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PRECLINICAL STUDY

Recipient Age Determines the Cardiac Functional Improvement Achieved by Skeletal Myoblast Transplantation

Chung-Dann Kan, MD^_*,, Shu-Hong Li, MSc^_*, Richard D. Weisel, MD^_*, Shun Zhang, BSc^_* and Ren-Ke Li, MD, PhD^_*,_*

^_* Division of Cardiovascular Surgery, Toronto General Research Institute, University of Toronto, Toronto, Ontario, Canada
Department of Surgery, National Cheng Kung University Hospital Institute of Clinical Medicine, Cardiovascular Research Center, Medical College, National Cheng Kung University, Taiwan, Republic of China

Manuscript received March 20, 2007; revised manuscript received June 4, 2007, accepted June 5, 2007.

^_* Reprint requests and correspondence: Dr. Ren-Ke Li, MaRS Centre, Toronto Medical Discovery Tower, 3rd Floor, Room 702, 101 College Street, Toronto, Ontario, Canada M5G 1L7. (Email: RenKeLi{at}uhnres.utoronto.ca).

Objectives: The aim of the current study was to evaluate the effect of recipient age on the regenerative response to implantation with young skeletal myoblasts (SKMCs) after a coronary artery ligation.

Background: In contrast with previous findings in animals, the initial clinical trials of cell transplantation after a myocardial infarction have reported only limited improvements in ventricular function. The restricted regenerative capacity of cells isolated from older patients is certainly a factor; however, the present study investigated the impact of another potentially significant factor: recipient age.

Methods: We compared the myogeneic capacities of SKMCs isolated from young rats (3 months old) and older rats (24 months old). Highly myogenic SKMCs derived from young rats (or culture media, in control rats) were then transplanted into the infarcted myocardium of young and older recipients at 1 week after coronary ligation.

Results: In vitro, proliferation and myotube formation were significantly greater in SKMCs derived from young rats than from older rats. In vivo, young and older recipients of SKMCs exhibited increases in cell density, vascular density, and collagen preservation relative to age-matched control animals. However, cell therapy produced significantly greater functional improvements in young recipients than in older, along with relative increases in stem cell factor, cell density, cell survival, and angiogenesis.

Conclusions: Functional improvement after the post–myocardial infarction implantation of young SKMCs was limited in older recipients, likely due to reductions in their cardiac and systemic responses to cell transplantation.

Abbreviations and Acronyms   EF = ejection fraction   FAC = fractional area change   FS = fractional shortening   MHC = myosin heavy chain   MI = myocardial infarction   SCF = stem cell factor   SKMC = skeletal myoblast

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