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Article

Enhanced Platelet-Rich Plasma (ePRP) Stimulates Wound Healing through Effects on Metabolic Reprogramming in Fibroblasts

1
ICare Stem Cell Research Center, Taipei 100, Taiwan
2
Department of Physical Medicine and Rehabilitation, Taichung Veterans General Hospital, Taichung 40705, Taiwan
3
Department of Radiation Oncology, Taipei Medical University Hospital, Taipei 110301, Taiwan
4
Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan
5
Taipei Cancer Center, Taipei Medical University, Taipei 110301, Taiwan
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Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan
7
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan
8
International Master/Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan
*
Author to whom correspondence should be addressed.
Academic Editor: Cheorl-Ho Kim
Int. J. Mol. Sci. 2021, 22(23), 12623; https://doi.org/10.3390/ijms222312623
Received: 31 October 2021 / Revised: 15 November 2021 / Accepted: 16 November 2021 / Published: 23 November 2021
(This article belongs to the Special Issue Molecular Research of Glycolysis)
As a source of growth factors for expediting wound healing and tissue regeneration, plasma-rich plasma (PRP) has been extensively applied in diverse fields including orthopaedics, ophthalmology, oral and maxillofacial surgery, dentistry, and gynaecology. However, the function of PRP in metabolic regulations remains enigmatic. A standardized method was devised herein to enrich growth factors and to lyophilize it as enhanced PRP (ePRP) powder, which could become ubiquitously available without mechanical centrifugation in clinical practice. To identify metabolic reprogramming in human dermal fibroblasts under ePRP treatment, putative metabolic targets were identified by transcriptome profiling and validated for their metabolic effects and mechanism. ePRP does not only promote wound healing but re-aligns energy metabolism by shifting to glycolysis through stimulation of glycolytic enzyme activity in fibroblasts. On the contrary, oxygen consumption rates and several mitochondrial respiration activities were attenuated in ePRP-treated fibroblasts. Furthermore, ePRP treatment drives the mitochondrial resetting by hindering the mitochondrial biogenesis-related genes and results in a dampened mitochondrial mass. Antioxidant production was further increased by ePRP treatment to prevent reactive oxygen species formation. Besides, ePRP also halts the senescence progression of fibroblasts by activating SIRT1 expression. Importantly, the glycolytic inhibitor 2-DG can completely reverse the ePRP-enhanced wound healing capacity, whereas the mitochondrial inhibitor oligomycin cannot. This is the first study to utilize PRP for comprehensively investigating its effects on the metabolic reprogramming of fibroblasts. These findings indicate that PRP’s primary metabolic regulation is to promote metabolic reprogramming toward glycolytic energy metabolism in fibroblasts, preserving redox equilibrium and allowing anabolic pathways necessary for the healing and anti-ageing process. View Full-Text
Keywords: platelet-rich plasma; regenerative medicine; ageing; metabolic reprogramming; glycolysis platelet-rich plasma; regenerative medicine; ageing; metabolic reprogramming; glycolysis
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MDPI and ACS Style

Weng, H.-P.; Cheng, Y.-Y.; Lee, H.-L.; Hsu, T.-Y.; Chang, Y.-T.; Shen, Y.-A. Enhanced Platelet-Rich Plasma (ePRP) Stimulates Wound Healing through Effects on Metabolic Reprogramming in Fibroblasts. Int. J. Mol. Sci. 2021, 22, 12623. https://doi.org/10.3390/ijms222312623

AMA Style

Weng H-P, Cheng Y-Y, Lee H-L, Hsu T-Y, Chang Y-T, Shen Y-A. Enhanced Platelet-Rich Plasma (ePRP) Stimulates Wound Healing through Effects on Metabolic Reprogramming in Fibroblasts. International Journal of Molecular Sciences. 2021; 22(23):12623. https://doi.org/10.3390/ijms222312623

Chicago/Turabian Style

Weng, Hsin-Pei, Yuan-Yang Cheng, Hsin-Lun Lee, Tai-Yi Hsu, Yu-Tang Chang, and Yao-An Shen. 2021. "Enhanced Platelet-Rich Plasma (ePRP) Stimulates Wound Healing through Effects on Metabolic Reprogramming in Fibroblasts" International Journal of Molecular Sciences 22, no. 23: 12623. https://doi.org/10.3390/ijms222312623

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