Cell Transplantation for Myocardial Repair: An Experimental Approach

Abstract

Myocardium lacks the ability to regenerate following injury. This is in contrast to skeletal muscle (SKM), in which capacity for tissue repair is attributed to the presence of satellite cells. It was hypothesized that SKM satellite cells multiplied in vitro could be used to repair injured heart muscle. Fourteen dogs underwent explantation of the anterior tibialis muscle. Satellite cells were multiplied in vitro and their nuclei were labeled with tritiated thymidine 24 h prior to implantation. The same dogs were then subjected successfully to a myocardial injury by the application of a cryoprobe. The cells were suspended in serum-free growth medium and autotransplanted within the damaged muscle. Medium without cells was injected into an adjacent site to serve as a control. Endpoints comprised histology using standard stains as well as Masson trichrome (specific for connective tissue), and radioautography. In five dogs, satellite cell isolation, culture, and implantation were technically satisfactory. In three implanted dogs, specimens were taken within 6-8 wk. There were persistence of the implantation channels in the experimental sites when compared to the controls. Macroscopically, muscle tissue completely surrounded by scar tissue could be seen. Masson trichrome staining showed homogeneous scar in the control site, but not in the test site where a patch of muscle fibres containing intercalated discs (characteristic of myocardial tissue) was observed. In two other dogs, specimens were taken at 14 wk postimplantation. Muscle tissue could not be found. These preliminary results could be consistent with the hypothesis that SKM satellite cells can form neo-myocardium within an appropriate environment. Our specimens failed to demonstrate the presence of myocyte nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

Systemic Delivery of Allogenic Muscle Stem Cells Induces Long-Term Muscle Repair and Clinical Efficacy in Duchenne Muscular Dystrophy Dogs

“…51,52 Cells were placed in a growth medium [44% DMEM (VWR, Strasbourg, France), 44% M199 (VWR), 10% fetal calf serum (Sigma, St. Louis, MO), 1% penicillin/streptomycin/fungizon (Sigma), and 1% L-glutamine (Sigma)], seeded at 10 5 cells/cm 2 on gelatin-coated flasks (Sigma), and submitted to an adaptation of the preplating technique. 30 After 1 hour, floating cells were collected and replated on new flasks for 24 hours.…”

Systems approaches to preventing transplanted cell death in cardiac repair

“…Many strategies being pursued to restore heart function involve repopulating the heart with exogenously delivered cells, either by direct injection [1,2] or intravascular delivery. The first attempts to repopulate the scarred aftermath of myocardial infarction (MI) were performed over fifteen years ago [3][4][5]. Since that time, interest in cell transplantation for the prevention and treatment of heart failure has exploded, leading to multiple animal studies and clinical trials [2].…”

Comparison of Intracardiac Cell Transplantation: Autologous Skeletal Myoblasts Versus Bone Marrow Cells

“…Myoblasts engraft, 6 differentiate toward a phenotype adapted to cardiac workload, 7 and improve heart function. 1,8 Bone marrow progenitor cells are reported to have the capacity to differentiate into cardiomyocytes both in vitro 9 and in vivo, 5 and improve global heart function preclinically.…”