Abstract

BackgroundCell-transplantation therapies have attracted attention as treatments for skeletal-muscle disorders; however, such research has been severely limited by poor cell survival. Tissue engineering offers a potential solution to this problem by providing biomaterial adjuvants that improve survival and engraftment of donor cells.MethodsIn this study, we investigated the use of intra-muscular transplantation of mesoangioblasts (vessel-associated progenitor cells), delivered with an injectable hydrogel biomaterial directly into the tibialis anterior (TA) muscle of acutely injured or dystrophic mice. The hydrogel cell carrier, made from a polyethylene glycol-fibrinogen (PF) matrix, is polymerized in situ together with mesoangioblasts to form a resorbable cellularized implant.ResultsMice treated with PF and mesoangioblasts showed enhanced cell engraftment as a result of increased survival and differentiation compared with the same cell population injected in aqueous saline solution.ConclusionBoth PF and mesoangioblasts are currently undergoing separate clinical trials: their combined use may increase chances of efficacy for localized disorders of skeletal muscle.

Highlights

  • Cell-transplantation therapies have attracted attention as treatments for skeletal-muscle disorders; such research has been severely limited by poor cell survival

  • We evaluated an approach based upon local delivery of mesoangioblasts that was facilitated by a semi-synthetic hydrogel made from polyethylene glycol (PEG) and fibrinogen

  • We choose mesoangioblasts, as our myogenic stem/progenitor cell

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Summary

Introduction

Cell-transplantation therapies have attracted attention as treatments for skeletal-muscle disorders; such research has been severely limited by poor cell survival. Skeletal muscles are primarily responsible for controlling voluntary movement and posture They can self-repair in response to moderate injuries, but are not able to regenerate when significant loss of tissue occurs in extensive trauma or surgery. They cannot sustain repeated cycles of degeneration/regeneration, such as occurs in severe forms of muscular dystrophy [1], which are difficult diseases to treat. Such conditions affect the treating muscular dystrophies, stem-cell transplantation is becoming a promising clinical option [7]. A phase I/II clinical trial based on intra-arterial delivery of donor-derived mesoangioblasts is currently ongoing in children affected by Duchene Muscular Dystrophy at the San Raffaele Hospital in Milan (EudraCT no. 2011-000176-33)

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