Coculture of endothelial progenitor cells and mesenchymal stem cells enhanced their proliferation and angiogenesis through PDGF and Notch signaling
Open accessAbstract
The beneficial effects of combined use of mesenchymal stem cells (MSC s) and endothelial progenitor cells (EPC s) on tissue repair and regeneration after injury have been demonstrated, but the underlying mechanism remains incompletely understood. This study aimed to investigate the effects of direct contact coculture of human bone marrow‐derived EPCs (hEPCs)/human bone marrow‐derived MSCs (hMSC s) on their proliferation and angiogenic capacities and the underlying mechanism. hEPC s and hMSC s were cocultured in a 2D mixed monolayer or a 3D transwell membrane cell‐to‐cell coculture system. Cell proliferation was determined by Cell Counting Kit‐8. Angiogenic capacity was evaluated by in vitro angiogenesis assay. Platelet‐derived growth factor‐BB (PDGF‐BB), PDGF receptor neutralizing antibody (AB‐PDGFR), and DAPT (a γ‐secretase inhibitor) were used to investigate PDGF and Notch signaling. Cell proliferation was significantly enhanced by hEPC s/hMSC s 3D‐coculture and PDGF‐BB treatment, but inhibited by AB‐PDGFR. Expression of cyclin D1, PDGFR, Notch1, and Hes1 was markedly enhanced by PDGF‐BB but inhibited by DAPT. In vitro angiogenesis assay showed that hEPC s/hMSC s coculture and PDGF‐BB significantly enhanced angiogenic capacity, whereas AB‐PDGFR significantly reduced the angiogenic capacity. PDGF‐BB increased the expression of kinase insert domain receptor (KDR, an endothelial marker) and activated Notch1 signaling in cocultured cells, while DAPT attenuated the promoting effect of PDGF‐BB on KDR expression of hEPC s/hMSC s coculture. hEPC s/hMSC s coculture enhanced their proliferation and angiogenic capacities. PDGF and Notch signaling pathways participated in the promoting effects of hEPC s/hMSC s coculture, and there was crosstalk between these two signaling pathways. Our findings should aid understanding of the mechanism of beneficial effects of hEPC s/hMSC s coculture.
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The increased cartilage and mesenchymal lineage formation in SKOs receiving ECFCs may be attributed to secretion of growth factors such as platelet-derived growth factor and transforming growth factor-β by ECFCs, which promote mesenchymal lineage differentiation.
“that may be attributed to the secretion of growth factors such as platelet‐derived growth factor and transforming growth factor‐β by ECFCs, that promote mesenchymal lineage differentiation.[ 69 , 70 , 71 ]”
From Coordinated Development of Immune Cell Populations in Vascularized Skin Organoids from Human Induced Pluripotent Stem Cells (2025) · cites this paper as [70]
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- Authors
- Liang, T., Zhu, L., Gao, W., Gong, M., Ren, J., Yao, H., Wang, K., & Shi, D.
- Affiliations
- Third Affiliated Hospital of Sun Yat-sen University (CN)
- Prince Philip Dental Hospital (CN)
- Southern Medical University Shenzhen Hospital (CN)
- Corresponding author
- Shi, Dehai
- Venue
- FEBS Open Bio
- Publisher
- Wiley
- Published
- 2017-10-16
- Volume
- 7
- Issue
- 11
- Pages
- 1722-1736
- ISSN
- 2211-5463 (ISSN-L)
- PMC
- PMC5666384
- OpenAlex
- W2754079000
- Cited by
- 83
- References
- 40
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 7 · 2023: 6 · 2022: 18 · 2021: 20 · 2020: 11 · 2019: 10 · 2018: 3
- FWCI
- 3.77
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- FEBS Open Bio (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Natural Science Foundation of Guangdong Province (2014A030310046)
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- endothelial progenitor cells, mesenchymal stem cells, co-culture, angiogenesis, cell proliferation, PDGF-BB, PDGF receptor, Notch signaling, Notch1, Hes1, KDR, signaling crosstalk, bone marrow-derived cells, tissue regeneration
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