Trophic actions of bone marrow-derived mesenchymal stromal cells for muscle repair/regeneration

Abstract

Bone marrow-derived mesenchymal stromal cells (BM-MSCs) represent the leading candidate cell in tissue engineering and regenerative medicine. These cells can be easily isolated, expanded in vitro and are capable of providing significant functional benefits after implantation in the damaged muscle tissues. Despite their plasticity, the participation of BM-MSCs to new muscle fiber formation is controversial; in fact, emerging evidence indicates that their therapeutic effects occur without signs of long-term tissue engraftment and involve the paracrine secretion of cytokines and growth factors with multiple effects on the injured tissue, including modulation of inflammation and immune reaction, positive extracellular matrix (ECM) remodeling, angiogenesis and protection from apoptosis. Recently, a new role for BM-MSCs in the stimulation of muscle progenitor cells proliferation has been demonstrated, suggesting the potential ability of these cells to influence the fate of local stem cells and augment the endogenous mechanisms of repair/regeneration in the damaged tissues.

Figure 1

Bone marrow-derived mesenchymal stromal cells (BM-MSCs) stimulate proliferation of muscle progenitor cells. Representative superimposed differential interference contrast (DIC) and confocal fluorescence images showing the pyrimidine analogue EdU (5-ethynyl-2'-deoxyuridine) staining (green) in the nuclei of proliferating murine C2C12 skeletal myoblasts or murine neonatal cardiomyocytes in single and co-culture for 24 h with mouse Dil-labeled BM-MSCs (red). Note the higher number of proliferating cells in the co-culture systems.

Scheme 1

Therapeutic paracrine effects of bone marrow derived mesenchymal stromal cells (BM-MSCs) for skeletal and cardiac muscle repair/regeneration. Abbreviations: ECM: Extracellular matrix; FGF: Fibroblast growth factor; HGF: Hepatocyte growth factor; IL-1: Interleukin 1; IL 6: Interleukin-6; IL-10: Interleukin 10; MMPs: Matrix metalloproteinases; PDGF: Platelet derived growth factor; TGF-β: transforming growth factor-β; VEGF: Vascular endothelial growth factor; SDF-1: stromal derived factor-1; IL-1RA: interleukin 1 receptor antagonist; PGE2: prostaglandin E2; LIF: leukemia inhibitory factor; NO: Nitric oxide.