Published online before print February 5, 2007, doi: 10.1161/CIRCULATIONAHA.106.655209
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2007;115:896-908.)
© 2007 American Heart Association, Inc.
Molecular Cardiology |
Regenerative Potential of Cardiosphere-Derived Cells Expanded From Percutaneous Endomyocardial Biopsy Specimens
From the Division of Cardiology (R.R.S., L.B., H.C.C., M.K.L., J.M.H., E. Messina, M.R.A., E. Marbán), Johns Hopkins University, Baltimore, Md, and Department of Experimental Medicine, Pasteur Institute, Cenci Bolognetti Foundation, University La Sapienza, Rome, Italy (L.B., E. Messina, A.G.).
Correspondence to Eduardo Marbán, MD, 720 Rutland Ave, Ross 858, Baltimore, MD 21205. E-mail marban{at}jhmi.edu
Received July 28, 2006; accepted November 27, 2006.
Background— Ex vivo expansion of resident cardiac stem cells, followed by delivery to the heart, may favor regeneration and functional improvement.
Methods and Results— Percutaneous endomyocardial biopsy specimens grown in primary culture developed multicellular clusters known as cardiospheres, which were plated to yield cardiosphere-derived cells (CDCs). CDCs from human biopsy specimens and from comparable porcine samples were examined in vitro for biophysical and cytochemical evidence of cardiogenic differentiation. In addition, human CDCs were injected into the border zone of acute myocardial infarcts in immunodeficient mice. Biopsy specimens from 69 of 70 patients yielded cardiosphere-forming cells. Cardiospheres and CDCs expressed antigenic characteristics of stem cells at each stage of processing, as well as proteins vital for cardiac contractile and electrical function. Human and porcine CDCs cocultured with neonatal rat ventricular myocytes exhibited biophysical signatures characteristic of myocytes, including calcium transients synchronous with those of neighboring myocytes. Human CDCs injected into the border zone of myocardial infarcts engrafted and migrated into the infarct zone. After 20 days, the percentage of viable myocardium within the infarct zone was greater in the CDC-treated group than in the fibroblast-treated control group; likewise, left ventricular ejection fraction was higher in the CDC-treated group.
Conclusions— A method is presented for the isolation of adult human stem cells from endomyocardial biopsy specimens. CDCs are cardiogenic in vitro; they promote cardiac regeneration and improve heart function in a mouse infarct model, which provides motivation for further development for therapeutic applications in patients.
CLINICAL PERSPECTIVE
This article has been cited by other articles:
 |
|
 |
|
  H. Kubo, N. Jaleel, A. Kumarapeli, R. M. Berretta, G. Bratinov, X. Shan, H. Wang, S. R. Houser, and K. B. Margulies Increased Cardiac Myocyte Progenitors in Failing Human Hearts Circulation, August 5, 2008; 118(6): 649 - 657. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Dimmeler and A. Leri Aging and Disease as Modifiers of Efficacy of Cell Therapy Circ. Res., June 6, 2008; 102(11): 1319 - 1330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Smart and P. R. Riley The Stem Cell Movement Circ. Res., May 23, 2008; 102(10): 1155 - 1168. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Terrovitis, M. Stuber, A. Youssef, S. Preece, M. Leppo, E. Kizana, M. Schar, G. Gerstenblith, R. G. Weiss, E. Marban, et al. Magnetic Resonance Imaging Overestimates Ferumoxide-Labeled Stem Cell Survival After Transplantation in the Heart Circulation, March 25, 2008; 117(12): 1555 - 1562. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Pouly, P. Bruneval, C. Mandet, S. Proksch, S. Peyrard, C. Amrein, V. Bousseaux, R. Guillemain, A. Deloche, J.-N. Fabiani, et al. Cardiac stem cells in the real world J. Thorac. Cardiovasc. Surg., March 1, 2008; 135(3): 673 - 678. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Dimmeler, J. Burchfield, and A. M. Zeiher Cell-Based Therapy of Myocardial Infarction Arterioscler. Thromb. Vasc. Biol., February 1, 2008; 28(2): 208 - 216. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Limana, A. Zacheo, D. Mocini, A. Mangoni, G. Borsellino, A. Diamantini, R. De Mori, L. Battistini, E. Vigna, M. Santini, et al. Identification of Myocardial and Vascular Precursor Cells in Human and Mouse Epicardium Circ. Res., December 7, 2007; 101(12): 1255 - 1265. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. N. Ebert, D. G. Taylor, H.-L. Nguyen, D. P. Kodack, R. J. Beyers, Y. Xu, Z. Yang, and B. A. French Noninvasive Tracking of Cardiac Embryonic Stem Cells In Vivo Using Magnetic Resonance Imaging Techniques Stem Cells, November 1, 2007; 25(11): 2936 - 2944. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Pijnappels, J. van Tuyn, A. A.F. de Vries, R. W. Grauss, A. van der Laarse, D. L. Ypey, D. E. Atsma, and M. J. Schalij Resynchronization of Separated Rat Cardiomyocyte Fields With Genetically Modified Human Ventricular Scar Fibroblasts Circulation, October 30, 2007; 116(18): 2018 - 2028. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Kehat and L. Gepstein Electrophysiological Coupling of Transplanted Cardiomyocytes Circ. Res., August 31, 2007; 101(5): 433 - 435. [Full Text] [PDF]
|
|
|
|
|
|
K. R. Sipido and S. P. Janssens How Old Is Your Heart? Circ. Res., August 17, 2007; 101(4): 323 - 325. [Full Text] [PDF]
|
|
|
|
|
|
E. Marban Big Cells, Little Cells, Stem Cells: Agents of Cardiac Plasticity Circ. Res., March 2, 2007; 100(4): 445 - 446. [Full Text] [PDF]
|
|