Human cardiac progenitor cell grafts as unrestricted source of supernumerary cardiac cells in healthy murine hearts.
Human heart harbors a population of resident progenitor cells that can be isolated by stem cell antigen-1 antibody and expanded in culture. These cells can differentiate into cardiomyocytes in vitro and contribute to cardiac regeneration in vivo. However, when directly injected as single cell suspension, less than 1%-5% survive and differentiate. Among the major causes of this failure are the distressing protocols used to culture in vitro and implant progenitor cells into damaged hearts. Human cardiac progenitors obtained from the auricles of patients were cultured as scaffoldless engineered tissues fabricated using temperature-responsive surfaces. In the engineered tissue, progenitor cells established proper three-dimensional intercellular relationships and were embedded in self-produced extracellular matrix preserving their phenotype and multipotency in the absence of significant apoptosis. After engineered tissues were leant on visceral pericardium, a number of cells migrated into the murine myocardium and in the vascular walls, where they integrated in the respective textures. The study demonstrates the suitability of such an approach to deliver stem cells to the myocardium. Interestingly, the successful delivery of cells in murine healthy hearts suggests that myocardium displays a continued cell cupidity that is strictly regulated by the limited release of progenitor cells by the adopted source. When an unregulated cell source is added to the system, cells are delivered to the myocardium. The exploitation of this novel concept may pave the way to the setup of new protocols in cardiac cell therapy.
Laboratorio di Cardiologia Molecolare e Cellulare, Dipartimento di Medicina Interna, Università di Roma Tor Vergata, Roma, Italy.
Giancarlo
G
Forte
Stefano
S
Pietronave
Giorgia
G
Nardone
Andrea
A
Zamperone
Eugenio
E
Magnani
Stefania
S
Pagliari
Francesca
F
Pagliari
Cristina
C
Giacinti
Carmine
C
Nicoletti
Antonio
A
Musaró
Mauro
M
Rinaldi
Marco
M
Ribezzo
Chiara
C
Comoglio
Enrico
E
Traversa
Teruo
T
Okano
Marilena
M
Minieri
Maria
M
Prat
Paolo
P
Di Nardo
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D018920:Coculture Techniques; D005260:Female; D020869:Gene Expression Profiling; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000502:physiology / Q000637:transplantation; D010641:Phenotype; D013234:Stem Cells / Q000166:cytology*; D023822:Tissue Engineering / Q000379:methods*; D016378:Tissue Transplantation / Q000379:methods