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Efficacy of human adipose tissue-derived stem cells in cardiac muscle repair in an experimental acute myocardial infarction model using nude rats (Crl:NIH-Fox1RNU)

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Abstract

This study was designed to compare the efficacy of intraventricular (IV), intramyocardial (IM) or combined IV and IM injections of human adipose tissue-derived stem cells (hADSCs) administered either immediately, 5, or 10 days after induction of acute myocardial infarction (AMI) in a nude rat model. Acute myocardial infarction was induced in 99, adult (250–350 g BW), male nude rats strain Crl:NIH-Fox1RNU. Rats received either no cells (group I, n = 15) or 2 million, hADSCs as follows: group II (n = 19) IV injection immediately after AMI; group III (n = 18) IV injection 5 days after AMI; group IV (n = 15) IV injection 5 days and IM injection 10 days after AMI; group V (n = 17) IV injection immediately after AMI and IM injection 10 days after AMI and group VI (n = 15) IM injection 10 days after AMI. Tissue sections from hearts were studied using H&E and immunohistochemistry. In the control group, there was a tendency toward granulation tissue formation, active phagocytosis, and variable angiogenesis when evaluated at 10 days, early fibrosis when evaluated at 30 days, and established fibrosis when evaluated at 60 days. However, hADSC-treated groups showed a tendency toward cardiomyocyte regeneration and prominent angiogenesis when evaluated at 10 days and smaller infarction size when evaluated at 30 and 60 days. The present study showed a significantly decreased amount of scar tissue following myocardial infarction and enhanced regenerative capacity of myocardial cells following a single, intraventricular injection of 2 million hADSCs immediately after AMI.

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Abbreviations

AMI:

Acute myocardial infarction

BMSCs:

Bone marrow-derived stem cells

hADSCs:

Human adipose tissue-derived stem cells

JUST-ACUC:

Institutional animal care and use committee of Jordan University of Science and Technology

LAD:

Left descending coronary artery

PBS:

Phosphate-buffered saline

LVEDD:

Left ventricular end diastolic dimension

LVESD:

Left ventricular end systolic dimension

FS %:

Fraction of shortening

References

  • Alzaben KR, Abu-Halaweh SA, Aloweidi AS, Bani Ismail ZA et al (2009) Using nasal speculum for rat endotracheal intubation. Am J Appl Sci 6:507–511

    Article  Google Scholar 

  • Anversa P, Li P, Zhang X, Olivetti G, Capasso JM (1993) Ischaemic myocardial injury and ventricular remodeling. Cardiovasc Res 27:145–157

    Article  CAS  PubMed  Google Scholar 

  • Assmus B, Schachinger V, Teupe C et al (2002) Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI). Circulation 106:3009–3017

    Article  PubMed  Google Scholar 

  • Bani Ismail ZA, Al-Majali A, Alzaben KR et al (2009) Haematology and plasma biochemical analysis in experimental acute myocardial infarction in a nude rat model. Comp Clin Pathol 18(4)

  • Cai L, Johnstone BH, Cook TG, Tan J, Fishbein MC, Chen P, March KL (2009) Human adipose tissue-derived stem cells induce angiogenesis and nerve sprouting following myocardial infarction, in conjunction with potent preservation of cardiac function. Stem Cells 27:230–237

    Article  CAS  PubMed  Google Scholar 

  • Chimenti S, Carlo E, Masson S, Bai A, Latini R (2004) Myocardial infarction: animal models. Methods Mol Biol 225(98):217–226

    Google Scholar 

  • Chiu RC, Zibaitis A, Kao RL (1995) Cellular cardiomyoplasty: myocardial regeneration with satellite cell implantation. Ann Thorac Surg 60:12–18

    CAS  PubMed  Google Scholar 

  • Deacon T, Schumacher J, Dinsmore J, Thomas C, Palmer P, Kott S, Edge A, Penney A, Kassissieh S, Dempsey P, Isacson O (1997) Histological evidence of fetal pig neural cell survival after transplantation into a patient with Parkinson's disease. Nat Med 3:350–353

    Article  CAS  PubMed  Google Scholar 

  • Fletcher PJ, Pfeffer JM, Pfeffer MA, Braunwald E (1981) Left ventricular diastolic pressure-volume relations in rats with healed myocardial infarction: effects on systolic function. Circ Res 49:618–626

    CAS  PubMed  Google Scholar 

  • Frangioni JV, Hajjar RJ (2004) In vivo tracking of stem cells for clinical trials in cardiovascular disease. Circulation 110:3378–3383

    Article  PubMed  Google Scholar 

  • Jackson KA, Majka SM, Wang H, Pocius J, Hartley CJ, Majesky MW, Entman ML, Michael LH, Hirschi KK, Goodell MA (2001) Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest 107:1395–1402

    Article  CAS  PubMed  Google Scholar 

  • Jain M, DerSimonian H, Brenner BDA, DA NS, Teller P, Edge ASB, Zawadzka A, Wetzel K, Sawyer DB, Colucci WS, Apstein CS, Liao R (2001) Cell therapy attenuates deleterious ventricular remodeling and improves cardiac performance after myocardial infarction. Circulation 103:1920–1927

    CAS  PubMed  Google Scholar 

  • Kocher AA, Schuster MD, Szabolcs MJ et al (2001) Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med 7:430–436

    Article  CAS  PubMed  Google Scholar 

  • Koh GY, Klug MG, Soonpaa MH, Field LJ (1993) Differentiation and long-term survival of C2C12 myoblast grafts in heart. J Clin Invest 92:1548–1554

    Article  CAS  PubMed  Google Scholar 

  • Kuethe F, Richartz BM, Sayer HG, Kasper C, Werner G, Höffken K, Figulla H (2004) Lack of regeneration of myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans with large anterior myocardial infarctions. Int J Cardiol 97:123–127

    Article  PubMed  Google Scholar 

  • Leor J, Prentice H, Sartorelli V, Quinones MJ, Patterson M, Kedes LK, Kloner RA (1997) Gene transfer and cell transplant: an experimental approach to repair a “broken heart”. Cardiovasc Res 35:431–441

    Article  CAS  PubMed  Google Scholar 

  • Miranville A, Heeschen C, Sengenes C et al (2004) Improvement of postnatal neovascularization by human adipose tissue-derived stem cells. Circulation 110:349–355

    Article  CAS  PubMed  Google Scholar 

  • Miyagawa S, Sawa Y, Taketani S et al (2002) Myocardial regeneration therapy for heart failure: hepatocyte growth factor enhances the effect of cellular cardiomyoplasty. Circulation 105:2556–2561

    Article  CAS  PubMed  Google Scholar 

  • Möllmann M, Nef HM, Kostin S, von Kalle C, Pilz I, Weber M, Schaper J, Hamm CW, Elsässer A (2006) Bone marrow-derived cells contribute to infarct remodeling. Cardiovasc Res 71:661–671

    Article  PubMed  Google Scholar 

  • Murry CE, Wiseman RW, Schwartz SM, Hauschka SD (1996) Skeletal myoblast transplantation for repair of myocardial necrosis. J Clin Invest 98:2512–2523

    Article  CAS  PubMed  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, Anversa P (2001a) Bone marrow cells regenerate infarcted myocardium. Nature 410:701–705

    Article  CAS  PubMed  Google Scholar 

  • Orlic D, Kajstura J, Chimenti S, Limana F, Jakoniuk I, Quaini F, Nadal-Ginard B, Bodine DM, Leri A, Anversa P (2001b) Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci USA 98:10344–10349

    Article  CAS  PubMed  Google Scholar 

  • Pfeffer MA, Braunwald E (1990) Ventricular remodeling after myocardial infarction: experimental observations and clinical implications. Circulation 81:1161–1172

    CAS  PubMed  Google Scholar 

  • Pfeffer MA, Pfeffer JM, Fishbein MC, Fletcher PJ, Spadaro J, Kloner RA, Braunwald E (1979) Myocardial infarct size and ventricular function in rats. Circ Res 44:503–512

    CAS  PubMed  Google Scholar 

  • Pfeffer JM, Pfeffer MA, Fletcher PJ, Braunwald E (1991) Progressive ventricular remodeling in rat with myocardial infarction. Am J Physiol 260:H1406–H1414

    CAS  PubMed  Google Scholar 

  • Planat-Benard V, Silvestre JS, Cousin B et al (2004) Plasticity of human adipose lineage cells toward endothelial cells: physiological and therapeutic perspectives. Circulation 109:656–663

    Article  PubMed  Google Scholar 

  • Reinlib L, Field L (2000) Cell transplantation as future therapy for cardiovascular disease? A workshop of the National Heart, Lung, and Blood Institute. Circulation 101:E182–E187

    CAS  PubMed  Google Scholar 

  • Roell W, Lu ZJ, Bloch W, Siedner S, Tiemann K, Xia Y, Stoecker E, Fleischmann M, Bohlen H, Stehle R, Kolossov E, Brem G, Addicks K, Pfitzer G, Welz A, Hescheler J, Fleischmann BK (2002) Cellular cardiomyoplasty improves survival after myocardial injury. Circulation 105:2435–2441

    Article  PubMed  Google Scholar 

  • Strauer BE, Brehm M, Zeus T, Köstering M, Hernandez A, Sorg RV, Kögler G, Wernet P (2002) Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 106:1913–1918

    Article  PubMed  Google Scholar 

  • Tomita S, Li RK, Weisel RD et al (1999) Autologous transplantation of bone marrow cells improves damaged heart function. Circulation 100(Suppl. 19):II247–II256

    CAS  PubMed  Google Scholar 

  • Valina C, Pinkernell K, Song Y, Bai X, Sadat S, Campeau RJ, Le Jemtel TH, Alt E (2007) Intracoronary administration of autologous adipose tissue-derived stem cells improves left ventricular function, perfusion, and remodelling after acute myocardial infarction. Eur Heart J 28:2667–2677

    Article  PubMed  Google Scholar 

  • Wang J, Bo H, Meng X et al (2006) A simple and fast experimental model of myocardial infarction in the mouse. Lab Anim 33:290–293

    Google Scholar 

  • Wayman NS, McDonald MC, Chatterjee PK et al (2003) Models of coronary artery occlusion and reperfusion for the discovery of novel antiischemic and antiinflammatory drugs for the heart. Methods Mol Biol 225:199–208

    CAS  PubMed  Google Scholar 

  • Wollert KC, Meyer GP, Lotz J et al (2004) Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 364:141–148

    Article  PubMed  Google Scholar 

  • Zuk PA, Zhu M, Mizuno H et al (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7:211–228

    Article  CAS  PubMed  Google Scholar 

  • Zuk PA, Zhu M, Ashjian P et al (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 3:4279–4295

    Article  Google Scholar 

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Acknowledgments

This project was sponsored by Bioheart, Inc, USA. The authors would like to thank the sponsors, University of Jordan, Jordan University of Science and Technology, Dr. Omar Alshobaki, The Animal House staff and animal care takers, Professor Abdallah Abbadi, Director of Hematology and stem cell laboratory University of Jordan, Faculty of Medicine, Mr. Mohammad Al-Zu'bi and Miss Shereen Kklouf for their help and hard work.

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Authors and Affiliations

  1. Division of Cardiothoracic Surgery, Department of Surgery, Faculty of Medicine, University of Jordan, P.O. Box 13857, Amman, 11942, Jordan

    Mahmoud Abu-Abeeleh, Ismail Matalka, Zuhair A. Bani Ismail, Khaled R. Alzaben, Sami A. Abu-Halaweh, Abdelkarim S. Aloweidi, Iyad A. Al-Ammouri, Mohamed K. Al-Essa, Sameer K. Jabaiti, Moaath M. Alsmady, Omar Alshobaki, Mohmmad Alqudah, Samir Albashir, Raed Ennab, Mohammad Jamous, Ahmad Al-Majali & Jaafar Abu-Abeeleh

  2. Department of Pathology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, 22110, Jordan

    Ismail Matalka, Mohmmad Alqudah & Samir Albashir

  3. Department of Veterinary Clinical Sciences, Faculty of Veterinary Medicine, Jordan University of Science and Technology, Irbid, 22110, Jordan

    Zuhair A. Bani Ismail & Ahmad Al-Majali

  4. Department of Physioology, Faculty of Medicine, University of Jordan, Amman, 11942, Jordan

    Mohamed K. Al-Essa

  5. Department of Anesthesia, Faculty of Medicine, University of Jordan, Amman, 11942, Jordan

    Khaled R. Alzaben, Sami A. Abu-Halaweh & Abdelkarim S. Aloweidi

  6. Department of Pediatrics, Faculty of Medicine, University of Jordan, Amman, 11942, Jordan

    Iyad A. Al-Ammouri

  7. Division PLASTIC Surgery, Department of Surgery, Faculty of Medicine, University of Jordan, Amman, 11942, Jordan

    Sameer K. Jabaiti

  8. Ibn Khaldoon Plastic Surgery Center, Amman, 11942, Jordan

    Omar Alshobaki

  9. Department of Neurosciences Faculty of Medicine, Jordan University of Science and Technology, Irbid, 22110, Jordan

    Mohammad Jamous

  10. Department of Pharmacy, Royal Medical Survices, P.O. Box 13857, Amman, 11942, Jordan

    Jaafar Abu-Abeeleh

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  1. Mahmoud Abu-Abeeleh
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  2. Ismail Matalka
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  3. Zuhair A. Bani Ismail
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Correspondence to Mahmoud Abu-Abeeleh.

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Abu-Abeeleh, M., Matalka, I., Bani Ismail, Z.A. et al. Efficacy of human adipose tissue-derived stem cells in cardiac muscle repair in an experimental acute myocardial infarction model using nude rats (Crl:NIH-Fox1RNU). Comp Clin Pathol 19, 593–600 (2010). https://doi.org/10.1007/s00580-009-0927-3

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