Human Laminin-111-Derived AG73 Increases Proliferation, Migration, and Differentiation of Human Myoblasts: A Promising Candidate in Regenerative Medicine.
Samuel Iwao Maia Horita, Mona Bensalah, Anne Bigot, Kamel Mamchaoui, Gillian S Butler Browne, Daniela Gois Beghini, Wilson Savino, Capucine Trollet, Vincent Mouly, Elisa Negroni, Andrea Henriques Pons, Ingo Riederer
Abstract
Open AccessLaminin 111 (LM-111) is an extracellular matrix (ECM) glycoprotein found in basement membranes and proposed for muscle disease therapy. LM-111 treatment reduces muscle damage, restores muscle strength, alleviates inflammation, and promotes regeneration in murine and canine dystrophic models. LM-111 also improves myoblast transplantation (MT) efficacy by inducing higher proliferation, survival, dispersion, and differentiation of transplanted myoblasts. LM can undergo partial proteolysis and produce peptides called matrikines that modulate cell activity and trigger distinct biological responses from the full-length glycoproteins. In this study, we investigated the biological activity of the HuAG73 peptide, derived from the human LM, on human myoblasts, both in vitro and in vivo, using immunodeficient mice. The HuAG73 peptide offers a significant advantage over LM-111 due to its smaller size and simpler structure. HuAG73 promoted adhesion, proliferation, migration, and fusion of human myoblasts in culture. It also mimicked LM-111 in an MT assay. In conclusion, HuAG73 is a novel, relevant therapeutic candidate molecule for treating muscle diseases.