Skip to main content
Log in

Green Fluorescent Protein-Transgenic Rat as a Tool for Study of Transplantation and Regeneration in Myocardium

  • Published:
Cardiovascular Engineering: An International Journal

Abstract

Cell transplantation and regeneration therapy are potentially new therapeutic approaches for cardiovascular disease. Transgenic (tg) animals for reporter genes would be useful to follow the cell lineage and differentiation during development and regeneration processes. In the present study, we developed green fluorescent protein (GFP)-tg rats and evaluated them as a tool for the study of cardiomyocyte transplantation and regeneration. The myocardium and bone marrow cells derived from GFP-tg rats strongly expressed GFP. Because neonatal rat cultured cardiomyocytes also strongly expressed GFP, we transplanted GFP-tg rat-derived cardiomyocytes in a rat myocardial infarction (MI) model. Survival of GFP-tg rat-derived cardiomyocytes was confirmed. We further investigated whether bone marrow cells could differentiate into cardiomyocytes using this GFP-tg rat-derived bone marrow cells in vitro and in vivo. GFP-tg rat-derived bone marrow cells differentiated into cardiomyocyte- like cells (cardiac troponin I-expressed cells) by co-culture with wild rat cultured cardiomyocytes in vitro. Furthermore, differentiation of bone marrow cells into cardiomyocyte-like cells was observed by injection of GFP-tg rat-derived bone marrow cells in a rat MI model in vivo. These findings suggest that GFP-tg rats are a useful and valuable tool for the study of transplantation and regeneration in myocardium.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Ajiki T, Takahashi M, Inoue S, Sakuma Y, Oyama S, Kaneko T, Hakamata Y, Murakami T, Kume A, Kariya Y, Hoshino Y, and Kobayashi E. Generation of donor hematolymphoid cells after rat-limb composite grafting. Transplantation75: 631-636, 2003.

    Google Scholar 

  • Anversa, P, Fitzpatrick D, Argani S, and Capasso JM. Myocyte mitotic division in the aging mammalian rat heart. Circ Res69: 1159-1164, 1991.

    Google Scholar 

  • Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M, Kearne M, Magner M, and Isner JM. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res85: 221-228, 1999.

    Google Scholar 

  • Chiu RC, Zibaitis A, and Kao RL. Cellular cardiomyoplasty: Myocardial regeneration with satellite cell implantation. Ann Thorac Surg60: 12-18, 1995.

    Google Scholar 

  • Ferrari G, Cusella-De Angelis G, Coletta M, Paolucci E, Stornaiuolo A, Cossu G, and Mavilio F. Muscle regeneration by bone marrow-derived myogenic progenitors. Science279: 1528-1530, 1998.

    Google Scholar 

  • Hakamata Y, Tahara K, Uchida H, Sakuma Y, Nakamura M, Kume A, Murakami T, Takahashi M, Takahashi, R, Hirabayashi M, Ueda M, Miyoshi I, Kasai N, and Kobayashi E. Green fluorescent protein-transgenic rat: A tool for organ transplantation research. Biochem Biophys Res Commun286: 779-785, 2001.

    Google Scholar 

  • Hughes S. Cadiac stem cells. J Pathol197: 468-478, 2002.

    Google Scholar 

  • Ianus A, Holz GG, Theise ND, and Hussain MA. In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. J Clin Invest111: 843-850, 2003.

    Google Scholar 

  • Jackson KA, Majka SM, Wang H, Pocius J, Hartley CJ, Majesky MW, Entman ML, Michael LH, Hirschi KK, and Goodell MA. Regeneration of ischemic cardiac muscle and vascular endothelium by adults stem cells. J Clin Invest107: 1395-1402, 2001.

    Google Scholar 

  • Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, and Verfaillie CM. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature418: 41-49, 2002.

    Google Scholar 

  • Kawamoto A, Gwon HC, Iwaguro H, Yamaguchi JI, Uchida S, Masuda H, Silver M, Ma H, Kearney M, Isner JM, and Asahara T. Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia. Circulation103: 634-637, 2001.

    Google Scholar 

  • Kocher AA, Schuster MD, Szabolcs MJ, Takuma S, Burkhoff D, Wang J, Homma S, Edwards NM, and Itescu S. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med7: 430-436, 2001.

    Google Scholar 

  • Kotton DN, Ma BY, Cardoso WV, Sanderson EA, Summer RS, Williams MC, and Fine A. Bone marrow-derived cells as progenitors of lung alveolar epithelium. Development128: 5181-5188, 2001.

    Google Scholar 

  • Li RK, Jia ZQ, Weisel RD, Mickle DA, Zhang J, Mohabeer MK, Rao V, and Ivanov J. Cardiomyocyte transplantation improves heart function. Ann Thorac Surg62: 654-660; discussion 660–651, 1996.

    Google Scholar 

  • Makino S, Fukuda K, Miyoshi S, Konishi F, Kodama H, Pan J, Sano M, Takahashi T, Hori S, Abe H, Hata J, Umezawa A, and Ogawa S. Cardiomyocytes can be generated from marrow stromal cells in vitro. J Clin Invest103: 697-705, 1999.

    Google Scholar 

  • Orlic D, Hill JM, and Arai AE. Stem cells for myocardial regeneration. Circ Res91: 1092-1102, 2002.

    Google Scholar 

  • Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, and Anversa P. Bone marrow cells regenerate infarcted myocardium. Nature410: 701-705, 2001.

    Google Scholar 

  • Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N, Boggs SS, Greenberger JS, and Goff JP. Bone marrow as a potential source of hepatic oval cells. Science284: 1168-1170, 1999.

    Google Scholar 

  • Rangappa S, Fen C, Lee EH, Bongso A, and Wei ES. Transformation of adult mesenchymal stem cells isolated from the fatty tissue into cardiomyocytes. Ann Thorac Surg75: 775-779, 2003.

    Google Scholar 

  • Reinecke H, Zhang M, Bartosek T, and Murry CE. Survival, integration, and differentiation, of cardiomyocyte grafts: A study in normal and injured rat hearts. Circulation100: 193-202, 1999.

    Google Scholar 

  • Sasaki M, Honmou O, Akiyama Y, Uede T, Hashi K, and Kocsis JD. Transplantation of an acutely isolated bone marrow fraction repairs demyelinated adult rat spinal cord axons. Glia35: 26-34, 2001.

    Google Scholar 

  • Sata M, Saiura A, Kunisato A, Tojo A, Okada S, Tokuhisa T, Hirai H, Makuuchi M, Hirata Y, and Nagai R. Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis. Nat Med8: 403-409, 2002.

    Google Scholar 

  • Scorsin M, Marotte, F, Sabri A, Le Dref O, Demirag M, Samuel JL, Rappaport L, and Mensache P. can grafted cardiomyocytes colonize peri-infarct myocardial areas? Circulation94: II337-II340, 1996.

    Google Scholar 

  • Shimizu K, Sugiyama S, Aikawa M, Fukumoto Y, Rabkin E, Libby P, and Mitchell RN. Host bone-marrow cells are a source of donor intimal smooth-muscle-like cells in murine aortic transplant arteriopathy. Nat Med7: 738-741, 2001.

    Google Scholar 

  • Takahashi M, Nishihira J, Shimpo M, Mizue Y, Ueno S, Mano H, Kobayashi E, Ikeda U, and Shimada K. Macrophage migration inhibitory factor as a redox-sensitive cytokine in cardiac myocytes. Cardiovasc Res52: 438-445, 2001.

    Google Scholar 

  • Terada N, Hamazaki T, Oka M, Hoki M, Mastalerz DM, Nakano Y, Meyer EM, Morel L, Petersen BE, and Scott EW. Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature416: 542-545, 2002.

    Google Scholar 

  • Tomita S, Li, RK, Weisel RD, Mickle DA, Kim EJ, Sakai T, and Jia ZQ. Autologous transplantation of bone marrow cells improves damaged heart function. Circulation100: II247-II256, 1999.

    Google Scholar 

  • Tomita S, Nakatani T, Fukuhara S, Morisaki T, Yutani C, and Kitamura S. Bone marrow stromal cells contract synchronously with cardiomyocytes in a coculture system. Jpn J Thorac Cardiovasc Surg50: 321-324, 2002.

    Google Scholar 

  • Wang JS, Shum-Tim D, Chedrawy E, and Chiu RC. The coronary delivery of marrow stromal cells for myocardial regeneration: Pathophysiologic and therapeutic implications. J Thorac Cardiovasc Surg122: 699-705, 2001.

    Google Scholar 

  • Ying QL, Nichols J, Evans EP, and Smith AG. Changing potency by spontaneous fusion. Nature416: 545-548, 2002.

    Google Scholar 

  • Yoon PD, Kao RL, and Magovern GJ. Myocardial regeneration. Transplanting satellite cells into damaged myocardium. Tex Heart Inst J.22: 119-125, 1995.

    Google Scholar 

  • Zambrowicz BP, Imamoto A, Fiering S, Herzenberg LA, Kerr WG, and Soriano P. Disruption of overlapping transcripts in the ROSA beta geo 26 gene trap strain leads to widespread expression of beta-galactosidase in mouse embryos and hematopoietic cells. Proc Natl Acad Sci USA94: 3789-3794, 1997.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Takahashi, M., Hakamata, Y., Takeda, Si. et al. Green Fluorescent Protein-Transgenic Rat as a Tool for Study of Transplantation and Regeneration in Myocardium. Cardiovascular Engineering 3, 63–69 (2003). https://doi.org/10.1023/A:1025563515836

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1025563515836

Navigation