# Embryonic lineage-specific iPSC-derived mesenchymal stem/stromal cells exhibit different morphologies and intrinsic functions

**Authors:** Linh Nguyen, Souta Motoike, Denise Zujur, Keiko Yoshizawa, Yasuhiro Takashima, Akiyoshi Uezumi, Kazuhiro Furuhashi, Shoichi Maruyama, Yonghui Jin, Junya Toguchida, Hidetoshi Sakurai, Makoto Ikeya

PMC · DOI: 10.1016/j.isci.2025.114482 · 2025-12-18

## TL;DR

Researchers found that mesenchymal stem cells derived from induced pluripotent stem cells differ in their abilities based on their embryonic origin, which could improve regenerative medicine.

## Contribution

This study shows that lineage-specific iPSC-derived MSCs have distinct functional and morphological traits, offering a new approach for generating consistent MSCs.

## Key findings

- MSCs derived from different embryonic lineages showed varied osteogenic, chondrogenic, and adipogenic potentials.
- Transcriptomic analysis revealed distinct clusters among lineage-specific iMSCs.
- iMSCs showed a high correlation with tissue-derived MSCs despite their differences.

## Abstract

Mesenchymal stem/stromal cells (MSCs) have great potential in regenerative medicine owing to their multilineage differentiation capacity. However, tissue-derived MSCs (tMSCs) exhibit inconsistent characteristics. Although induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) are a potential solution, the effect of different embryonic lineages on their properties remains unknown. We generated MSCs from human iPSCs via five lineage-specific routes: cranial neural crest, trunk neural crest, paraxial mesoderm (somite), lateral plate mesoderm, and limb mesenchyme. All types met established MSC criteria yet differed in morphology, proliferation, and differentiation capacity. Somite-, cranial neural crest-, and limb mesenchyme-derived MSCs showed higher osteogenic potential, whereas somite-derived MSCs also showed high chondrogenic potential but were prone to hypertrophy. Limb mesenchyme-derived MSCs showed the highest adipogenic potential. Transcriptomic profiles indicated distinct clusters within iMSCs. Despite variances, a high correlation level existed between iMSCs and tMSCs. Therefore, iMSCs are potential alternatives to tMSCs in regenerative medicine.

•iMSCs were differentiated from the same iPSC line via 5 different embryonic origins•Different iMSC types displayed different intrinsic characteristics•Somite-derived iMSCs (SM-iMSCs) showed higher osteogenic differentiation potential•Cranial neural crest-derived iMSCs (cNCC-iMSCs) have more chondrogenic potential

iMSCs were differentiated from the same iPSC line via 5 different embryonic origins

Different iMSC types displayed different intrinsic characteristics

Somite-derived iMSCs (SM-iMSCs) showed higher osteogenic differentiation potential

Cranial neural crest-derived iMSCs (cNCC-iMSCs) have more chondrogenic potential

Cell biology; Developmental biology

## Linked entities

- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Diseases:** hypertrophy (MESH:D006984)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12803943/full.md

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Source: https://tomesphere.com/paper/PMC12803943