Migration of intravenously grafted mesenchymal stem cells to injured heart in rats

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Journal Title:
ACTA PHYSIOLOGICA SINICA
Issue:
Volume 57, Issue 05, 2005
DOI:
Key Word:
mesenchymal stem cell;tissue injury;migration;heart

Abstract: The present study aimed to determine the role of tissue injury in migration of mesenchymal stem cells (MSCs) intravenously transplanted into heart and to establish experimental basis for improving stem cell therapy in its targeting and effectiveness. MSCs were isolated from bone marrow of male Sprague-Dawley rats and purified by density centrifuge and adhered to the culture plate in vitro.Female rats were divided randomly into four groups. Myocardial ischemia (MI) transplanted group received MSCs infusion through tail vein 3 h after MI and compared with sham-operated group or normal group with MSCs infusion, or control group received culture medium infusion. MI was created in female rats by ligating the left anterior descending coronary artery. The heart was harvested 1 week and 8 weeks after transplantation. The characteristics of migration of MSCs to heart were detected with expression of sry gene of Y chromosome by using fluorescence in situ hybridization (FISH). Ultrastructural changes of the ischemic myocardium of the recipient rats were observed by transmission electron microscope (TEM). One week or 8 weeks after transplantation, sry positive cells were observed in the cardiac tissue in both of MI transplanted group and sham-operated group, the number of sry positive cells being significantly higher in MI transplanted group (P<0.01). No significant difference was found in the number of sry positive cells between 1 week and 8 weeks after transplantation. No sry positive cells were observed in the hearts of control and normal group. In addition, the ultrastructure of some cells located in the peri-infarct area of MI rats with MSCs transplantation was similar to that of MSCs cultured in vitro. These results indicate that MSCs are capable of migrating towards ischemic myocardium in vivo and the fastigium of migration might appear around 1 week after MI. The tissue injury and its degree play an important role in the migration of MSCs.

  • [1]Blau HM, Brazelton TR, Weimann JM. The evolving concept of a stem cell: entity or function? Cell 2001: 105(7): 829-841.
  • [2]Pittenger MF, Martin BJ. Mesenchymal stem cells and their potential as cardiac therapeutics. Circ Res 2004: 95(1): 9-20.
  • [3]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, Verfaillie CM. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002: 418(6983): 41-49.
  • [4]Krause DS, Theise ND, Collector MI, Henegariu O, Hwang S,Gardner R, Neutzel S, Sharkis SJ. Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 2001:105 (3): 369-377.
  • [5]Wagers AJ, Weissman IL. Plasticity of adult stem cell. Cell 2004:116(5): 639-648.
  • [6]Strauer B, Komowski R. Stem cell therapy in perspective.Circulation 2003: 107(7): 929-934.
  • [7]Xiao YF. Cardiac application of embryonic stem cell. Acta Physiol Sin (生理学报) 2003: 55(5): 493-504.
  • [8]Forrester JS, Price M J, Makkar RR. Stem cell repair of infarcted myocardium: an overview for clinicians. Circulation 2003: 108(9): 1139-1145.
  • [9]Tropel P, Noel D, Platet N, Legrand P, Benabid AL, Berger F.Isolation and characterisation of mesenchymal stem cells from adult mouse bone marrow. Exp Cell Res 2004: 295( 2): 395-406
  • [10]Bianco P, Riminucci M, Gronthos S, Robey PG. Bone marrow stromal stem cells: nature, biology, and potential applications.Stem cells 2001: 19(3): 180-192.
  • [11]Gozzetti A, Le Beau MM. Fluorescence in situ hybridization: use and limitations. Semin Hematol 2000: 37(4): 320-333.
  • [12]Anjos-Afonso F, Siapati EK, Bonnet D. In vivo contribution of murine mesenchymal stem cells into multiple cell-types under minimal damage conditions. J Cell Sci 2004: 117(Pt 23): 5655-5664.
  • [13]Yeh ET, Zhang S, Wu HD, Kobling M, Willerson JT, Estrov Z.Transdifferentiation of human peripheral blood CD34+-enriched cell population into cardiomyocytes, endothelial cells, and smooth muscle cells in vivo. Circulation 2003: 108(17): 2070-2073.
  • [14]Frangogiannis NG, Smith CW, Entman ML. The inflammatory response in myocardial infarction. Cardiovasc Res 2002: 53(1):31-47.
  • [15]Orlic D, Hill JM, Arai AE. Stem cells for myocardial regeneration.Cir Res 2002: 91(12): 1092-1102.
  • [16]Christopherson KW 2nd, Hangoc G, Mantel CR, Broxmeyer HE.Modulation of hematopoietic stem cell homing and engraftment by CD26. Science 2004: 305(5686): 1000-1003.
  • [17]Sauer H, Hescheler J, Wartenberg M. Cardiac differentiation of mesenchymal stem cells in sex mis-matched transplanted hearts:self-repair or just a visit? Cardiovasc Res 2002: 56(3): 357-358.
  • [18]Barbash IM, Chouraqui P, Baron J, Feinberg MS, Etzion S,Tessone A, Miller L, Guetta E, Zipori D, Kedes LH, Kloner RA,Leor J. Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium. Circulation 2003: 108(7):863-868.
  • [19]Chu K, Kim M, Park K, Jeong SW, Park HK, Jung KH, Lee ST,Kang L, Lee K, Park DK, Kim SU, Roh JK. Human neural stem cells improve sensorimotor deficits in the adult rat brain with experimental focal ischemia. Brain Res 2004: 1016(2): 145-153.
  • [20]Abbott JD, Huang Y, Liu D, Hickey R, Krause DS, Giordano FJ.Stromal cell-derived factor- 1 alpha plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury. Circulation 2004: 110(21): 3300-3305.
  • [21]Perin EC, Geng YJ, Willerson JT. Adult stem cell therapy in perspective. Circulation 2003: 107(7): 935-938.
  • [22]Jiang WH, Ma AQ. Stem cell circulation and its potential application. Chin Med J 2003: 83(21): 1923-1925.
  • [23]Wollert KC, Drexler H. Clinical applications of stem cells for the heart. Circ Res 2005: 96(2): 151-163.
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