Author + information
- Valeri Chekanov, MD, PhD⁎ (, )
- Nicholas Kipshidze, MD, PhD and
- Victor Nikolaychik, MD, PhD
- ↵⁎Aurora Sinai/St. Luke’s Medical Centers, University of Wisconsin, 945 N. 12th Street, Room W301, PO Box 342, Milwaukee, WI 53201-0342
The recent study by Christman et al. (1) reports the results of an experimental study that evaluated a “novel approach to heart repair that uses an injectable biopolymer scaffold to deliver cells directly into the infarct wall.” The researchers “hypothesized that the injection of cells in a solution that becomes a semi-rigid scaffold upon injection would increase cell transplant retention and survival within the infarct, compared with the standard injection technique.”
The investigators failed to acknowledge that this theory was presented by our group at the American Heart Association meetings in 2001 and the American College of Cardiology meetings in 2002 and 2003. Neither do they reference our published works (both experimental and clinical) evaluating the role of fibrin matrices as a scaffold for cell transplantation and as an angiogenic agent. Using transmission electron microscopy, we discovered that fibrin platform directs the morphofunctional process of capillary formation and accelerates neovascularization in ischemic myocardium in addition to enhancing the viability of transplanted endothelial cells (2,3).
We documented improvement in left ventricular ejection fraction, myocardial blood, and capillary density.
We avoided the possibility of higher graft rejection from using an inbred strain and allograft transplantation, the limitation the investigators mention, by employing autologous endothelial cells and autologous fibrinogen for fibrin sealant preparation. Endothelial cells (ECs) were cultivated from endothelium of the jugular veins of the same sheep (3). One week before EC transplantation, whole blood from each animal was collected, and a standard cryoprecipitate technique was used to prepare autologous fibrinogen from sheep plasma. Cultured in a two-dimensional fibrin matrix, ECs quickly formed a cobblestone monolayer that had a density 2- to 2.5-fold higher than in controls cultivated on a single-plane tissue culture surface (4). We also found that, cultured in a three-dimensional fibrin matrix, ECs formed true capillaries, while other vascular cells trapped in this matrix underwent apoptosis.
In our next investigation, we found that a fibrin-based sealant becomes vascularized when placed between two ischemic tissues and that aprotinin, added to fibrinogen, considerably increased the process of neovascularization (5). Fibrin-based sealant proved capable of delivering plasma proteins necessary to perform the functions of an extracellular matrix, anchoring ECs to the vessel wall (6).
Finally, we demonstrated that fibrin-based sealant accelerates angiogenesis in patients with peripheral artery disease (7).
We thank Christman et al. (1) for their interesting contribution on this subject and applaud the renewed interest in this worthy line of inquiry. With further preclinical and clinical investigation of the safety and efficacy of this technique, we believe that fibrin matrix as a scaffold for cell therapy, and the angiogenic potential of fibrin compositions, show promise for the treatment of heart disease.
- American College of Cardiology Foundation
- Christman K.L.,
- Vardanian A.J.,
- Sievers R.E.,
- Fang Q.,
- Fok H.H.,
- Lee R.J.
- Chekanov V.S.,
- Nikolaychik V.V.,
- Rieder M.A.,
- Tchekanov G.V.
- Kipshidze N.,
- Fergusson J.J. III.,
- Keelan M.H. Jr..,
- et al.