Noncultured, autologous, skeletal muscle cells can successfully engraft into ovine myocardium.
BACKGROUND
There is compelling evidence showing that cellular cardiomyoplasty can improve cardiac function. Considering the potential benefit of using noncultured muscle cells (little time, lower cost, reduced risk of contamination), we investigated the feasibility of grafting cells obtained directly after enzymatic dissociation of skeletal muscle biopsies into ovine myocardium. We hypothesized that those noncultured muscle cells would engraft massively.


RESULTS
Autologous, intramyocardial skeletal muscle cell implantation was performed in 8 sheep. A skeletal muscle biopsy sample ( approximately 10 g) was explanted from each animal. The sheep were left to recover for approximately 3 hours and reanesthetized when the cells were ready for implantation. A left fifth intercostal thoracotomy was performed, and 10 epicardial injections of the muscle preparation (between 10 and 20 million cells) were carried out. All sheep were euthanized 3 weeks after myocardial implantation. Immunohistochemistry was performed with monoclonal antibodies to a fast skeletal isoform of myosin heavy chain. Skeletal myosin heavy-chain expression was detected in all slides at 3 weeks after implantation in 8 of 8 animals, confirming engraftment of skeletal muscle cells. Massive areas of engraftment (from 2 to 9 mm in diameter) or discrete loci were noted within the myocardial wall.


CONCLUSIONS
Our results indicate that noncultured skeletal muscle cells can successfully and massively engraft in ovine myocardium. Thus, avoiding the cell culture expansion phase is feasible and could become a promising option for cellular cardiomyoplasty.
Borenstein
Nicolas
N
IMM Recherche, Institut Mutualiste Montosuris, 75014 Paris, France. cera@imm.fr
Bruneval
Patrick
P
Hekmati
Mehrak
M
Bovin
Christophe
C
Behr
Luc
L
Pinset
Christian
C
Laborde
François
F
Montarras
Didier
D
D000818:Animals; D002469:Cell Separation; D002478:Cells, Cultured; D005240:Feasibility Studies; D006085:Graft Survival / Q000502:physiology*; D007150:Immunohistochemistry; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation*; D017570:MyoD Protein / Q000096:biosynthesis; D009206:Myocardium / Q000166:cytology*; D018995:Myosin Heavy Chains / Q000096:biosynthesis; D012756:Sheep; D014182:Transplantation, Autologous
D017570:MyoD Protein; D018995:Myosin Heavy Chains