Darren Freed ( MD, University of Alberta; PhD, University of Manitoba)
Department of Surgery, Division of Cardiac Surgery
University of Alberta
2D4.34 WMC, 8440-112 Street
University of Alberta Hospital
Edmonton, Alberta, Canada, T6G 2B7
Tel: 780 407-1959
Fax: 780 407-3672
Cardiac transplantation is the gold standard therapy for the treatment of end-stage heart failure refractory to medical therapies. However the wider application of this life saving intervention is limited by the availability of donor organs. Ex vivo organ perfusion has been proposed as a method to expand the pool of donor organs for transplantation. My lab is developing a device that allows full biventricular working mode analysis of donor cardiac function. Experiments are ongoing to determine the optimal conditions for ex vivo myocardial perfusion and techniques to maximize the time the heart can be maintained in a beating state outside the body. The application of this approach is being investigated in a large animal model of heart transplantation.
The other major theme of research in my laboratory has been myocardial fibrosis and wound healing, with particular emphasis on the role of progenitor cells. We have found that human bone marrow stem cells (MSC) and human ventricular myofibroblasts have significant similarity with respect to phenotype and function. Furthermore, we also isolated ventricular fibroblasts from discarded ventricular tissue from patients undergoing ventricular assist device placement. Comparing the two human cell types, we showed that human MSC respond to transforming growth factor-beta in similar fashion to human ventricular fibroblasts with respect to collagen synthesis and collagen gel contraction. We have also identified a novel microRNA, as a regulator of the MSC myogenic phenotype. Through these experiments we have identified a potential therapeutic target for treating or possibly preventing fibrosis.
- Karlstedt E, Jassal DS, Kirkpatrick IDC, Freed DH, Seifer CM. Multimodality cardiac imaging of infective endocarditis. J Cardiovasc Med. 2014 Jul 10. [Epub ahead of print].
- Menard CE, Durston M, Zherebitskaya E, Smith DR, Freed DH, Tian G, Fernyhough P, Arora RC. Temporal Dystrophic Remodeling within the Intrinsic Cardiac Nervous System of the Streptozotocin-Induced Diabetic Rat Model. Acta Neuropath Comm. 2014 Jun 4;2(1):60. [Epub ahead of print].
- Ghavami S, Gupta S, Hauch EA, Hnatowich M, Freed DH, Dixon IMC. Autophagy and Heart Disease: Implications for Ischemia/Reperfusion Damage. Curr Mol Med. 2014 Jun 2. [Epub ahead of print].
- Liu S, Horne D, Freed DH, Sookhoo S, Strzelczyk J, Ravandi A, Jassal DS. Multimodality Imaging of a Cardiac Pheochromocytoma. J Am Coll Cardiol. 2014 Apr 12. pii:S0735-1097(14)02011-7.
- Santiago JJ, McNaughton LJ, Ma X, Nickel BE, Fandrich RR, Freed DH, Arora RC, Kardami E. High molecular weight fibroblast growth factor-2 in the human heart is a potential target for prevention of cardiac remodelling. PLOS ONE. 2014 May 14;9(5):e97281.
- Wang J, Xiang B, Lin HY, Liu H, Freed D, Arora RC, Tian G. Pathological mechanism for delayed hyperenhancement of chronic scarred myocardium in contrast agent enhanced magnetic resonance imaging. PLOS ONE. 2014 May 6;9(5):e96463.
- Ngo MA, Li Y, Neumann S, Durston M, Tian G, Dixon IMC, Arora RC, Freed DH. Human Mesenchymal Stem Cells Adopt a Myofibroblastic Phenotype in vitro: comparison to human cardiac myofibroblasts. Mol Cell Biochem. 2014 Jul; 392(1-2): 187-204.