On July 14, 2026, the Institute of Medical Biotechnology welcomed Dr. Leonit Kiriaev, Senior Research Officer in the Muscle Research Group at the Murdoch Children’s Research Institute (MCRI) in Melbourne, Australia, as part of the ongoing DAAD-funded academic exchange between MBT and MCRI. His seminar, titled „Trained to repair: modelling a ‚healthy regenerative state‘ using mouse injury and human co-culture systems,“ offered a comprehensive view of his group’s work bridging rodent physiology and human tissue engineering.
Two Faces of Repeated Muscle Stress
Dr. Kiriaev opened by framing a central paradox in muscle biology: repeated mechanical stress can either strengthen muscle or destroy it, depending on context. In healthy muscle, the well-known „repeat bout effect“ means that after an initial bout of exercise-induced damage, the same stress becomes progressively less damaging and produces a stronger muscle. In Duchenne muscular dystrophy (DMD) — a disease affecting roughly 1 in 5,000 live male births and caused by loss of the structural protein dystrophin — the same repeated contractile stress instead drives chronic, failed cycles of degeneration and regeneration, ultimately causing progressive loss of ambulation and cardiac/respiratory function.
Modelling Repeated Injury in Healthy Muscle
To ask whether healthy muscle could be pushed past this protective adaptation into a harmful state, his team built a repeated-injury model in mice using notexin, a myotoxin derived from tiger snake venom, injected into the tibialis anterior at 7-day intervals across three rounds of injury and regeneration. Rather than deteriorating, muscle subjected to three rounds of notexin injury (3X) became dramatically more resistant to subsequent eccentric contraction damage: extensor digitorum longus (EDL) muscles from 3X-injured mice showed far less eccentric force loss during a standardized damage protocol (20% strain at 3-minute intervals) and a markedly stronger, near-complete recovery within 60 minutes — clearly outperforming both undamaged muscle and muscle injured only once.
A New Molecular Identity: „Healthy Regenerative Memory“
Digging into the mechanism, Dr. Kiriaev’s team found that repeatedly injured fibres became smaller, more uniform, and shifted their contractile identity from fast glycolytic (Type 2B) toward slower, more oxidative fibre types (2A/Type 1) — a shift confirmed at both the transcriptomic and proteomic level. Alongside this fibre-type shift, the extracellular matrix (ECM) underwent selective reorganization rather than fibrotic scarring, helping redistribute mechanical strain during subsequent eccentric contractions. Together, these coordinated changes define what his team terms a „healthy regenerative memory“ — a durable tissue state that encodes the history of prior injury and results in lasting protection against future mechanical damage.
Extending the Model to Human Tissue
Beyond the mouse work, Dr. Kiriaev presented his group’s progress engineering human 3D muscle organoids that incorporate induced macrophages (iMACs) alongside myogenic cells. Strikingly, iMAC co-culture with macrophage colony-stimulating factor (MCSF) significantly boosted tetanic force output over 21 days of tissue maturation, and macrophage-containing organoids recovered from induced injury faster and more completely than muscle tissue alone — recovering to baseline force within one day versus two days, with less initial force loss (13% vs. 24%). This human-relevant platform, developed using a custom localized injury device, positions MCRI to study repeated injury and regenerative recovery in a system directly relevant to neuromuscular disease patients.