Successful Autotransplantation of Microvessel Fragments into the Rat Heart

We examined whether microvessel fragments (Mvf), autologously transplanted with myofibroblasts (Mf) into the heart, could survive and form connections to the host’s coronary microcirculation. Neither achievement has been reported before in the heart. Mvf and Mf were prepared from Sprague-Dawley rat epididymal fat pads. A mixture of Mvf (labeled with the fluorescent probe DiI-acetylated low-density lipoprotein, DiI-Ac-LDL) and Mf was injected into the superficial myocardium under general anesthesia. Rats (n = 5 in each group) were killed on postoperative days 7, 14, 21, 42 and 49, and India ink was perfused through the coronary arteries. Frozen sections of the injected area were examined under fluorescence and light microscopes. Some DiI-Ac-LDL-labeled Mvf survived in each group, and India ink was present in the lumina of microvessels coincident with DiI-Ac-LDL-labeled autotransplanted Mvf. Hematoxylin and eosin staining revealed mild inflammatory reactions followed by some fibrosis at the injection sites. These findings indicate that autotransplanted Mvf can survive for at least 49 days, and that patent microvascular anastomoses can form between them and the host’s coronary microvessels. Possibly, autotransplantation of Mvf could lead to the development of a new collateral microcirculation, a phenomenon especially important in the ischemic heart.

[1]  S. Epstein,et al.  Effects of chronic systemic administration of basic fibroblast growth factor on collateral development in the canine heart. , 1995, Circulation.

[2]  D. Dichek,et al.  Gene therapy for restenosis: are we ready? , 1998, Circulation research.

[3]  J. Pearlman,et al.  Vascular endothelial growth factor administration in chronic myocardial ischemia. , 1996, The American journal of physiology.

[4]  N. Sato,et al.  Identification of non heparin-binding endothelial cell growth factor from rat myofibroblasts. , 1992, EXS.

[5]  T. Rosengart,et al.  Therapeutic angiogenesis: a comparative study of the angiogenic potential of acidic fibroblast growth factor and heparin. , 1997, Journal of vascular surgery.

[6]  Douglas Hanahan,et al.  Signaling Vascular Morphogenesis and Maintenance , 1997, Science.

[7]  S. Signoretti,et al.  Safety and efficacy of in vivo gene transfer into the porcine heart with replication-deficient, recombinant adenovirus vectors. , 1996, Gene therapy.

[8]  J. Isner,et al.  Gene transfer of naked DNA encoding for three isoforms of vascular endothelial growth factor stimulates collateral development in vivo. , 1996, Laboratory investigation; a journal of technical methods and pathology.

[9]  B. Lewis,et al.  Angiogenesis by gene therapy: a new horizon for myocardial revascularization? , 1997, Cardiovascular research.

[10]  E. Keshet,et al.  Upregulation of vascular endothelial growth factor expression induced by myocardial ischaemia: implications for coronary angiogenesis. , 1994, Cardiovascular research.

[11]  Y. Tsuchida,et al.  Effect of Autotransplantation of Microvessel Fragments on Experimental Random-Pattern Flaps in the Rat , 1998, European Surgical Research.

[12]  K. March,et al.  Gene therapy for restenosis: getting nearer the heart of the matter. , 1998, Circulation research.

[13]  R. Crystal,et al.  Direct in vivo gene transfer to canine myocardium using a replication-deficient adenovirus vector. , 1996, The Annals of thoracic surgery.

[14]  Y. Kira,et al.  Rapid induction of vascular endothelial growth factor expression by transient ischemia in rat heart. , 1994, The American journal of physiology.

[15]  J. Isner,et al.  Direct intramuscular gene transfer of naked DNA encoding vascular endothelial growth factor augments collateral development and tissue perfusion. , 1996, Circulation.

[16]  M. Neeman,et al.  Stabilization of vascular endothelial growth factor mRNA by hypoxia and hypoglycemia and coregulation with other ischemia-induced genes , 1995, Molecular and cellular biology.

[17]  Jason A. Lowry,et al.  Arterial gene therapy for therapeutic angiogenesis in patients with peripheral artery disease. , 1995, Circulation.

[18]  B. A. French,et al.  Direct in vivo gene transfer into porcine myocardium using replication-deficient adenoviral vectors. , 1994, Circulation.

[19]  B. V. von Specht,et al.  Induction of neoangiogenesis in ischemic myocardium by human growth factors: first clinical results of a new treatment of coronary heart disease. , 1998, Circulation.

[20]  E. Brogi,et al.  Therapeutic angiogenesis. A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model. , 1994, The Journal of clinical investigation.

[21]  Y. Uchida,et al.  Salvage of infarcted myocardium by angiogenic action of basic fibroblast growth factor. , 1992, Science.

[22]  B. Zetter,et al.  Identification and isolation of endothelial cells based on their increased uptake of acetylated-low density lipoprotein , 1984, The Journal of cell biology.

[23]  M. Capogrossi,et al.  Gene therapy for collateral vessel development. , 1997, Cardiovascular research.

[24]  J. Waltenberger Modulation of growth factor action: implications for the treatment of cardiovascular diseases. , 1997, Circulation.

[25]  J. Isner,et al.  Arterial gene transfer of acidic fibroblast growth factor for therapeutic angiogenesis in vivo: critical role of secretion signal in use of naked DNA. , 1997, Cardiovascular research.

[26]  N. Sato,et al.  Platelet-derived growth factor indirectly stimulates angiogenesis in vitro. , 1993, The American journal of pathology.

[27]  Y. Tsuchida,et al.  Direct evidence of a connection between autotransplanted microvessel fragments and the host microvascular system. , 1997, International journal of microcirculation, clinical and experimental.

[28]  N. Sato,et al.  Development of capillary networks from rat microvascular fragments in vitro: the role of myofibroblastic cells. , 1987, Microvascular research.

[29]  O. Stein,et al.  Bovine aortic endothelial cells display macrophage-like properties towards acetylated 125I-labelled low density lipoprotein. , 1980, Biochimica et biophysica acta.

[30]  Ronald G. Crystal,et al.  Transfer of Genes to Humans: Early Lessons and Obstacles to Success , 1995, Science.

[31]  J. Isner The role of angiogenic cytokines in cardiovascular disease. , 1996, Clinical immunology and immunopathology.

[32]  B.,et al.  Low Density Lipoprotein , 2022 .