Advances in musculoskeletal tissue engineering: moving towards therapy

Abstract

Skeletal muscle can self-repair, but is unable to restore significant tissue loss, as consequence of trauma, congenital defects, tumor ablation or denervation. Intramuscular injection of autologous or allogenic derived myogenic cells (namely satellite cells and myoblasts) did not lead to efficient regeneration because of poor cell retention and survival, as well as immunorejection. In the last decade, tissue engineering looked at overcoming these problems by investigating alternative treatment options, i.e., the suspension of myogenic precursors in temporary matrix, formed by biodegradable and biocompatible materials. This approach allows to engineer custom architectured preconditioned implants, and locally deliver paracrine factors.This article reviews current and potential strategies for the repair of damaged muscle and suggests some innovative approaches for the translation to the clinical setting.

Keywords: biomaterial; muscle; niche; reconstruction; satellite cell; stem cell; tissue engineering.

Figure 1

The scheme shows the stem cell types, derived from muscle and non-muscle compartments, able to contribute to muscle regeneration (in the center, represented as green fluorescent protein-positive fibers, counterstained with laminin, the contribution of GFP + SCs when injected after injury, unpublished data). From the muscle compartment (left): satellite cells (SCs); mesoangioblasts, overexpressing β4-integrin and after administration of SDF-1 and TNFα; pericytes; skeletal muscle precursors (SMPs), selected for α1-integrin and CXCR4; muscle stem cells (MuSCs), selected for α7-integrin and CD34; side-population (SP) cells, selected for the ABCG2 transporter; PW1-cells, selected for PW1. From the non-muscle compartment (right): embryonic stem (ES) cells, positively selected for PDGFRα and negatively for Flk-1; amniotic fluid stem (AFS) cells, treated with 5-aza-2′-deoxycytidine; mesenchymal stem cells (MSCs); CD133(+) BM, mesenchymal cells from bone marrow selected for CD133.

Figure 2

The schemes explain the differences between the approaches of in vitro and in vivo tissue engineering. In vitro tissue engineering (left). A muscle biopsy is collected from an individual, stem cells are isolated and then expanded through cell culture techniques; they are then seeded on a 3D scaffold and a graft is generated and then transplanted. In vivo tissue engineering (right): a muscle biopsy is collected from an individual, then stem cells are isolated and immediately delivered on a 3D scaffold, that is promptly transplanted.