Cardiovascular Research

Cardiomyocyte transplantation into the failing heart-new therapeutic approach for heart failure?

Authors: Thorsten Reffelmann|||Jonathan Leor|||Jochen Müller-Ehmsen|||Larry Kedes|||Robert A Kloner

Affiliations: + Expand

Abstract

Heart failure, frequently the consequence of irreversible myocardial damage with subsequent formation of akinetic scar tissue, is a highly prevalent disease, and in its advanced stages associated with high mortality. The transplantation of exogenous cells with the inherent ability to contract has been put forward as one potential treatment strategy to increase contractility and cardiac performance. Besides skeletal myoblasts or stem cells from various sources, immature cardiomyocytes, such as fetal or neonatal cardiomyocytes, have been transplanted into normal, cryoinjured, infarcted myocardium, as well as into models of global heart failure. Survival of transplanted immature cardiomyocytes has been demonstrated up to 6-7 months, accompanied by vascularization of the grafted tissue. Transplants developed sarcomeric structures and other morphological features of differentiation. The principal possibility of cell-to-cell coupling between graft and host cells was demonstrated after cardiomyocyte transplantation into normal hearts and in some studies in damaged myocardium. But most long-term follow-up investigations in models of myocardial infarction reported that optimal integration of the engrafted cells appeared to be hindered by scar tissue, separating the transplant from the host. Nonetheless, in several studies, improved parameters of cardiac performance were demonstrated ex-vivo and in vivo. Potential mechanisms might involve beneficial effects on the remodeling process. In this review, we critically evaluate the potential value of cardiomyocyte transplantation as a new approach in the treatment of the syndrome of "heart failure".

---

Reference List

J Am Coll Cardiol. 1992 Jul;20(1):248-54|||In Vitro Cell Dev Biol Anim. 1995 Mar;31(3):190-5|||J Muscle Res Cell Motil. 1997 Feb;18(1):63-70|||Circulation. 1996 Sep 15;94(6):1394-401|||J Intern Med. 1995 Feb;237(2):135-41|||Circ Res. 1999 Aug 6;85(3):294-301|||Circulation. 2002 Apr 9;105(14):1720-6|||J Clin Invest. 1995 Jan;95(1):114-21|||Nat Med. 1998 Aug;4(8):929-33|||Dev Biol. 1994 Mar;162(1):9-17|||Circ Res. 1996 Apr;78(4):547-52|||Circ Res. 1996 Feb;78(2):283-8|||Circulation. 1997 Nov 4;96(9 Suppl):II-188-93|||Pediatr Res. 1988 Jun;23(6):637-42|||J Mol Cell Cardiol. 1996 Oct;28(10):2057-67|||J Interv Cardiol. 1995 Aug;8(4):387-93|||Cell Transplant. 1998 May-Jun;7(3):239-46|||Circulation. 1998 Nov 10;98 (19 Suppl):II151-5; discussion II155-6|||Ann Thorac Surg. 1999 Jan;67(1):124-9|||N Engl J Med. 1996 May 23;334(21):1349-55|||Ann Thorac Surg. 1996 Sep;62(3):654-60; discussion 660-1|||J Thorac Cardiovasc Surg. 2000 Jun;119(6):1169-75|||Circulation. 2000 Nov 7;102(19 Suppl 3):III359-64|||Am Heart J. 1991 Mar;121(3 Pt 1):951-7|||Science. 1997 Apr 4;276(5309):71-4|||Circulation. 1999 Aug 31;100(9):999-1008|||N Engl J Med. 1991 Nov 21;325(21):1468-75|||World J Surg. 2000 Jul;24(7):811-4|||Transplant Proc. 1997 Jun;29(4):2093-4|||FASEB J. 2000 Dec;14(15):2540-8|||J Mol Cell Cardiol. 2001 Jul;33(7):1321-30|||J Thorac Cardiovasc Surg. 1999 Oct;118(4):715-24|||Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8801-5|||J Mol Cell Cardiol. 1996 Aug;28(8):1737-46|||Eur Heart J. 1983 Jul;4(7):445-8|||Circulation. 1995 May 15;91(10 ):2504-7|||Proc Assoc Am Physicians. 1997 May;109(3):245-53|||Lancet. 2001 Jan 27;357(9252):279-80|||Circulation. 1999 Nov 9;100(19 Suppl):II247-56|||Arch Mal Coeur Vaiss. 2001 Mar;94(3):180-2|||J Clin Invest. 1999 Mar;103(5):697-705|||Circulation. 2001 Sep 18;104(12 Suppl 1):I218-22|||Circ Res. 1990 Jan;66(1):84-102|||Am J Physiol. 1993 May;264(5 Pt 2):H1727-33|||N Engl J Med. 1999 Sep 2;341(10):709-17|||J Clin Invest. 1995 Oct;96(4):2034-42|||Circulation. 1996 Nov 1;94(9 Suppl):II332-6|||J Mol Cell Cardiol. 2002 Feb;34(2):107-16|||Circulation. 2000 Nov 7;102(19 Suppl 3):III204-9|||Circulation. 2001 Apr 10;103(14):1920-7|||N Engl J Med. 2001 Jun 7;344(23):1750-7|||Mech Dev. 1993 Nov;44(1):41-50|||Nature. 2001 Apr 5;410(6829):701-5|||J Clin Invest. 1993 Sep;92(3):1115-6|||Circulation. 1999 Nov 9;100(19 Suppl):II262-8|||Science. 1999 Apr 2;284(5411):143-7|||Science. 1994 Apr 1;264(5155):98-101|||Curr Biol. 2001 Jun 5;11(11):855-8|||J Clin Invest. 1996 Dec 1;98(11):2512-23|||J Am Geriatr Soc. 1997 Aug;45(8):968-74|||N Engl J Med. 1991 Aug 1;325(5):293-302|||Ann Thorac Surg. 2001 Dec;72(6):1957-63|||Dtsch Med Wochenschr. 2001 Aug 24;126(34-35):932-8|||J Mol Cell Cardiol. 2001 May;33(5):907-21|||Circulation. 1997 Nov 4;96(9 Suppl):II-179-86; discussion 186-7|||Circulation. 1999 Jul 13;100(2):193-202|||J Cell Sci. 2000 Jan;113 ( Pt 1):5-10|||Circulation. 1996 Nov 1;94(9 Suppl):II337-40|||Am J Pathol. 1992 Jul;141(1):183-91