Comparative proteomic profiling of Small Extracellular vesicles derived from iPSCs and tissue specific mesenchymal stem cells

Gupta, Suchi; Krishnakumar, V.; Soni, Naina; Rao, Ercole; Banerjee, Arup; Mohanty, Sujata

doi:10.1016/j.yexcr.2022.113354

Cited by 15 publications

(10 citation statements)

References 56 publications

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“…This is particularly interesting in a diabetic wound healing model specifically, given the role of IGF1 in insulin regulation 49 . This result may also be supported by a recent study that profiled cargos within iPSC EVs, showing that many of these cargos are involved with modulating metabolism and aging, which IGF1 is also involved in 50, 51 .…”

Section: Discussionsupporting

confidence: 60%

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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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

Section: Discussionsupporting

confidence: 60%

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

View full text Add to dashboard Cite

show abstract

“…[45] This result may also be supported by a recent study that profiled cargos within iPSC EVs, showing that many of these cargos are involved with modulating metabolism and aging, which IGF1 is also involved in. [46,47] Given evidence that macrophage phenotypes are also related to cellular metabolism, it is possible that iPSC EVs may impart the observed "M2" transition through a similar pathway. [48][49][50] However, further studies into the mechanism behind these antiinflammatory phenomena are needed.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

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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“…In hPSCs, EXO content was more focused on development, metabolism, and anti-aging properties, and in hMSCs, it was related to immune regulation. Another study in 2022 also indicated that hMSC-EV content is strongly related to immune regulation while hPSC-EV content does not present many of the proteins related to this function[ 76 ]. Actually, 79 proteins were found to be shared between hMSC- and hPSC-EVs, yet the main biological processes related to them were DNA regulation, signal transduction and cell communication[ 76 ].…”

Section: Hpsc-evsmentioning

confidence: 99%

“…Another study in 2022 also indicated that hMSC-EV content is strongly related to immune regulation while hPSC-EV content does not present many of the proteins related to this function[ 76 ]. Actually, 79 proteins were found to be shared between hMSC- and hPSC-EVs, yet the main biological processes related to them were DNA regulation, signal transduction and cell communication[ 76 ]. Liu et al [ 59 ] also compared the protein content of hiPSC-EVs and hMSC-EVs and described more than 1100 proteins shared between the different EVs, allowing to identify proteins that could be responsible for the anti-senescent effect observed in the study.…”

Section: Hpsc-evsmentioning

confidence: 99%

Human pluripotent stem cell-derived extracellular vesicles: From now to the future

Matos¹,

Stimamiglio²,

Correa³

et al. 2023

World J Stem Cells

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Extracellular vesicles (EVs) are nanometric particles that enclose cell-derived bioactive molecules in a lipid bilayer and serve as intercellular communication tools. Accordingly, in various biological contexts, EVs are reported to engage in immune modulation, senescence, and cell proliferation and differentiation. Therefore, EVs could be key elements for potential off-the-shelf cell-free therapy. Little has been studied regarding EVs derived from human pluripotent stem cells (hPSC-EVs), even though hPSCs offer good opportunities for induction of tissue regeneration and unlimited proliferative ability. In this review article, we provide an overview of studies using hPSC-EVs, focusing on identifying the conditions in which the cells are cultivated for the isolation of EVs, how they are characterized, and applications already demonstrated. The topics reported in this article highlight the incipient status of the studies in the field and the significance of hPSC-EVs’ prospective applications as PSC-derived cell-free therapy products.

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Comparative proteomic profiling of Small Extracellular vesicles derived from iPSCs and tissue specific mesenchymal stem cells

Cited by 15 publications

References 56 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

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

Human pluripotent stem cell-derived extracellular vesicles: From now to the future

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