Direct Myocardial Implantation of Human Fetal Stem Cells in Heart Failure Patients: Long-term Results

Authors

  • Federico Benetti
  • Ernesto Peñherrera
  • Teodoro Maldonado
  • Yan Duarte Vera
  • Valvanur Subramanian
  • Luis Geffner

DOI:

https://doi.org/10.1532/HSF98.20091130

Abstract

Background: End-stage heart failure (HF) is refractory to current standard medical therapy, and the number of donor hearts is insufficient to meet the demand for transplantation. Recent studies suggest autologous stem cell therapy may regenerate cardiomyocytes, stimulate neovascularization, and improve cardiac function and clinical status. Although human fetal-derived stem cells (HFDSCs) have been studied for the treatment of a variety of conditions, no clinical studies have been reported to date on their use in treating HF. We sought to determine the efficacy and safety of HFDSC treatment in HF patients.

Methods and Results: Direct myocardial transplantation of HFDSCs by open-chest surgical procedure was performed in 10 patients with HF due to nonischemic, nonchagasic dilated cardiomyopathy. Before and after the procedure, and with no changes in their preoperative doses of medications (digoxin, furosemide, spironolactone, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, betablockers), patients were assessed for New York Heart Association (NYHA) class, performance in the exercise tolerance test (ETT), ejection fraction (EF), left ventricular end-diastolic dimension (LVEDD) via transthoracic echocardiography, performance in the 6-minute walk test, and performance in the Minnesota congestive HF test. All 10 patients survived the operation. One patient had a stroke 3 days after the procedure, and although she later recovered, she was unable to perform the follow-up tests. Another male patient experienced pericardial effusion 3 weeks after the procedure. Although it resolved spontaneously, the patient abandoned his control tests and died 5 months after the procedure. An autopsy of the myocardium suggested that new young cells were present in the cardiomyocyte mix. At 40 months, the mean (±SD) NYHA class decreased from 3.4 ± 0.5 to 1.33 ± 0.5 (P = .001); the mean EF increased 31%, from 26.6% ± 4% to 34.8% ± 7.2% (P = .005); and the mean ETT increased 291.3%, from 4.25 minutes to 16.63 minutes (128.9% increase in metabolic equivalents, from 2.46 to 5.63) (P < .0001); the mean LVEDD decreased 15%, from 6.85 ± 0.6 cm to 5.80 ± 0.58 cm (P < .001); mean performance in the 6-minute walk test increased by 43.2%, from 251 ± 113.1 seconds to 360 ± 0 seconds (P = .01); the mean distance increased 64.4%, from 284.4 ± 144.9 m to 468.2 ± 89.8 m (P = .004); and the mean result in the Minnesota test decreased from 71 ± 27.3 to 6 ± 5.9 (P < .001).

Conclusion: Although these initial findings suggest direct myocardial implantation of HFDSCs is feasible and improves cardiac function in HF patients at 40 months, more clinical research is required to confirm these observations.

References

[ASA/AHA] American Stroke Association, American Heart Association. 2005. Heart disease and stroke statistics—2005 update. Available at: http://www.americanheart.org/downloadable/heart/1105390918119HDSStats2005Update.pdf'>http://www.americanheart.org/downloadable/heart/1105390918119HDSStats2005Update.pdfnFujii T, Yau TM, Weisel RD, et al. 2003. Cell transplantation to prevent heart failure: a comparison of cell types. Ann Thorac Surg 76:2062-70.nGrischenko VI, Bobirova LE, Dvornek IL, Bobirova VM. 2003. Use of biotechnology in treatment of type 1 diabetes. Transplantology 4:16-9.nHunt SA, Baker DW, Chin MH, et al. 2001. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). Circulation 104:2996-3007.nJones RC, Francis GS, Lauer MS. 2004. Predictors of mortality in patients with heart failure and preserved systolic function in the digitalis investigation group trial. J Am Coll Cardiol 44:1025-9.nKang HJ, Kim HS, Zhang SY, et al. 2004. Effects of intracoronary infusion of peripheral blood stem-cells mobilised with granulocyte-colony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction: the MAGIC cell randomised clinical trial. Lancet 363:751-6.nKocher 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 7:430-6.nO'Donoghue K, Fisk NM. 2004. Fetal stem cells. Best Pract Res Clin Obstet Gynaecol 18:853-75.nOrlic D, Kajstura J, Chimenti S, Jakoniuk I, et al. 2001. Bone marrow cells regenerate infarcted myocardium. Nature 410:701-5.nOrlic D, Kajstura J, Chimenti S, et al. 2001. Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci U S A 98:10344-9.nPatel A, Geffner L, Viña RF, et al. 2005. Surgical treatment for congestive heart failure with autologous adult stem cell transplantation. A prospective randomized study. J Thorac Cardiovasc Surg 130:1631-8.nPerin EC, Dohmann HF, Borojevic R, et al. 2004. Improved exercise capacity and ischemia 6 and 12 months after transendocardial injection of autologous bone marrow mononuclear cells for ischemic cardiomyopathy. Circulation 110(suppl 1):II213-8.nPouly J, Hagège AA, Vilquin JT, et al. 2004. Does the functional efficacy of skeletal myoblast transplantation extend to nonischemic cardiomyopathy? Circulation 110:1626-31.nSalogub TV. 2003. Perspective of embryonic cell transplantation when treating patients with epileptiform neuralgia of peripheric genesis. Transplantology 4:184-5.nSchähinger V, Assmus B, Britten MB, et al. 2004. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI Trial. J Amer Coll Cardiol 44:1690-9.nTaylor DA, Atkins BZ, Hungspreugs P, et al. 1998. Regenerating functional myocardium: improved performance after skeletal myoblast transplantation. Nat Med 4:929-33.nTomita S, Mickle DA, Weisel RD, et al. 2002. Improved heart function with myogenesis and angiogenesis after autologous porcine bone marrow stromal cell transplantation. J Thorac Cardiovasc Surg 123:1132-40.nTouraine JL. 1999. Induction of transplantation tolerance in humans using stem cell transplants prenatally or postnatally. Transplant Proc 31:2735-7.nTsymbalyuk VI, Yaminsky YY. 2003. Usage of embryonic nerve tissue transplantation to improve the conductivity of spinal cord after traumatic damage in animals and humans. Transplantology 4:199-201.nZhang S, Wang D, Estrov Z, Raj S, Willerson JT, Yeh ET. 2004. Both cell fusion and transdifferentiation account for the transformation of human peripheral blood CD34-positive cells into cardiomyocytes in vivo. Circulation 110:3803-7.nZorin MO, Yurchenko TN, Latyshev DY. 2003. Application of cryopreserved suspension of embryonic neuronal cells in combined treatment of patients with ischemic insults of basal ganglias. Transplantology 4:149-50.n

Published

2010-02-11

How to Cite

Benetti, F., Peñherrera, E., Maldonado, T., Vera, Y. D., Subramanian, V., & Geffner, L. (2010). Direct Myocardial Implantation of Human Fetal Stem Cells in Heart Failure Patients: Long-term Results. The Heart Surgery Forum, 13(1), E31-E35. https://doi.org/10.1532/HSF98.20091130

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