Early Intervention in Ischemic Tissue with Oxygen Nanocarriers Enables Successful Implementation of Restorative Cell Therapies.

Autor: Diaz-Starokozheva L; Department of Biomedical Engineering, The Ohio State University, Columbus, OH USA.; Department of Surgery, The Ohio State University, Columbus, OH USA., Das D; Department of Biomedical Engineering, The Ohio State University, Columbus, OH USA., Gu X; William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH USA., Moore JT; Department of Biomedical Engineering, The Ohio State University, Columbus, OH USA., Lemmerman LR; Department of Biomedical Engineering, The Ohio State University, Columbus, OH USA., Valerio I; Plastic and Reconstructive Surgery, Massachusetts General Hospital, Boston, MA USA., Powell HM; Department of Biomedical Engineering, The Ohio State University, Columbus, OH USA.; Department of Materials Science and Engineering, The Ohio State University, Columbus, OH USA.; Research Department, Shriners Hospitals for Children, Cincinnati, OH USA., Higuita-Castro N; Department of Biomedical Engineering, The Ohio State University, Columbus, OH USA., Go MR; Department of Surgery, The Ohio State University, Columbus, OH USA., Palmer AF; William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH USA., Gallego-Perez D; Department of Biomedical Engineering, The Ohio State University, Columbus, OH USA.; Department of Surgery, The Ohio State University, Columbus, OH USA.
Jazyk: angličtina
Zdroj: Cellular and molecular bioengineering [Cell Mol Bioeng] 2020 May 29; Vol. 13 (5), pp. 435-446. Date of Electronic Publication: 2020 May 29 (Print Publication: 2020).
DOI: 10.1007/s12195-020-00621-4
Abstrakt: Background: Tissue ischemia contributes to necrosis and infection. While angiogenic cell therapies have emerged as a promising strategy against ischemia, current approaches to cell therapies face multiple hurdles. Recent advances in nuclear reprogramming could potentially overcome some of these limitations. However, under severely ischemic conditions necrosis could outpace reprogramming-based repair. As such, adjunctive measures are required to maintain a minimum level of tissue viability/activity for optimal response to restorative interventions.
Methods: Here we explored the combined use of polymerized hemoglobin (PolyHb)-based oxygen nanocarriers with Tissue Nano-Transfection (TNT)-driven restoration to develop tissue preservation/repair strategies that could potentially be used as a first line of care. Random-pattern cutaneous flaps were created in a mouse model of ischemic injury. PolyHbs with high and low oxygen affinity were synthesized and injected into the tissue flap at various timepoints of ischemic injury. The degree of tissue preservation was evaluated in terms of perfusion, oxygenation, and resulting necrosis. TNT was then used to deploy reprogramming-based vasculogenic cell therapies to the flaps via nanochannels. Reprogramming/repair outcomes were evaluated in terms of vascularity and necrosis.
Results: Flaps treated with PolyHbs exhibited a gradual decrease in necrosis as a function of time-to-intervention, with low oxygen affinity PolyHb showing the best outcomes. TNT-based intervention of the flap in combination with PolyHb successfully curtailed advanced necrosis compared to flaps treated with only PolyHb or TNT alone.
Conclusions: These results indicate that PolyHb and TNT technologies could potentially be synergistically deployed and used as early intervention measures to combat severe tissue ischemia.
(© Biomedical Engineering Society 2020.)
Databáze: MEDLINE
Externí odkaz: