Heparin Can Augment Extracellular Vesicle Yield by Inhibiting Reuptake in Donor Cells During Cell Propagation
4 affiliations
- 1Paracelsus Medical University (PMU)
- 2Austrian Red Cross Research, OeRK
- 3Karolinska Institutet
- 4PMU
Abstract
Extracellular vesicles (EVs) mediate cell‐to‐cell communication in development, health and disease. Heparin is a common component in human induced pluripotent stem cell (hiPSC) media but its impact on hiPSC‐EVs beyond stabilizing growth factors is unknown. Published evidence indicates heparin dose‐dependent EV uptake inhibition in heterotypic target cells. We asked if heparin affects hiPSC‐EV yield, storage, phenotype, or function. We used large‐scale hiPSC‐EV propagation to obtain pro‐angiogenic hiPSC‐EVs in presence or absence of escalating heparin doses and determined EV quantity, identity and functionality. Heparin delayed hiPSC colony‐confluence without significantly affecting hiPSC viability, pluripotency markers and proliferation. Significantly elevated tetraspanin+/flotillin+ hiPSC‐EV number (mean 367±31 EVs/cell/24 h at 200 IU heparin/mL) enabled efficient purification of > 1011/mL functional EVs at superior particle/protein ratio > 1010/mg. Heparin dose‐dependently inhibited EV uptake in hiPSC and endothelial progenitors, comparable to 5 IU/mL flavobacterium heparinase, and increased EV recovery after storage in NaCl but not in cell‐conditioned media. EVs obtained from hiPSC at 1% O2 with 200 IU/mL heparin maintained superior angiogenesis similarly to control hiPSC‐EVs obtained without heparin. We conclude that heparin inhibits hiPSC‐EV reuptake and stabilizes NaCl‐cryopreserved EVs thus boosting EV recovery while maintaining pro‐angiogenic function. Heparin presence and dose should therefore be documented particularly in PSC media.
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BibTeX
@article{andrade2026heparin,
title = {{Heparin Can Augment Extracellular Vesicle Yield by Inhibiting Reuptake in Donor Cells During Cell Propagation}},
author = {André Cronemberger Andrade and Rodolphe Poupardin and Martin Wolf and Liliia Paniushkina and Karim Selmi and Deepika Kundully Suresh and Nicole Maeding and Heide‐Marie Binder and Janine Zwicklhuber and Sarah Hochmann and André Görgens and Samir El Andaloussi and Katharina Schallmoser and Dirk Strunk},
journal = {Journal of extracellular vesicles},
year = {2026},
month = oct,
doi = {10.1002/jev2.70382},
url = {https://europepmc.org/article/PMC/PMC13653646},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Heparin Can Augment Extracellular Vesicle Yield by Inhibiting Reuptake in Donor Cells During Cell Propagation
AU - André Cronemberger Andrade
AU - Rodolphe Poupardin
AU - Martin Wolf
AU - Liliia Paniushkina
AU - Karim Selmi
AU - Deepika Kundully Suresh
AU - Nicole Maeding
AU - Heide‐Marie Binder
AU - Janine Zwicklhuber
AU - Sarah Hochmann
AU - André Görgens
AU - Samir El Andaloussi
AU - Katharina Schallmoser
AU - Dirk Strunk
PY - 2026
DA - 2026/10/01
JO - Journal of extracellular vesicles
DO - 10.1002/jev2.70382
UR - https://europepmc.org/article/PMC/PMC13653646
AB - Extracellular vesicles (EVs) mediate cell‐to‐cell communication in development, health and disease. Heparin is a common component in human induced pluripotent stem cell (hiPSC) media but its impact on hiPSC‐EVs beyond stabilizing growth factors is unknown. Published evidence indicates heparin dose‐dependent EV uptake inhibition in heterotypic target cells. We asked if heparin affects hiPSC‐EV yield, storage, phenotype, or function. We used large‐scale hiPSC‐EV propagation to obtain pro‐angiogenic hiPSC‐EVs in presence or absence of escalating heparin doses and determined EV quantity, identity and functionality. Heparin delayed hiPSC colony‐confluence without significantly affecting hiPSC viability, pluripotency markers and proliferation. Significantly elevated tetraspanin+/flotillin+ hiPSC‐EV number (mean 367±31 EVs/cell/24 h at 200 IU heparin/mL) enabled efficient purification of > 1011/mL functional EVs at superior particle/protein ratio > 1010/mg. Heparin dose‐dependently inhibited EV uptake in hiPSC and endothelial progenitors, comparable to 5 IU/mL flavobacterium heparinase, and increased EV recovery after storage in NaCl but not in cell‐conditioned media. EVs obtained from hiPSC at 1% O2 with 200 IU/mL heparin maintained superior angiogenesis similarly to control hiPSC‐EVs obtained without heparin. We conclude that heparin inhibits hiPSC‐EV reuptake and stabilizes NaCl‐cryopreserved EVs thus boosting EV recovery while maintaining pro‐angiogenic function. Heparin presence and dose should therefore be documented particularly in PSC media.
SN - 2001-3078
ER -