Inorganic polyphosphate in platelet rich plasma accelerates re-epithelialization in vitro and in vivo

Bonnie C Carney; Cynthia M Simbulan-Rosenthal; Anirudh Gaur; Benjamin J Browne; Manish Moghe; Elliott Crooke; Lauren T Moffatt; Jeffrey W Shupp; Dean S Rosenthal

doi:10.1016/j.reth.2020.07.004

Inorganic polyphosphate in platelet rich plasma accelerates re-epithelialization in vitro and in vivo

Regen Ther. 2020 Aug 6:15:138-148. doi: 10.1016/j.reth.2020.07.004. eCollection 2020 Dec.

Authors

Bonnie C Carney^{1

2}, Cynthia M Simbulan-Rosenthal¹, Anirudh Gaur¹, Benjamin J Browne², Manish Moghe¹, Elliott Crooke¹, Lauren T Moffatt^{1

2}, Jeffrey W Shupp^{1

2

3

4}, Dean S Rosenthal¹

Affiliations

¹ Department of Biochemistry and Molecular and Cellular Biology, Georgetown University School of Medicine, Washington, DC, USA.
² Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC, USA.
³ The Burn Center, Department of Surgery, MedStar Washington Hospital Center, Washington, DC, USA.
⁴ Department of Surgery, Georgetown University School of Medicine, Washington, DC, USA.

Abstract

Wound healing requires well-coordinated events including hemostasis, inflammation, proliferation, and remodeling. Delays in any of these stages leads to chronic wounds, infections, and hypertrophic scarring. Burn wounds are particularly problematic, and may require intervention to ensure timely progression to reduce morbidity and mortality. To accelerate burn wound healing, Platelet-Rich Plasma (PRP)¹ can be of value, since platelets release growth factor proteins and inorganic polyphosphates (polyP) that may be integral to wound healing. We used polyP-depleted keratinocyte (HaCaT) and fibroblast cell culture models to determine cell proliferation and scratch-wound repair to determine if polyP, platelet lysate, or combined treatment could accelerate wound healing. While polyP and PRP significantly reduced the open scratch-wound area in fibroblasts and keratinocytes, polyP had no effect on keratinocyte or fibroblast proliferation. PRP was also evaluated as a treatment in a murine model of full thickness wound healing in vivo, including a treatment in which PRP was supplemented with purified polyP. PRP induced significantly more rapid re-epithelialization by Day 3. Pure polyP enhanced the effects of PRP on epithelial tongues, which were significantly elongated in the PRP + high-dose polyP treatment groups compared to PRP alone. Thus, PRP and polyP may serve as an effective therapeutic combination for treating wounds.

Keywords: Inorganic polyphosphate; Keratinocytes; PPX1 exopolyphosphatase; Wound healing; endopolyphosphatase, PPN; epidermal growth factor, EGF; exopolyphosphatase, PPX; human foreskin fibroblasts, HFF; mammalian target of rapamycin, mTOR; platelet-derived growth factor, PDGF; platelet-poor plasma, PPP; platelet-rich plasma, PRP; polyP kinase, PPK; polyphosphates, polyP; reactive oxygen species, ROS; total body surface area, TBSA; transforming growth factor beta, TGFβ; vacuolar transporter chaperone 4, VTC4.