Introduction

Theregen's product development program for Anginera is based on Dermagraft, an FDA-approved, cell-based wound management product. The Anginera technology platform applies a solid foundation of proven research into the cardiovascular arena. Backed by compelling animal data in several heart models, Theregen scientists have advanced into clinical studies in the human heart.

Anginera Technology Summary

Anginera Animal Studies - Mouse Infarct Model Summary

Theregen conducted several small and large animal pre-clinical studies to support its Investigational New Drug (IND) application in 2005 to the U.S. Food and Drug Administration.

The company's mouse heart infarct study results (summary below) provided convincing evidence that our researchers should move to larger animal model studies to confirm the product's safety and effectiveness at the pre-clinical level.

Title: Efficacy Study of Anginera for Use as a Cardiac Treatment in a Mouse Model of Myocardial Ischemia

Results:

  • Anginera stimulated mature blood vessel formation (Circulation, Oct. 23, 2001)
  • Anginera prevented loss of left ventricular function after an immediate infarct. Survival, post-infarct, was substantially enhanced along with ejection fraction values (Tissue Engineering, Kellar, RS, et al., in press)

Anginera Animal Studies - Canine Safety (GLP) Study

A canine safety study, designed with the advice of the U.S. FDA, was conducted in 2003-04 in preparation for Theregen's IND submission to the Agency.

Title: Safety Study of Anginera for Use as a Cardiac Treatment in a Canine Model of Myocardial Ischemia

Results:

  • Evidence of efficacy demonstrated by echocardiography at both time points and dosing levels

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Anginera Clinical Research

Clinical Applications

Initially, the safety of Anginera will be studied in patients with diffuse coronary artery disease and ischemic myocardial tissue. The product will be studied as an adjunct treatment to CABG (coronary artery bypass grafting) surgery.

Pending results of the human safety study and further animal testing, the target for human efficacy studies may be one or both of the following:

  • Adjunct to CABG in patients with reversible myocardial ischemia
  • Patients with congestive heart failure symptoms. These symptoms include wall thinning, reduced ventricular wall function and ejection fractions.

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Glossary of Terms

Publications

Anginera Angiogenesis Research

Kellar RS, Shepherd BR, Larson DF, Naughton G, Williams SK. Cardiac Patch Constructed from Human Fibroblasts Attenuates Reduction in Cardiac Function after Acute Infarct. Accepted for publication in Tissue Engineering, 2006.

Roberts C, Ratcliffe A, Mansbridge J, Kellar RS. Tissue Engineering for Tissue and Organ Repair: Angiogenesis as a Mechanism of Action. Recent Research Developments in Biomaterials. 323-334. 2002.

Kellar RS, Landeen LK, Shepherd BR, Naughton GK, Ratcliffe A, Williams SK. Scaffold-Based, Three-Dimensional, Human Fibroblast Culture Provides a Structural Matrix That Supports Angiogenesis in Infarcted Heart Tissue. Circulation, 2001; 104:2063-2068.

Dermagraft Studies

Gentzkow GD. Dermagraft: living bioengineered, human dermis for healing chronic wounds. In The Wound Management Manual, Bok Y. Lee, editor. McGraw-Hill, New York, 2005

Gentzkow, G, Jensen J, Pollak R, et al. Improved healing of diabetic foot ulcers after grafting with a living human dermal replacement. Wounds,11(3):77-84, 1999

Pollak RA, Edington H, Jensen JL, Kroeker RO, Gentzkow GD. A human dermal replacement for the treatment of diabetic foot ulcers. Wounds, 9(6):175-183, 1997

Naughton G, Mansbridge J, Gentzkow G. A Metabolically Active Human Dermal Replacement for the Treatment of Diabetic Foot Ulcers. Artificial Organs, 21(11):1203-1210, 1997

Gentzkow GD, Iwasaki I, Hershon KS, et al. Use of Dermagraft, a Cultured Human Dermis, to Treat Diabetic Foot Ulcers. Diabetes Care, 19(4):350-354, 1996

Omar AA, Mavor AI, Jones AM, Homer-Vanniasinkam S. Treatment of venous leg ulcers with Dermagraft. Eur. J. Vasc Endovasc Surg., 2004 Jun;27(6):666-72.

Marston WA, Hanft J, Norwood P, Pollak R; Dermagraft Diabetic Foot Ulcer Study Group. The efficacy and safety of Dermagraft in improving the healing of chronic diabetic foot ulcers: results of a prospective randomized trial. Diabetes Care,. 2003 Jun;26(6):1701-5.

Newton DJ, Khan F, Belch JJ, Mitchell MR, Leese GP. Blood flow changes in diabetic foot ulcers treated with dermal replacement therapy. J. Foot Ankle Surg., 2002 Jul-Aug;41(4):233-7.

Pinney E, Liu K, Sheeman B, Mansbridge J. Human three-dimensional fibroblast cultures express angiogenic activity. J Cell Physiol., 2000; 183(1):74-82.

Naughton GK, Mansbridge JN. Human-based tissue-engineered implants for plastic and reconstructive surgery. Clin Plast Surg. 1999 Oct;26(4):579-86, viii.

Mansbridge JN, Liu K, Pinney RE, Patch R, Ratcliffe A, Naughton GK. Growth factors secreted by fibroblasts: role in healing diabetic foot ulcers. Diabetes Obes Metab. 1999 Sep;1(5):265-79.

Mansbridge J, Liu K, Pinney E, Patch R, Ratcliffe A, Naughton G. Growth factors secreted by fibroblasts: role in healing diabetic foot ulcers. Diabetes, Obesity and Metabolism, 1999; 1:265-279.

Jiang WG, Harding KG. Enhancement of wound tissue expansion and angiogenesis by matrix-embedded fibroblast (dermagraft), a role of hepatocyte growth factor/scatter factor. Int J Mol Med, 1998; 2(2):203-210.

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Related Animal Studies (in cardiac models)

Horvath KA, Lu CY, Robert E, Pierce GF, Greene R, Sosnowski BA, Doukas J. Improvement of myocardial contractility in a porcine model of chronic ischemia using a combined transmyocardial revascularization and gene therapy approach. J Thorac Cardiovasc Surg., 2005 May;129(5):1071-7.

Yamaguchi T, Sawa Y, Miyamoto Y, Takahashi T, Jau CC, Ahmet I, Nakamura T, Matsuda H. Therapeutic angiogenesis induced by injecting hepatocyte growth factor in ischemic canine hearts. Surg Today, 2005;35(10):855-60.

Almeda FQ, Glock D, Sandelski J, Ibrahim O, Macioch JE, Allen T, Dainauskas JR, Parrillo JE, Snell RJ, Schaer GL. The effect of percutaneous transmyocardial laser revascularization on left ventricular function in a porcine model of hibernating myocardium A pilot study. Cardiovasc Radiat Med., 2004 Jul-Sep;5(3):132-5.

Li W, Chiba Y, Kimura T, Morioka K, Uesaka T, Ihaya A, Muraoka R. Transmyocardial laser revascularization induced angiogenesis correlated with the expression of matrix metalloproteinases and platelet-derived endothelial cell growth factor. Eur J Cardiothorac Surg., 2001; 19(2):156-163.

Unger EF. Experimental evaluation of coronary collateral development. Cardiovascular Research, 2001; 49:497-506.

Schaper W. Therapeutic arteriogenesis has arrived. Circulation, 2001; 104(17):1994-1995.

Roethy W, Fiehn E, Suehiro K, Gu A, Yi GH, Shimizu J, Wang J, Zhang G, Ranieri J, Akella R, Funk SE, Sage EH, Benedict J, Burkhoff D. A growth factor mixture that significantly enhances angiogenesis in vivo. J Pharmacol Exp Ther, 2001; 299(2):494-500.

Yamamoto N, Kohmoto T, Roethy W, Gu A, DeRosa C, Rabbani LE, Smith CR, Burkhoff D. Histological evidence that basic fibroblast growth factor enhances the angiogenic effects of transmyocardial laser revascularization. Basic Res Cardiol, 2000; 95:55-63.

Rajanayagam MA, Shou M, Thirumurti V, Lazarous DF, Quyyumi AA, Goncalves L, Stiber J, Epstein SE, Unger EF. Intracoronary basic fibroblast growth factor enhances myocardial perfusion in dogs. J Am Coll Cardiol, 2000; 35:519-526.

Horvath KA, Chiu E, Maun DC, Lomasney JW, Greene R, Pearce WH, Fullerton DA. Up-regulation of vascular endothelial growth factor mRNA and angiogenesis after transmyocardial laser revascularization. Ann Thorac Surg., 1999; 68:825-829.

Chu VF, Kuang JQ, McGinn AN, Giaid A, Korkola S, Chiu RC. Angiogenic response induced by mechanical transmyocardial revascularization. J Thorac Cardiovasc Surg., 1999; 118(849):856.

Lazarous DF, Shou M, Stiber JA, Hodge E, Thirumurti V, Goncalves L, Unger EF. Adenoviral-mediated gene transfer induces sustained pericardial VEGF expression in dogs: effect on myocardial angiogenesis. Cardiovasc Res., 1999; 44(2):294-302.

Laham RJ, Simons M, Tofukuji M, Hung D, Sellke FW. Modulation of myocardial perfusion and vascular reactivity by pericardial basic fibroblast growth factor: insight into ischemia-induced reduction in endothelium-dependent vasodilatation. J Thorac Cardiovasc Surg., 1998; 116(6):1022-1028.

Lutter G, Yoshitake M, Takahashi N, Nitzsche E, Martin, J, Sarai K, Lutz C, Beyersdorf F. Transmyocardial laser-revascularization: experimental studies on prolonged acute regional ischemia. European Journal of Cardio-Thoracic Surgery, 1998; 13(6):694-701.

Burkhoff D, Fulton R, Wharton K, Rizzuto C, Billingham ME, Robbins RC: Myocardial perfusion through naturally occurring subendocardial channels. J Thorac Cardiovasc Surg., 1997; 114:497-99.

Lopez JJ, Edelman ER, Stamler A, Hibberd MG, Prasad P, Caputo RP, Carrozza JP, Douglas PS, Sellke FW, Simons M. Basic fibroblast growth factor in a porcine model of chronic myocardial ischemia: a comparison of angiographic, echocardiographic and coronary flow parameters. Journal of Pharmacology & Experimental Therapeutics, 1997; 282(1):385-390.

Hariawala MD, Horowitz JR, Esakof D, Sheriff DD, Walter DH, Keyt B, Isner JM, Symes JF. VEGF improves myocardial blood flow but produces EDRF-mediated hypotension in porcine hearts. Journal of Surgical Research, 1996; 63(1):77-82.

Unger EF, Banai S, Shou M, Lazarous DF, Jaklitsch MT, Scheinowitz M, Correa R, Klingbeil C, Epstein SE. Basic fibroblast growth factor enhances myocardial collateral flow in a canine model. Am J Physiol., 1994; 266(4 Pt 2):H1588-H1595.

Bredee JJ. An improved ameroid constrictor. Preliminary communication. J Surg Res., 1969; 9(2):107-112.

Elzinga WE. Ameroid constrictor: uniform closure rates and a calibration procedure. J Appl Physiol., 1969; 27(3):419-421.

Chatterjee S, Rosensweig J. Hemodynamic validity of the ameroid-induced ischemic heart preparation. J Surg Res., 1968; 8(10):471-474.

Litvak J, Siderides LE, Vineberg A. Experimental production of coronary artery insufficiency and occlusion. Am Heart J., 1957; 53:505-518.

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Clinical Myocardial Ischemia Studies

Horvath KA, Ferguson TB Jr, Guyton RA, Edwards FH. Impact of unstable angina on outcomes of transmyocardial laser revascularization combined with coronary artery bypass grafting. Ann Thorac Surg., 2005 Dec;80(6):2082-5.

Galinanes M. New Prospects in Myocardial Surgical Revascularization. Rev Esp Cardiol. 2005 Dec;58 (12):1459-1468.

van der Sloot JA, Huikeshoven M, Tukkie R, Verberne HJ, van der Meulen J, van Eck-Smit BL, van Gemert MJ, Tijssen JG, Beek JF. Transmyocardial revascularization using an XeCl excimer laser: results of a randomized trial. Ann Thorac Surg., 2004 Sep;78(3):875-81

Lowe HC, Oesterle SN, He KL, Macneill BD, Burkhoff D. Outcomes following percutaneous coronary intervention in patients previously considered "without option": a subgroup analysis of the PACIFIC Trial. J Interv Cardiol., 2004 Apr;17(2):87-91.

Frazier OH, Tuzun E, Eichstadt H, Boyce SW, Lansing AM, March RJ, Sartori M, Kadipasaoglu KA. Transmyocardial laser revascularization as an adjunct to coronary artery bypass grafting: a randomized, multicenter study with 4-year follow-up. Tex Heart Inst J., 2004;31(3):231-9.

Kleiman NS, Patel NC, Allen KB, Simons M, Yla-Herttuala S, Griffin E, Dzau VJ. Evolving revascularization approaches for myocardial ischemia. Am J Cardiol., 2003 Nov 7;92 (9B):9N-17N. Review.

Emmett L, Iwanochko RM, Freeman MR, Barolet A, Lee DS, Husain M. Reversible regional wall motion abnormalities on exercise technetium-99m-gated cardiac single photon emission computed tomography predict high-grade angiographic stenoses. J Am Coll Cardiol., 2002; 39 (6):991-998.

Henry TD, Rocha-Singh K, Isner JM, Kereiakes DJ, Giordano FJ, Simons M, Losordo DW, Hendel RC, Bonow RO, Eppler SM, Zioncheck TF, Holmgren EB, McCluskey ER. Intracoronary administration of recombinant human vascular endothelial growth factor to patients with coronary artery disease. Am Heart J., 2001; 142(5):872-880.

Pagano D, Fath-Ordoubadi F, Beatt KJ, Townend JN, Bonser RS, Camici PG. Effects of coronary revascularisation on myocardial blood flow and coronary vasodilator reserve in hibernating myocardium. Heart, 2001; 85 (2):208-212.

Vanoverschelde JL, Melin JA. The pathophysiology of myocardial hibernation: current controversies and future directions. Prog Cardiovasc Dis., 2001; 43 (5):387-398.

Perrone-Filardi P, Chiariello M. The identification of myocardial hibernation in patients with ischemic heart failure by echocardiography and radionuclide studies. Prog Cardiovasc Dis., 2001; 43 (5):419-432.

Pierard LA, Melon PG, Lancellotti P, De Landsheere CM, Degueldre C, Kulbertus HE. Identification of viable myocardium early after acute myocardial infarction using closed-loop arbutamine echocardiography: comparison with positron emission tomography. Acta Cardiol., 2001; 56(6):387-394.

Rinaldi CA, Hall RJ. Myocardial stunning and hibernation in clinical practice. >Int J Clin Pract., 2000; 54(10):659-664.

Frazier OH, March RJ, Horvath KA. Transmyocardial revascularization with a carbon dioxide laser in patients with end-stage coronary artery disease. N Engl J Med., 1999; 341(14):1021-1028.

Elhendy A, Bax JJ, van Domburg RT, Valkema R, Cornel JH, Reijs AE, Krenning EP, Roelandt JR. Dobutamine stress thallium-201 single-photon emission tomography versus echocardiography for evaluation of the extent and location of coronary artery disease late after myocardial infarction. Eur J Nucl Med., 1999; 26 (5):467-473.

Pagano D, Bonser RS, Townend JN, Ordoubadi F, Lorenzoni R, Camici PG. Predictive value of dobutamine echocardiography and positron emission tomography in identifying hibernating myocardium in patients with postischaemic heart failure. Heart, 1998; 79(3):281-288.

Cornel JH, Bax JJ, Elhendy A, Reijs AE, Fioretti PM. Dobutamine stress-redistribution-reinjection versus rest-redistribution thallium-201 SPECT in the assessment of myocardial viability. Int J Card Imaging, 1997; 13(1):59-64.

Adams JN, Norton M, Trent RJ, Mikecz P, Walton S, Evans N. Incidence of hibernating myocardium after acute myocardial infarction treated with thrombolysis. Heart, 1996; 75 (5):442-446.

Schaper W. Angiogenesis in the adult heart. Basic Research in Cardiology, 1991; 2 (86 Suppl):51-56.

Levin DC, Beckmann CF, Sos TA, Sniderman K. Incomplete myocardial reperfusion despite a patent coronary bypass: a generally unrecognized shortcoming of the surgical approach to coronary artery disease. Radiology, 1982; 142(2):317-321.

Schaper W. The collateral circulation of the heart. New York: Elsevier, 1971.

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Congestive Heart Failure studies

Heerdt PM, Klotz S, Burkhoff D. Cardiomyopathic etiology and SERCA2a reverse remodeling during mechanical support of the failing human heart. Anesth Analg., 2006 Jan;102(1):32-7.

Patel AN, Geffner L, Vina RF, Saslavsky J, Urschel HC Jr, Kormos R, Benetti F. Surgical treatment for congestive heart failure with autologous adult stem cell transplantation: a prospective randomized study. J Thorac Cardiovasc Surg., 2005 Dec;130(6):1631-8. Epub 2005 Oct 26.

Zwisler AD, Schou L, Soja AM, Bronnum-Hansen H, Gluud C, Iversen L, Sigurd B, Madsen M, Fischer-Hansen J; DANREHAB group. A randomized clinical trial of hospital-based, comprehensive cardiac rehabilitation versus usual care for patients with congestive heart failure, ischemic heart disease, or high risk of ischemic heart disease (the DANREHAB trial)--design, intervention, and population. Am Heart J., 2005 Nov;150(5):899.

Nazarian S, Maisel WH, Miles JS, Tsang S, Stevenson LW, Stevenson WG. Impact of implantable cardioverter defibrillators on survival and recurrent hospitalization in advanced heart failure. Am Heart J., 2005 Nov;150(5):955-60.

Clegg AJ, Scott DA, Loveman E, Colquitt J, Hutchinson J, Royle P, Bryant J. The clinical and cost-effectiveness of left ventricular assist devices for end-stage heart failure: a systematic review and economic evaluation. Health Technol Assess., 2005 Nov;9(45):1-148.

Klotz S, Foronjy RF, Dickstein ML, Gu A, Garrelds IM, Danser AH, Oz MC, D'Armiento J, Burkhoff D. Mechanical unloading during left ventricular assist device support increases left ventricular collagen cross-linking and myocardial stiffness. Circulation, 2005 Jul 19;112(3):364-74. Epub 2005 Jul 8.

Haddad M, Lam K, Hendry P, Mesana T, Davies R. Left Ventricular Assist Devices for the Treatment of Congestive Heart Failure. Curr Treat Options Cardiovasc Med., 2005 May;7(1):47-54.

Stevenson LW, Miller LW, Desvigne-Nickens P, Ascheim DD, Parides MK, Renlund DG, Oren RM, Krueger SK, Costanzo MR, Wann LS, Levitan RG, Mancini D; REMATCH Investigators. Left ventricular assist device as destination for patients undergoing intravenous inotropic therapy: a subset analysis from REMATCH (Randomized Evaluation of Mechanical Assistance in Treatment of Chronic Heart Failure). Circulation, 2004 Aug 24;110 (8):975-81. Epub 2004 Aug 16.

Chaudhary KW, Rossman EI, Piacentino V 3rd, Kenessey A, Weber C, Gaughan JP, Ojamaa K, Klein I, Bers DM, Houser SR, Margulies KB. Altered myocardial Ca2+ cycling after left ventricular assist device support in the failing human heart. J Am Coll Cardiol., 2004 Aug 18;44(4):837-45.

Terracciano CM, Harding SE, Adamson D, Koban M, Tansley P, Birks EJ, Barton PJ, Yacoub MH. Changes in sarcolemmal Ca entry and sarcoplasmic reticulum Ca content in ventricular myocytes from patients with end-stage heart failure following myocardial recovery after combined pharmacological and ventricular assist device therapy. Eur Heart J., 2003 Jul;24(14):1329-39.

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Regenerative Medicine

Ye L, Haider HKh, Sim EK. Adult stem cells for cardiac repair: a choice between skeletal myoblasts and bone marrow stem cells. Exp Biol Med., (Maywood). 2006 Jan;231(1):8-19.

Grenier G, Rudnicki MA. The potential use of myogenic stem cells in regenerative medicine. Handbk Exp Pharmacol., 2006;(174):299-317.

Memon IA, Sawa Y, Miyagawa S, Taketani S, Matsuda H. Combined autologous cellular cardiomyoplasty with skeletal myoblasts and bone marrow cells in canine hearts for ischemic cardiomyopathy. J Thorac Cardiovasc Surg., 2005 Sep;130(3):646-53.

Dib N, Michler RE, Pagani FD, Wright S, Kereiakes DJ, Lengerich R, Binkley P, Buchele D, Anand I, Swingen C, Di Carli MF, Thomas JD, Jaber WA, Opie SR, Campbell A, McCarthy P, Yeager M, Dilsizian V, Griffith BP, Korn R, Kreuger SK, Ghazoul M, MacLellan WR, Fonarow G, Eisen HJ, Dinsmore J, Diethrich E. Safety and feasibility of autologous myoblast transplantation in patients with ischemic cardiomyopathy: four-year follow-up. Circulation, 2005 Sep 20;112(12):1748-55.

Dib N, McCarthy P, Campbell A, Yeager M, Pagani FD, Wright S, MacLellan WR, Fonarow G, Eisen HJ, Michler RE, Binkley P, Buchele D, Korn R, Ghazoul M, Dinsmore J, Opie SR, Diethrich E. Feasibility and safety of autologous myoblast transplantation in patients with ischemic cardiomyopathy. Cell Transplant., 2005;14(1):11-9.

Gowdak LH, Schettert IT, Rochitte CE, Lisboa LA, Dallan LA, Cesar LA, Krieger JE, Ramires JA, Oliveira SA. Cell therapy plus transmyocardial laser revascularization for refractory angina. Ann Thorac Surg., 2005 Aug;80(2):712-4.

He KL, Yi GH, Sherman W, Zhou H, Zhang GP, Gu A, Kao R, Haimes HB, Harvey J, Roos E, White D, Taylor DA, Wang J, Burkhoff D. Autologous skeletal myoblast transplantation improved hemodynamics and left ventricular function in chronic heart failure dogs. J Heart Lung Transplant., 2005 Nov;24 (11):1940-9. Epub 2005 Aug 24.

Moise KJ Jr. Umbilical cord stem cells. Obstet Gynecol., 2005 Dec;106(6):1393-407.

Kemp KC, Hows J, Donaldson C. Bone marrow-derived mesenchymal stem cells. Leuk Lymphoma, 2005 Nov;46 (11):1531-44.

Lerou PH, Daley GQ. Therapeutic potential of embryonic stem cells. Blood Rev., 2005 Nov;19 (6):321-31.

Badylak SF. Regenerative medicine and developmental biology: The role of the extracellular matrix. Anat Rec B New Anat., 2005 Nov;287(1):36-41.

Strem BM, Hicok KC, Zhu M, Wulur I, Alfonso Z, Schreiber RE, Fraser JK, Hedrick MH. Multipotential differentiation of adipose tissue-derived stem cells. Keio J Med., 2005 Sep;54(3):132-41. Review.

Rahaman MN, Mao JJ. Stem cell-based composite tissue constructs for regenerative medicine. Biotechnol Bioeng., 2005 Aug 5;91(3):261-84. Review.

Kume S. Stem-cell-based approaches for regenerative medicine. Dev Growth Differ., 2005 Aug;47 (6):393-402. Review.

Dinsmore JH, Dib N. An overview of myoblast transplantation for myocardial regeneration. Am Heart Hosp J., 2005 Summer;3(3):146-52. Review.

Klein HM, Ghodsizad A, Borowski A, Saleh A, Draganov J, Poll L, Stoldt V, Feifel N, Piecharczek C, Burchardt ER, Stockschlader M, Gams E. Autologous bone marrow-derived stem cell therapy in combination with TMLR. A novel therapeutic option for endstage coronary heart disease: report on 2 cases. Heart Surg Forum, 2004;7 (5):E416-9.

Angoulvant D, Fazel S, Li RK. Neovascularization derived from cell transplantation in ischemic myocardium. Mol Cell Biochem., 2004 Sep;264(1-2):133-42. Review.

Kofidis, J, deBruin JL, Hoyt G, Lebl D, Tanaka M, Yamane T, Chang CP, and Robbins RC: Injectable bioartificial myocardial tissue for large-scale intramural cell transfer and functional recovery of injured heart muscle. J Thoracic and CV Surgery, 2004;128(4):571-78.

Balsam LB, Wagers AJ, Christensen JL, Kofidis T, Weissman IL, Robbins RC Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature, 2004; 428: 6983: 668-73.

Shepherd BR, Chen HY, Smith CM, Gruionu G, Williams SK, Hoying JB. Rapid perfusion and network remodeling in a microvascular construct after implantation. Arterioscler Thromb Vasc Biol., 2004 May;24 (5):898-904. Epub 2004 Feb 26.

Kidd KR, Williams SK. Laminin-5-enriched extracellular matrix accelerates angiogenesis and neovascularization in association with ePTFE. J Biomed Mater Res A., 2004 May 1;69 (2):294-304.

Kidd KR, Nagle RB, Williams SK. Angiogenesis and neovascularization associated with extracellular matrix-modified porous implants. J Biomed Mater Res., 2002 Feb; 59 (2):366-77.

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Biomaterials

Alperin C, Zandstra PW, Woodhouse KA. Polyurethane films seeded with embryonic stem cell-derived cardiomyocytes for use in cardiac tissue engineering applications. Biomaterials, 2005 Dec;26(35):7377-86.

Davis ME, Hsieh PC, Grodzinsky AJ, Lee RT. Custom design of the cardiac microenvironment with biomaterials. Circ Res., 2005 Jul 8;97(1):8-15. Review.

Sigler M, Paul T, Grabitz RG. Biocompatibility screening in cardiovascular implants. Z Kardiol., 2005 Jun;94 (6):383-91. Review.

Leor J, Amsalem Y, Cohen S. Cells, scaffolds, and molecules for myocardial tissue engineering. Pharmacol Ther., 2005 Feb;105 (2):151-63. Epub 2004 Dec 8. Review.

Zammaretti P, Jaconi M. Cardiac tissue engineering: regeneration of the wounded heart. Curr Opin Biotechnol., 2004 Oct;15(5):430-4. Review.

Zisch AH, Lutolf MP, Hubbell JA. Biopolymeric delivery matrices for angiogenic growth factors. Cardiovasc Pathol., 2003 Nov-Dec;12 (6):295-310. Review.

Kidd K, Dal Ponte, D, Kellar RS, Williams SK. A Comparative Evaluation of Porous Material Implant Healing in the Rat and Mouse. Journal of Biomedical Materials Research, 59 (4): 682-689. 2002.

Kellar RS, Kleinert LB, Williams SK. Characterization of Angiogenesis and Inflammation Surrounding ePTFE Implanted on the Epicardium. Journal of Biomedical Materials Research, 61 (2): 226-233. 2002.

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Presentations

list pending

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Scientific Advisory Board

Gail K. Naughton, Ph.D., Head; Dr. Naughton contributes invaluable knowledge and focus to Theregen's vascular and cardiovascular product development efforts. She is a world-recognized pioneer in cell-based regenerative medicine and holds more than 80 patents, including several in Theregen's IP portfolio. She has received a National Inventor of the Year award for her pioneering work in tissue engineering. She is currently Dean, School of Business Administration, San Diego State University, and serves on numerous advisory boards and boards of directors for both commercial and non-profit organizations.

Robert C. Robbins, M.D., Member, chairs the Department of Cardiothoracic Surgery of Stanford University.s School of Medicine, where he also serves as Director of the Stanford Cardiovascular Institute and Co-Director of the Cardiac Clinical Center at Stanford University Hospital. Dr. Robbins has extensive research experience in the area of congestive heart failure. He is a Fellow of the American Heart Association, American College of Cardiology and the American College of Surgery.

Judith L. Swain, M.D., Member, a distinguished molecular cardiologist and former Chair of the Department of Medicine at the Stanford University School of Medicine, is now the first Director of the College of Integrated Life Sciences at the University of California, San Diego. She is Co-Director of the National Aeronautics and Space Administration (NASA) National Center for Space Biological Technologies, which focuses on biological measurements in outer space. She is a Director of the American Board of Internal Medicine and the Burroughs Wellcome Fund.

Stuart K. Williams, Ph.D., Member, brings extensive experience in cell-based regenerative medicine and cardiovascular therapeutics in his capacity as consultant and member of Theregen's Scientific Advisory Board. At the University of Arizona, Tucson, Dr. Williams is Professor and Chairman of the Biomedical Engineering Graduate Studies Program, and Director, Division of Biomedical Engineering, Arizona Research Laboratories. He has extensive expertise in cardiovascular applications of biomedical devices and cell-based therapeutics. Dr. Williams serves as a Board member or scientific advisor to several companies.

Robert S. Kellar, Ph.D., Member, brings significant commercial experience to Theregen.s SAB. He has managed R&D project teams responsible for clinical, regulatory, manufacturing, and packaging of commercialized medical devices. Previously, Dr. Kellar was at Advanced Tissue Sciences, Inc (ATS) in La Jolla, California. While at ATS, Dr. Kellar established a working local vivarium, managed research personnel, and managed a large GLP safety animal trial. Additionally, he has served as a lead scientist in discussions with the FDA on new biologic product regulations.

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Clinical Advisory Board

Frank Giordano, M.D., Yale University, Imaging Cardiology

Steven Goldman, M.D., University of Arizona, Echocardiology

Bartley Griffith, M.D., University of Maryland, Medicine, Lead Cardiothoracic Surgeon

Albert Sinusas, M.D., Yale University

George Tellides, M.D., Yale University

Hoang Thai, M.D., University of Arizona

 

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