Transplantation of Allogeneic PW1pos/Pax7neg Interstitial Cells Enhance Endogenous Repair of Injured Porcine Skeletal Muscle

Fiona C Lewis; Beverley J Cottle; Victoria Shone; Giovanna Marazzi; David Sassoon; Cheyenne C S Tseng; Patricia Y W Dankers; Steven A J Chamuleau; Bernardo Nadal-Ginard; Georgina M Ellison-Hughes

doi:10.1016/j.jacbts.2017.08.002

Transplantation of Allogeneic PW1^pos/Pax7^neg Interstitial Cells Enhance Endogenous Repair of Injured Porcine Skeletal Muscle

JACC Basic Transl Sci. 2017 Dec 13;2(6):717-736. doi: 10.1016/j.jacbts.2017.08.002. eCollection 2017 Dec.

Affiliations

¹ School 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.
² Stem Cells and Regenerative Medicine UMRS 1166, Institute of Cardiometabolism and Nutrition, Université de Pierre et Marie Curie, Sorbonne Universités, Paris, France.
³ Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, the Netherlands.
⁴ Supramolecular Biomaterials for Translational Biomedical Science, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.

Abstract

Skeletal muscle-derived PW1^pos/Pax7^neg 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.

Keywords: BrdU, 5-bromo-2′-deoxyuridine; CM, pPIC conditioned medium; CSA, cross sectional area; CSC, cardiac stem cell; CTRL, control; CTX, cardiotoxin; DAPI, 4′,6-diamidino-2-phenylindole; DMEM, Dulbecco’s Modified Eagle's medium; FBS, fetal bovine serum; GFPpPIC, GFP-positive porcine PW1pos/Pax7neg interstitial cell; GM, growth medium; HUVEC, human umbilical vein endothelial cell; HVG, hematoxylin and van Gieson; ICM, heat-inactivated conditioned medium; IV, intravenous; MHC, myosin heavy chain; MI, myocardial infarction; P, passage; PBMC, peripheral blood mononuclear cell; PBS, phosphate buffered saline; PIC, PW1pos/Pax7neg interstitial cell; PICs; TA, tibialis anterior; UM, unconditioned medium; allogeneic progenitor cells; growth factors; nMHC, neonatal myosin heavy chain; pPIC, porcine PW1pos/Pax7neg interstitial cell; porcine preclinical model; qRT-PCR, quantitative reverse transcription polymerase chain reaction; regeneration; skeletal muscle; vWF, Von Willebrand factor.