Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans. Histological analysis of cell survival and differentiation.
OBJECTIVE
We report histological analysis of hearts from patients with end-stage heart disease who were transplanted with autologous skeletal myoblasts concurrent with left ventricular assist device (LVAD) implantation.


BACKGROUND
Autologous skeletal myoblast transplantation is under investigation as a means to repair infarcted myocardium. To date, there is only indirect evidence to suggest survival of skeletal muscle in humans.


METHODS
Five patients (all male; median age 60 years) with ischemic cardiomyopathy, refractory heart failure, and listed for heart transplantation underwent muscle biopsy from the quadriceps muscle. The muscle specimen was shipped to a cell isolation facility where myoblasts were isolated and grown. Patients received a transplant of 300 million cells concomitant with LVAD implantation. Four patients underwent LVAD explant after 68, 91, 141, and 191 days of LVAD support (three transplant, one LVAD death), respectively. One patient remains alive on LVAD support awaiting heart transplantation.


RESULTS
Skeletal muscle cell survival and differentiation into mature myofibers were directly demonstrated in scarred myocardium from three of the four explanted hearts using an antibody against skeletal muscle-specific myosin heavy chain. An increase in small vessel formation was observed in one of three patients at the site of surviving myotubes, but not in adjacent tissue devoid of engrafted cells.


CONCLUSIONS
These findings represent demonstration of autologous myoblast cell survival in human heart. The implanted skeletal myoblasts formed viable grafts in heavily scarred human myocardial tissue. These results establish the feasibility of myoblast transplants for myocardial repair in humans.
Pagani
Francis D
FD
Section of Cardiac Surgery, University of Michigan, Ann Arbor, MI 48109, USA. fpagani@umich.edu
DerSimonian
Harout
H
Zawadzka
Agatha
A
Wetzel
Kristie
K
Edge
Albert S B
AS
Jacoby
Douglas B
DB
Dinsmore
Jonathan H
JH
Wright
Susan
S
Aretz
Tom H
TH
Eisen
Howard J
HJ
Aaronson
Keith D
KD
D000368:Aged; D001707:Biopsy, Needle; D002470:Cell Survival; D017690:Cell Transplantation / Q000379:methods; D003131:Combined Modality Therapy; D005500:Follow-Up Studies; D006085:Graft Survival; D006353:Heart-Assist Devices; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D032448:Myoblasts, Skeletal / Q000473:pathology* / Q000637:transplantation*; D017202:Myocardial Ischemia / Q000150:complications / Q000401:mortality / Q000473:pathology* / Q000601:surgery*; D011336:Probability; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D015996:Survival Rate; D014182:Transplantation, Autologous; D016896:Treatment Outcome