Myogenic progenitor cell transplantation for muscle regeneration following hindlimb ischemia and reperfusion.

Animals Hindlimb Ischemia / therapy Mice Muscle Development Muscle, Skeletal Reperfusion Reperfusion Injury / therapy Stem Cell Transplantation
Ischemia-reperfusion injury Muscle regeneration Myogenic progenitor cells Satellite cells Stem cell Transplantation

Journal

Stem cell research & therapy
ISSN: 1757-6512
Titre abrégé: Stem Cell Res Ther
Pays: England
ID NLM: 101527581

Informations de publication

Date de publication:
24 02 2021
Historique:
received: 04 12 2020
accepted: 02 02 2021
entrez: 25 2 2021
pubmed: 26 2 2021
medline: 9 7 2021
Statut: epublish

Résumé

Muscle is severely affected by ischemia/reperfusion injury (IRI). Quiescent satellite cells differentiating into myogenic progenitor cells (MPC) possess a remarkable regenerative potential. We herein established a model of local application of MPC in murine hindlimb ischemia/reperfusion to study cell engraftment and differentiation required for muscle regeneration. A clamping model of murine (C57b/6 J) hindlimb ischemia was established to induce IRI in skeletal muscle. After 2 h (h) warm ischemic time (WIT) and reperfusion, reporter protein expressing MPC (TdTomato or Luci-GFP, 1 × 10 2h WIT induced severe IRI on muscle, and muscle fiber regeneration as per histopathology within 14 days after injury. Bioluminescence in vivo imaging demonstrated reporter protein signals of MPC in 2h WIT animals and controls over the study period (75 days). Bioluminescence signals were detected at the injection site and increased over time. TdTomato expressing MPC and myofibers were visible in host tissue on postoperative days 2 and 14, respectively, suggesting that injected MPC differentiated into muscle fibers. Higher reporter protein signals were found after 2h WIT compared to controls without ischemia, indicative for enhanced growth and/or engraftment of MPC injected into IRI-affected muscle antagonizing muscle damage caused by IRI. WIT-induced IRI in muscle requests increased numbers of injected MPC to engraft and persist, suggesting a possible rational for cell therapy to antagonize IRI. Further investigations are needed to evaluate the regenerative capacity and therapeutic advantage of MPC in the setting of ischemic limb injury.

Sections du résumé

BACKGROUND
Muscle is severely affected by ischemia/reperfusion injury (IRI). Quiescent satellite cells differentiating into myogenic progenitor cells (MPC) possess a remarkable regenerative potential. We herein established a model of local application of MPC in murine hindlimb ischemia/reperfusion to study cell engraftment and differentiation required for muscle regeneration.
METHODS
A clamping model of murine (C57b/6 J) hindlimb ischemia was established to induce IRI in skeletal muscle. After 2 h (h) warm ischemic time (WIT) and reperfusion, reporter protein expressing MPC (TdTomato or Luci-GFP, 1 × 10
RESULTS
2h WIT induced severe IRI on muscle, and muscle fiber regeneration as per histopathology within 14 days after injury. Bioluminescence in vivo imaging demonstrated reporter protein signals of MPC in 2h WIT animals and controls over the study period (75 days). Bioluminescence signals were detected at the injection site and increased over time. TdTomato expressing MPC and myofibers were visible in host tissue on postoperative days 2 and 14, respectively, suggesting that injected MPC differentiated into muscle fibers. Higher reporter protein signals were found after 2h WIT compared to controls without ischemia, indicative for enhanced growth and/or engraftment of MPC injected into IRI-affected muscle antagonizing muscle damage caused by IRI.
CONCLUSION
WIT-induced IRI in muscle requests increased numbers of injected MPC to engraft and persist, suggesting a possible rational for cell therapy to antagonize IRI. Further investigations are needed to evaluate the regenerative capacity and therapeutic advantage of MPC in the setting of ischemic limb injury.

Identifiants

DOI: 10.1186/s13287-021-02208-w PMID: 33627196 PMC: PMC7905585
pubmed: 33627196
doi: 10.1186/s13287-021-02208-w
pii: 10.1186/s13287-021-02208-w
pmc: PMC7905585
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

146

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Auteurs

Franka Messner (F)

Daniel Swarovski Research Laboratory (DSL), Department of Visceral, Transplant and Thoracic Surgery (VTT), Center of Operative Medicine, Medical University of Innsbruck (MUI), Innrain 66, 6020, Innsbruck, Austria.

Marco Thurner (M)

Daniel Swarovski Research Laboratory (DSL), Department of Visceral, Transplant and Thoracic Surgery (VTT), Center of Operative Medicine, Medical University of Innsbruck (MUI), Innrain 66, 6020, Innsbruck, Austria.
Innovacell Biotechnologie AG, Innsbruck, Austria.

Jule Müller (J)

Daniel Swarovski Research Laboratory (DSL), Department of Visceral, Transplant and Thoracic Surgery (VTT), Center of Operative Medicine, Medical University of Innsbruck (MUI), Innrain 66, 6020, Innsbruck, Austria.

Michael Blumer (M)

Department of Anatomy, Histology and Embryology, Division of Clinical and Functional Anatomy, Medical University of Innsbruck, Innsbruck, Austria.

Julia Hofmann (J)

Daniel Swarovski Research Laboratory (DSL), Department of Visceral, Transplant and Thoracic Surgery (VTT), Center of Operative Medicine, Medical University of Innsbruck (MUI), Innrain 66, 6020, Innsbruck, Austria.

Rainer Marksteiner (R)

Innovacell Biotechnologie AG, Innsbruck, Austria.

Sebastien Couillard-Despres (S)

Institute of Experimental Neuroregeneration, Spinal Cord Injury and Tissue Regeneration, Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria.
Austrian Cluster for Tissue Regeneration, Vienna, Austria.

Jakob Troppmair (J)

Daniel Swarovski Research Laboratory (DSL), Department of Visceral, Transplant and Thoracic Surgery (VTT), Center of Operative Medicine, Medical University of Innsbruck (MUI), Innrain 66, 6020, Innsbruck, Austria.

Dietmar Öfner (D)

Daniel Swarovski Research Laboratory (DSL), Department of Visceral, Transplant and Thoracic Surgery (VTT), Center of Operative Medicine, Medical University of Innsbruck (MUI), Innrain 66, 6020, Innsbruck, Austria.

Stefan Schneeberger (S)

Daniel Swarovski Research Laboratory (DSL), Department of Visceral, Transplant and Thoracic Surgery (VTT), Center of Operative Medicine, Medical University of Innsbruck (MUI), Innrain 66, 6020, Innsbruck, Austria. Stefan.Schneeberger@i-med.ac.at.
Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria. Stefan.Schneeberger@i-med.ac.at.

Theresa Hautz (T)

Daniel Swarovski Research Laboratory (DSL), Department of Visceral, Transplant and Thoracic Surgery (VTT), Center of Operative Medicine, Medical University of Innsbruck (MUI), Innrain 66, 6020, Innsbruck, Austria. Theresa.Hautz@i-med.ac.at.

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Classifications MeSH

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