Author + information
- Received March 17, 2017
- Revision received August 16, 2017
- Accepted August 16, 2017
- Published online December 25, 2017.
- Fiona C. Lewis, BSc, PhDa,
- Beverley J. Cottle, BSc, PhDa,
- Victoria Shone, BSc, MSc, PhDa,
- Giovanna Marazzi, MDb,
- David Sassoon, PhDb,
- Cheyenne C.S. Tseng, MDc,
- Patricia Y.W. Dankers, PhDd,
- Steven A.J. Chamuleau, MD, PhDc,
- Bernardo Nadal-Ginard, MD, PhDa and
- Georgina M. Ellison-Hughes, BSc, PhDa,∗ ()
- aSchool of Basic & Medical Biosciences, Centre of Human & Aerospace Physiological Sciences & Centre for Stem Cells and Regenerative Medicine, Faculty of Life Sciences & Medicine, King’s College London, Guy’s Campus, London, United Kingdom
- bStem Cells and Regenerative Medicine UMRS 1166, Institute of Cardiometabolism and Nutrition, Université de Pierre et Marie Curie, Sorbonne Universités, Paris, France
- cDepartment of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, the Netherlands
- dSupramolecular Biomaterials for Translational Biomedical Science, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands
- ↵∗Address for correspondence:
Dr. Georgina M. Ellison-Hughes, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King’s College London, Shepherd’s House, Room 4.16, Guy’s Campus, London SE1 1UL, United Kingdom.
• Allogeneic PICs express and secrete an array of pro-regenerative paracrine factors that stimulate a regenerative response in a preclinical muscle injury model applicable to humans.
• Paracrine factors secreted by allogeneic PICs stimulate endogenous progenitor cell activation and differentiation, leading to accelerated and improved myofiber regeneration and microvessel formation.
• Allogeneic PICs survive long enough to exert their action before being cleared by the host immune system. Therefore, the cells transplanted are allogeneic but the regeneration is completely autologous.
• Administration of HGF and IGF-1 improves skeletal muscle regeneration, but not to the same extent as PIC transplantation.
Skeletal muscle-derived PW1pos/Pax7neg interstitial cells (PICs) express and secrete a multitude of proregenerative growth factors and cytokines. Utilizing a porcine preclinical skeletal muscle injury model, delivery of allogeneic porcine PICs (pPICs) significantly improved and accelerated myofiber regeneration and neocapillarization, compared with saline vehicle control-treated muscles. Allogeneic pPICs did not contribute to new myofibers or capillaries and were eliminated by the host immune system. In conclusion, allogeneic pPIC transplantation stimulated the endogenous stem cell pool to bring about enhanced autologous skeletal muscle repair and regeneration. This allogeneic cell approach is considered a cost-effective, easy to apply, and readily available regenerative therapeutic strategy.
This work was supported by the European Research Council, European Community 7th Framework project ENDOSTEM (contract number FP7-Health-2009-ENDOSTEM 241440 Activation of vasculature-associated stem cells and muscle stem cells for the repair and maintenance of muscle tissue). The authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Nadal-Ginard and Ellison-Hughes contributed equally to this work.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received March 17, 2017.
- Revision received August 16, 2017.
- Accepted August 16, 2017.
- 2017 The Authors