Assessment of anti-inflammatory bioactivity of extracellular vesicles is susceptible to error via media component contamination

Kronstadt, Stephanie M.; Heyningen, Lauren Hoorens Van; Aranda, Amaya; Jay, Steven M.

doi:10.1016/j.jcyt.2022.12.002

Cited by 5 publications

(3 citation statements)

References 64 publications

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“…Our group previously reported on media contaminants affecting the outcomes of anti‐inflammatory assays involving EVs. [ 29 ] To verify that the reductions in pro‐inflammatory cytokine secretion in this model were due to EVs and not media contaminants, the RAW264.7 pre‐treat assay was performed using mTESR Plus that had undergone the EV isolation process. We observed that the mTESR Plus depletion protocol was effective at removing contaminants that may skew anti‐inflammatory assay results; additionally, we saw that upon culture with iPSC EVs, the anti‐inflammatory effect was restored (Figure S5A, Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

Induced Pluripotent Stem Cell‐Derived Extracellular Vesicles Promote Wound Repair in a Diabetic Mouse Model via an Anti‐Inflammatory Immunomodulatory Mechanism

Levy

Abadchi

Shababi

et al. 2023

Adv Healthcare Materials

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Extracellular vesicles (EVs) derived from mesenchymal stem/stromal cells (MSCs) have recently been explored in clinical trials for treatment of diseases with complex pathophysiologies. However, production of MSC EVs is currently hampered by donor‐specific characteristics and limited ex vivo expansion capabilities before decreased potency, thus restricting their potential as a scalable and reproducible therapeutic. Induced pluripotent stem cells (iPSCs) represent a self‐renewing source for obtaining differentiated iPSC‐derived MSCs (iMSCs), circumventing both scalability and donor variability concerns for therapeutic EV production. Thus, it is initially sought to evaluate the therapeutic potential of iMSC EVs. Interestingly, while utilizing undifferentiated iPSC EVs as a control, it is found that their vascularization bioactivity is similar and their anti‐inflammatory bioactivity is superior to donor‐matched iMSC EVs in cell‐based assays. To supplement this initial in vitro bioactivity screen, a diabetic wound healing mouse model where both the pro‐vascularization and anti‐inflammatory activity of these EVs would be beneficial is employed. In this in vivo model, iPSC EVs more effectively mediate inflammation resolution within the wound bed. Combined with the lack of additional differentiation steps required for iMSC generation, these results support the use of undifferentiated iPSCs as a source for therapeutic EV production with respect to both scalability and efficacy.

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Section: Resultsmentioning

confidence: 99%

Induced Pluripotent Stem Cell‐Derived Extracellular Vesicles Promote Wound Repair in a Diabetic Mouse Model via an Anti‐Inflammatory Immunomodulatory Mechanism

Levy

Abadchi

Shababi

et al. 2023

Adv Healthcare Materials

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“…However, the downregulation of relative mRNA expression of Rank by M0-CM is inconsistent with M0-EVs, which may be attributed to the presence of other active components in the CM, including maternal leukocytes, growth factors, and cytokines, excluding EVs. 20 In comparison to M2-EVs, EVs derived from M2 macrophages following a 48-h induction with IL-4 did not demonstrate superior proficiency in the phenotypic characteristics of OCPs, nor did the macrophages that secreted these EVs exhibit enhanced cell viability ( Figures 2 I, 2J, and S2 D). Therefore, it is plausible that the EVs selected within the initial 48-h period may possess superior capabilities.…”

Section: Resultsmentioning

confidence: 89%

M2 macrophages secrete glutamate-containing extracellular vesicles to alleviate osteoporosis by reshaping osteoclast precursor fate

Huang,

Lan,

Shen

et al. 2024

Molecular Therapy

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“…Additionally, utilizing a stimulated human THP-B A 1 assay, both iPSC EVs and iMSC EVs induced a robust decrease in TNF-secretion as assessed by ELISA (Figure 5B). Our group previously reported on media contaminants affecting the outcomes of antiinflammatory assays involving EVs 33 . To verify that the reductions in pro-inflammatory cytokine secretion in this model were due to EVs and not media contaminants, the RAW264.7 pre-treat assay was performed using mTESR Plus that had undergone the EV isolation process.…”

Section: A B Cmentioning

confidence: 99%

Induced pluripotent stem cell-derived extracellular vesicles promote wound repair in a diabetic mouse model via an anti-inflammatory immunomodulatory mechanism

Levy

Abadchi

Shababi

et al. 2023

Preprint

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View full text Add to dashboard Cite

Extracellular vesicles (EVs) derived from mesenchymal stem/stromal cells (MSCs) have recently been widely explored in clinical trials for treatment of diseases with complex pathophysiology. However, production of MSC EVs is currently hampered by donor-specific characteristics and limited ex vivo expansion capabilities before decreased potency, thus restricting their potential as a scalable and reproducible therapeutic. Induced pluripotent stem cells (iPSCs) represent a self-renewing source for obtaining differentiated iPSC-derived MSCs (iMSCs), circumventing both scalability and donor variability concerns for therapeutic EV production. Thus, we initially sought to evaluate the therapeutic potential of iMSC EVs. Interestingly, while utilizing undifferentiated iPSC EVs as a control, we found that their vascularization bioactivity was similar and their anti-inflammatory bioactivity was superior to donor-matched iMSC EVs in cell-based assays. To supplement this initial in vitro bioactivity screen, we employed a diabetic wound healing mouse model where both the pro-vascularization and anti-inflammatory activity of these EVs would be beneficial. In this in vivo model, iPSC EVs more effectively mediated inflammation resolution within the wound bed. Combined with the lack of additional differentiation steps required for iMSC generation, these results support the use of undifferentiated iPSCs as a source for therapeutic EV production with respect to both scalability and efficacy.

show abstract

Assessment of anti-inflammatory bioactivity of extracellular vesicles is susceptible to error via media component contamination

Cited by 5 publications

References 64 publications

Induced Pluripotent Stem Cell‐Derived Extracellular Vesicles Promote Wound Repair in a Diabetic Mouse Model via an Anti‐Inflammatory Immunomodulatory Mechanism

Induced Pluripotent Stem Cell‐Derived Extracellular Vesicles Promote Wound Repair in a Diabetic Mouse Model via an Anti‐Inflammatory Immunomodulatory Mechanism

M2 macrophages secrete glutamate-containing extracellular vesicles to alleviate osteoporosis by reshaping osteoclast precursor fate

Induced pluripotent stem cell-derived extracellular vesicles promote wound repair in a diabetic mouse model via an anti-inflammatory immunomodulatory mechanism

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