Skeletal Muscle Regeneration: A Case Study

ABSTRACT: Skeletal muscle is able to repair itself through regeneration.
However, an injured muscle often does not fully recover its strength because complete muscle regeneration is hindered by the development of fibrosis.
Biological approaches to improve muscle healing by enhancing muscle regeneration and reducing the formation of fibrosis are being investigated.
Previously, we have determined that insulin-like growth factor–1 (IGF-1) can improve muscle regeneration in injured muscle. We also have investigated the use of an antifibrotic agent, decorin, to reduce muscle fibrosis following injury. The aim of this study was to combine these two therapeutic methods in an attempt to develop a new biological approach to promote efficient
healing
Muscle Nerve 28: 365–372, 2003

IMPROVEMENT OF MUSCLE HEALING THROUGH
ENHANCEMENT OF MUSCLE REGENERATION
AND PREVENTION OF FIBROSIS
KENJI SATO, MD,1,2 YONG LI, MD, PhD,1 WILLIAM FOSTER, BS,1
KAZUMASA FUKUSHIMA, MD,1,2 NEIL BADLANI, MS,1 NOBUO ADACHI, MD,1,2
ARVYDAS USAS, MD,1 FREDDIE H. FU, MD,2 and JOHNNY HUARD, PhD1,2
1

Growth and Development Laboratory, Department of Orthopaedic Surgery,
Children’s Hospital and University of Pittsburgh, Pittsburgh, Pennsylvania, USA
2
Department of Orthopaedic Surgery, Division of Sports Medicine, University of Pittsburgh,
Pittsburgh, Pennsylvania, USA
Accepted 24 April 2003

There are various types of muscle injury, including those that occur through direct trauma (e.g., laceration and contusion) and those attributable to indirect damage (e.g., ischemia, denervation, and strain), but the general process of muscle damage and repair is similar in most cases.2,10,12,19 –21,24 –26
Muscle fibers have the ability to regenerate following injury through the activation of satellite cells,13 but the healing process is very slow and often results in incomplete recovery of strength due to the development of scar tissue.12,24,25 The muscle healing
MUSCLE & NERVE

September 2003

FIGURE 2. Quantitative histological analysis of the laceration site by vimentin immunohistochemical staining 4 weeks after injury. Top panels (A), vimentin immunohistochemical stain; lower panel (B), area of scar tissue per field. Control (C), muscles treated with IGF-1
(IG), muscles treated with decorin (D), and muscles treated with both agents (IGϩD); *P Ͻ 0.05.

FIGURE 3. Quantitative analysis of scar tissue by trichrome staining. Scar tissue containing collagen (blue) was analyzed. Top panels, trichrome stain; lower panel, area of scar tissue per field (original magnification ϫ100). Control (C), muscles treated with IGF-1 (IG), muscles treated with decorin (D), and muscles treated with both agents (IGϩD); *P Ͻ 0.05.

Improvement of Muscle Healing

MUSCLE & NERVE

September 2003

369

FIGURE 4. Histogram of physiological evaluation. The strength of the muscle measured ex vivo: (A) tetanus strength; (B) fast-twitch strength. Control (C), normal, nonlacerated muscle (N), muscles treated with IGF-1 (IG), muscles treated with decorin (D), and muscles treated with both agents (IGϩD); *P Ͻ