cells were grown in the media supplemented with the three different EV-depleted FBS and compared with cells grown in regular FBS media to assess the effects on cell proliferation, stress, differentiation and EV production. The novel ultrafiltration-based protocol depleted EVs from FBS clearly more efficiently than ultracentrifugation and commercial methods. Cell proliferation, stress, differentiation and EV production of AT-MSCs and cancer cell lines were similarly maintained in all three EV-depleted FBS media up to 96 h. In summary, our ultrafiltration protocol efficiently depletes EVs, is easy to use and maintains cell growth and metabolism. Since the method is also cost-effective and easy to standardize, it could be used in a wide range of cell-culture applications helping to increase comparability of EV research results between laboratories.

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Section: Discussionmentioning

confidence: 99%

Efficient ultrafiltration‐based protocol to deplete extracellular vesicles from fetal bovine serum

Kornilov

Puhka

Mannerström

et al. 2018

J of Extracellular Vesicle

147

125

View full text Add to dashboard Cite

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“…Robustness and reproducibility of many of these proposed approaches, however, await support by solid preclinical and early clinical data [8]. While few companies have well developed and focused portfolios (e.g., ReNeuron, Capricor, Codiak), others have just passed the phase of establishment.…”

Section: Introductionmentioning

confidence: 99%

Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use

Gimona

Pachler

Laner-Plamberger

et al. 2017

IJMS

242

192

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Extracellular vesicles (EVs) derived from stem and progenitor cells may have therapeutic effects comparable to their parental cells and are considered promising agents for the treatment of a variety of diseases. To this end, strategies must be designed to successfully translate EV research and to develop safe and efficacious therapies, whilst taking into account the applicable regulations. Here, we discuss the requirements for manufacturing, safety, and efficacy testing of EVs along their path from the laboratory to the patient. Development of EV-therapeutics is influenced by the source cell types and the target diseases. In this article, we express our view based on our experience in manufacturing biological therapeutics for routine use or clinical testing, and focus on strategies for advancing mesenchymal stromal cell (MSC)-derived EV-based therapies. We also discuss the rationale for testing MSC-EVs in selected diseases with an unmet clinical need such as critical size bone defects, epidermolysis bullosa and spinal cord injury. While the scientific community, pharmaceutical companies and clinicians are at the point of entering into clinical trials for testing the therapeutic potential of various EV-based products, the identification of the mode of action underlying the suggested potency in each therapeutic approach remains a major challenge to the translational path.

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“…EVs are easy to manufacture and to bioengineer with multiple factors while maintaining their biostability. Furthermore, since they are small and acellular, they might avoid entrapment in different organs, for example, the lungs and may potentially also be able to cross biological barriers …”

Section: Preclinical Studies and Clinical Trials In Fetal Therapymentioning

confidence: 99%

Prenatal stem cell therapy for inherited diseases: Past, present, and future treatment strategies

Ekblad‐Nordberg

Walther‐Jallow

Westgren

2019

Stem Cells Translational Medicine

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Imagine the profits in quality of life that can be made by treating inherited diseases early in life, maybe even before birth! Immense cost savings can also be made by treating diseases promptly. Hence, prenatal stem cell therapy holds great promise for developing new and early-stage treatment strategies for several diseases. Successful prenatal stem cell therapy would represent a major step forward in the management of patients with hematological, metabolic, or immunological disorders. However, treatment before birth has several limitations, including ethical issues. In this review, we summarize the past, the present, and the future of prenatal stem cell therapy, which includes an overview of different stem cell types, preclinical studies, and clinical attempts treating various diseases. We also discuss the current challenges and future strategies for prenatal stem cell therapy and also new approaches, which may lead to advancement in the management of patients with severe incurable diseases. K E Y W O R D Scell therapy, inherited diseases, prenatal, stem cell, treatment strategies

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Stem Cell Extracellular Vesicles: Extended Messages of Regeneration

Cited by 247 publications

References 213 publications

Efficient ultrafiltration‐based protocol to deplete extracellular vesicles from fetal bovine serum

Efficient ultrafiltration‐based protocol to deplete extracellular vesicles from fetal bovine serum

Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use

Prenatal stem cell therapy for inherited diseases: Past, present, and future treatment strategies

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