# Bioinspired artificial nanovesicles engineered from 3D spheroid-cultured UC-MSCs enhance angiogenic activity in vitro: functional proof-of-concept for ischemic applications

**Authors:** Prakash Gangadaran, Ramya Lakshmi Rajendran, Ji Min Oh, Jaeyoung Son, Chae Moon Hong, Byeong-Cheol Ahn

PMC · DOI: 10.3389/fcell.2026.1695559 · Frontiers in Cell and Developmental Biology · 2026-02-06

## TL;DR

Artificial nanovesicles from 3D cultured stem cells boost blood vessel growth in lab tests, showing promise for treating poor blood flow.

## Contribution

3D-cultured UC-MSC-derived aNVs show enhanced angiogenic activity compared to 2D-derived aNVs.

## Key findings

- aNVS3D showed higher IL-6 and SDF-1α expression than aNVs2D.
- aNVS3D enhanced endothelial cell proliferation, migration, and tube formation more effectively.
- aNVS3D are potent inducers of angiogenesis for potential cell-free ischemia treatment.

## Abstract

Artificial nanovesicles (aNVs) derived from cells may mimic naturally secreted extracellular vesicles (EVs) and are becoming popular in biomedical research. We isolated aNVs from two-dimensional (2D)- and three-dimensional (3D)-cultured umbilical cord-derived mesenchymal stem cells (UC-MSCs) (aNVs2D and aNVs3D, respectively) and characterized them using Western blotting and electron microscopy. The aNVs3D showed higher expression of IL-6 and SDF-1α than aNVs2D. In vitro treatment with aNVs2D and aNVs3D resulted in their internalization into endothelial cells and the subsequent alteration of endothelial cell proliferation, migration, and tube formation. Both aNVs were positive for EVs and cell markers and were round in shape. Furthermore, aNVs3D treatment enhanced endothelial cell proliferation, migration, and tube formation more effectively than aNVs2D treatment. Our study demonstrates that aNVs3D are potent inducers of angiogenesis, indicating their potential in cell-free ischemia treatment.

Scientific diagram showing the process of creating artificial nanovesicles (aNVs) from two-dimensional and three-dimensional umbilical cord mesenchymal stem cells (UC-MSCs), extrusion steps, and their effects on endothelial cell proliferation, migration, and tube formation, with specific mention of increased IL-6 and SDF-1α for aNVs3D.

## Linked entities

- **Proteins:** IL6 (interleukin 6), cxcl12a (chemokine (C-X-C motif) ligand 12a (stromal cell-derived factor 1))

## Full-text entities

- **Genes:** FLOT1 (flotillin 1) [NCBI Gene 10211], CANX (calnexin) [NCBI Gene 821] {aka CNX, IP90, P90}, CD63 (CD63 molecule) [NCBI Gene 967] {aka AD1, HOP-26, ME491, MLA1, OMA81H, Pltgp40}, CXCL12 (C-X-C motif chemokine ligand 12) [NCBI Gene 6387] {aka IRH, PBSF, SCYB12, SDF1, TLSF, TPAR1}, PDCD6IP (programmed cell death 6 interacting protein) [NCBI Gene 10015] {aka AIP1, ALIX, DRIP4, HP95, MCPH29}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}
- **Diseases:** ischemia (MESH:D007511), Cancer (MESH:D009369), ischemic (MESH:D002545), CLI (MESH:D000089802), inflammation (MESH:D007249), necrosis (MESH:D009336), PAD (MESH:D058729), Ischemic diseases (MESH:D017202), vascular condition (MESH:D002561)
- **Chemicals:** Formvar (MESH:C013215), sodium dodecyl sulfate (MESH:D012967), CCK-8 (MESH:D012844), carbon (MESH:D002244), streptomycin (MESH:D013307), methanol (MESH:D000432), Iodixanol (MESH:C044834), PBS (MESH:D007854), glutaraldehyde (MESH:D005976), PVDF (MESH:C024865), DAPI (MESH:C007293), CO2 (MESH:D002245), lipid (MESH:D008055), paraformaldehyde (MESH:C003043), uranyl acetate (MESH:C005460), DMEM (-), crystal violet (MESH:D005840), penicillin (MESH:D010406)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** UC-MSCs2D — Homo sapiens (Human), Somatic stem cell (CVCL_3228), UC- — Homo sapiens (Human), Bladder carcinoma, Cancer cell line (CVCL_1783), SVEC4-10EHR1 — Mus musculus (Mouse), Transformed cell line (CVCL_4395)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12920476/full.md

## References

45 references — full list in the complete paper: https://tomesphere.com/paper/PMC12920476/full.md

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Source: https://tomesphere.com/paper/PMC12920476