Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 23, Pages -Publisher
MDPI
DOI: 10.3390/ijms232315408
Keywords
umbilical cord; mesenchymal stem cells; corneal endothelial cells; rabbit model of corneal endothelial dysfunction
Funding
- Korea Medical Device Development Fund - Korean government (Ministry of Science and ICT)
- Korea Medical Device Development Fund - Korean government (Ministry of Trade, Industry and Energy)
- Korea Medical Device Development Fund - Korean government (Ministry of Health Welfare)
- Korea Medical Device Development Fund - Korean government ( Ministry of Food and Drug Safety)
- Ministry of Science and ICT [1711138290, RS-2020-KD000148]
- Ministry of Health and Welfare (Republic of Korea)
- National Research Foundation of Korea [21C0723L1-12]
- Asan Institute for Life Sciences, Seoul, Republic of Korea [NRF-2022R1F1A1073895]
- [2022IP0066]
- [2021IP0061-2]
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This study demonstrated the differentiation of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) into corneal endothelial cells (CECs). The efficacy of MSC-induced CEC injection was investigated in a rabbit model of corneal endothelial dysfunction (CED). The results showed that MSC-induced CEC injection improved corneal opacity and neovascularization in the rabbit model.
Because of the limited differentiation capacity of human corneal endothelial cells (CECs), stem cells have emerged as a potential remedy for corneal endothelial dysfunction (CED). This study aimed to demonstrate the differentiation of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) into CECs and to investigate the efficacy of MSC-induced CEC injection into the anterior chamber in a rabbit model of CED. Human UC-MSCs were differentiated into CECs using medium containing glycogen synthase kinase 3 beta inhibitor and two types of Rho-associated protein kinase inhibitors. In the MSC-induced CECs, CEC-specific proteins were identified through immunohistochemistry and changes in CEC-specific gene expressions over time were confirmed through quantitative RT-PCR. When MSC-induced CECs were injected into a rabbit model of CED, corneal opacity and neovascularization were improved compared with the non-transplanted control or MSC injection group. We also confirmed that MSC-induced CECs were well engrafted as evidenced by human mitochondrial DNA in the central cornea of an animal model. Therefore, we demonstrated the differentiation of UC-MSCs into CECs in vitro and demonstrated the clinical efficacy of MSC-induced CEC injection, providing in vivo evidence that MSC-induced CECs have potential as a treatment option for CED.
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