Human Laminin-111-Derived AG73 Increases Proliferation, Migration, and Differentiation of Human Myoblasts - A Promising Candidate in Regenerative Medicine

Sep 29, 2026

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Laminin 111 (LM-111) is an extracellular matrix glycoprotein in basement membranes, proposed for therapy of muscle diseases. LM-111 treatment reduces muscle damage, restores strength, alleviates inflammation, and promotes regeneration in murine and canine dystrophic models. LM-111 also boosts myoblast transplantation by increasing proliferation, survival, dispersion, and differentiation, potentially through matrikines generated by partial proteolysis. This study evaluates HuAG73, a human LM-derived peptide, on human myoblasts in vitro and in vivo.

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Abstract

Introduction

This article is licensed under CC-BY 4.0 [http://pubs.acs.org/journal/acsodf](http://pubs.acs.org/journal/acsodf) Article 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, and Ingo Riederer * Cite This: ACS Omega 2025, 10, 58480−58489 Read Online | | | | | | | | --- | --- | --- | --- | --- | --- | | ACCESS | Metrics & More | | Article Recommendations | | *sı Supporting Information | ABSTRACT: Laminin 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. ■ INTRODUCTION Laminin (LM), a major component of the basement membranes, is a heterotrimeric glycoprotein present as several distinct isoforms.1 The LM isoform 111 (LM-111) includes α 1, β1, and γ1 chains and is widely expressed in embryonic tissues. During skeletal muscle development, both LM-111 and LM-511 (α5β1γ1) are present in the dermomyotome and myotome, being subsequently replaced upon muscle maturation by LM-211 (α2β1γ 1) and LM-221 (α2β2γ 1), the predominant isoforms present in the basement membrane of the adult skeletal muscle.2,3 LM-211 and LM-221, as other components of the extracellular matrix, transmit force and provide structural support to the cell membrane during muscle contractions by binding to the α7β1 integrin receptor and the dystroglycan complex. During muscle regeneration, LM-111 and LM-511 are re-expressed4,5 as well as other LM isoforms (and their corresponding receptors). In adult skeletal muscle, regeneration after trauma or disease is carried out by the muscle stem cells (satellite cell, SC). In homeostasis, these cells are maintained in a quiescent state in a niche located between the membrane of the fibers (sarcolemma) and the basal lamina, in which the presence of soluble factors and ECM components provide a microenvironment that favor stem cell maintenance.6 After muscle injury, the LM-111 isoform is transiently deposited within the SC niche, stimulating SC expansion and self-renewal.5 Both recombinant or purified LM-111 have been used as a protein-based therapeutic strategy, demonstrating an ability to increase muscle strength and decrease muscle inflammation and damage in animal models of Duchenne muscular dystrophy (DMD) and α7 integrin deficient mice.7−11 In addition, human myoblasts when mixed with LM-111 and injected into damaged murine muscles, showed enhanced survival, migration, and differentiation,4, 12 suggesting a potential benefit of using LM-111 as an adjuvant for cell therapy. LMs and other ECM components can be naturally cleaved by proteinases, such as metalloproteinases (MPPs), generating peptides that can

FAQs

What biological effects does LM-111 have on muscle regeneration and myoblast transplantation?

LM-111 reduces muscle damage, restores muscle strength, alleviates inflammation, and promotes regeneration. It also improves myoblast transplantation efficacy by increasing proliferation, survival, dispersion, and differentiation of transplanted myoblasts.

What is HuAG73, and how is it related to laminin?

HuAG73 is a peptide derived from human laminin. It is generated conceptually via proteolysis-based production of matrikines from laminin, and the study investigates its activity on human myoblasts.

How does HuAG73 compare to LM-111 for therapeutic potential?

HuAG73 offers a significant advantage over LM-111 due to its smaller size and simpler structure. It promotes adhesion, proliferation, migration, and fusion in human myoblast culture and mimics LM-111 in a myoblast transplantation assay.

Sep 29, 2026

Upload by Fahsai