# NRP2+ human mesenchymal stem cells have stemness-associated properties

**Authors:** Kotaro Tanaka, Rintaro Yoshikawa, Satoru Miyagi, Takashi Suyama, Hiromi Miyauchi, Yuko Kato, Kenichi Miyamoto, Yumi Matsuzaki

PMC · DOI: 10.1186/s41232-025-00376-3 · Inflammation and Regeneration · 2025-04-28

## TL;DR

This study identifies NRP2 as a marker for high-quality mesenchymal stem cells with better growth and healing abilities.

## Contribution

The study introduces NRP2 as a novel cell surface marker for identifying superior mesenchymal stem cells.

## Key findings

- NRP2+ MSCs show enhanced proliferation, differentiation, and migration compared to NRP2− MSCs.
- Activation of VEGF-C/NRP2 signaling improves MSC proliferation and differentiation.
- NRP2 is proposed as a marker for high-quality MSCs in regenerative medicine.

## Abstract

The clinical application of mesenchymal stem cells (MSCs) has garnered attention due to their remarkable capacity to differentiate into adipocytes, chondrocytes, and osteoblasts. However, the quality of MSC culture varies from batch to batch, which poses challenges in ensuring consistent cellular quality across batches. Consequently, it becomes imperative to identify specific markers that can distinguish superior and slightly inferior MSCs.

Human bone marrow-derived MSC clones were isolated and subjected to flow cytometry analysis to assess the expression of NRP2, VEGFR, and plexinA1. The osteogenic and adipogenic differentiation potentials were evaluated using Alizarin Red S and Oil Red O staining, respectively. Furthermore, the migration capacity was assessed through the scratch healing assay.

Nine out of twenty MSC clones significantly expressed NRP2. NRP2-expressing MSC clones (NRP2+ MSCs) retained superior proliferation and differentiation capacities, along with increased migratory capacity compared to non-expressing MSC clones (NRP2− MSCs). In addition, the activation of VEGF-C/NRP2 signaling augmented the potential of MSCs in cell proliferation and differentiation.

In contrast to NRP2− MSCs, NRP2+ MSCs exhibited superior proliferation, differentiation abilities, and migration capacity. Moreover, the stimulation of VEGF-C/NRP2 signaling further enhanced the proliferation and differentiation rates, indicating a role of NRP2 in the maintenance of MSC stemness. Hence, NRP2 holds potential as a cell surface marker for identifying beneficial MSCs for regenerative medicine.

## Linked entities

- **Genes:** NRP2 (neuropilin 2) [NCBI Gene 8828], KDR (kinase insert domain receptor) [NCBI Gene 3791], PLXNA1 (plexin A1) [NCBI Gene 5361]
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** PLXNA1 (plexin A1) [NCBI Gene 5361] {aka DWOPNED, NOV, NOVP, PLEXIN-A1, PLXN1}, NRP2 (neuropilin 2) [NCBI Gene 8828] {aka NP2, NPN2, PRO2714, VEGF165R2}, VEGFC (vascular endothelial growth factor C) [NCBI Gene 7424] {aka Flt4-L, LMPH1D, LMPHM4, VRP}, KDR (kinase insert domain receptor) [NCBI Gene 3791] {aka CD309, FLK1, VEGFR, VEGFR2}
- **Chemicals:** Oil Red O (MESH:C011049), Alizarin Red S (MESH:C004468)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12036193/full.md

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Source: https://tomesphere.com/paper/PMC12036193