Therapeutic Applications of Mesenchymal Stem Cell Loaded with Gold Nanoparticles for Regenerative Medicine

Author:

Cheng Wen-Yu1234,Yang Meng-Yin14ORCID,Yeh Chun-An5,Yang Yi-Chin1ORCID,Chang Kai-Bo5,Chen Kai-Yuan1,Liu Szu-Yuan1,Tang Chien-Lun1,Shen Chiung-Chyi1,Hung Huey-Shan56ORCID

Affiliation:

1. Department of Minimally Invasive Skull Base Neurosurgery, Neurological Institute, Taichung Veterans General Hospital, Taichung 407204, Taiwan

2. Department of Physical Therapy, Hung Kuang University, Taichung 433304, Taiwan

3. Institute of Biomedical Sciences, National Chung Hsing University, Taichung 402202, Taiwan

4. Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 402202, Taiwan

5. Graduate Institute of Biomedical Science, China Medical University, Taichung 404333, Taiwan

6. Translational Medicine Research, China Medical University Hospital, Taichung 404327, Taiwan

Abstract

In the present study, the various concentrations of AuNP (1.25, 2.5, 5, 10 ppm) were prepared to investigate the biocompatibility, biological performances and cell uptake efficiency via Wharton’s jelly mesenchymal stem cells and rat model. The pure AuNP, AuNP combined with Col (AuNP-Col) and FITC conjugated AuNP-Col (AuNP-Col-FITC) were characterized by Ultraviolet–visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR) and Dynamic Light Scattering (DLS) assays. For in vitro examinations, we explored whether the Wharton’s jelly MSCs had better viability, higher CXCR4 expression, greater migration distance and lower apoptotic-related proteins expression with AuNP 1.25 and 2.5 ppm treatments. Furthermore, we considered whether the treatments of 1.25 and 2.5 ppm AuNP could induce the CXCR4 knocked down Wharton’s jelly MSCs to express CXCR4 and reduce the expression level of apoptotic proteins. We also treated the Wharton’s jelly MSCs with AuNP-Col to investigate the intracellular uptake mechanisms. The evidence demonstrated the cells uptake AuNP-Col through clathrin-mediated endocytosis and the vacuolar-type H+-ATPase pathway with good stability inside the cells to avoid lysosomal degradation as well as better uptake efficiency. Additionally, the results from in vivo examinations elucidated the 2.5 ppm of AuNP attenuated foreign body responses and had better retention efficacy with tissue integrity in animal model. In conclusion, the evidence demonstrates that AuNP shows promise as a biosafe nanodrug delivery system for development of regenerative medicine coupled with Wharton’s jelly MSCs.

Funder

National Science and Technology Council

Ministry of Science and Technology

Publisher

MDPI AG

Subject

Pharmaceutical Science

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