Cell-Based Therapies for Myocardial Repair: Emerging Role for Bone Marrow-Derived Mesenchymal Stem Cells (MSCs) in the Treatment of the Chronically Injured Heart

  • Jose S. Da Silva
  • Joshua M. Hare
Part of the Methods in Molecular Biology book series (MIMB, volume 1037)


Accumulating data support the use of bone marrow (BM)-derived MSCs in animal models (e.g., swine) to restore cardiac function and tissue perfusion in chronic cardiac injury. Based on results obtained in swine, we are currently conducting phase I/II clinical trials to address the safety, cell type, cell dose, delivery technique, and efficacy of MSCs in patients with chronic heart failure. MSCs for these trials are isolated from harvested BM and then processed and expanded for intracardiac injection. The BM-MSCs in use for the clinical trials are of clinical grade having been processed successfully in an FDA-approved cGMP facility.

Key words




This work is funded by National Institutes Health grants U54-HL081028 (Specialized Center for Cell-Based Therapy), P20-HL101443, and R01-grants HL084275, HL110737-01, HL107110, and HL094849 to Dr. Hare.


  1. 1.
    Ratcliffe E, Thomas RJ, Williams DJ (2011) Current understanding and challenges in bioprocessing of stem cell-based therapies for regenerative medicine. Br Med Bull 100(1):137–155PubMedCrossRefGoogle Scholar
  2. 2.
    Astori G et al (2010) Bone marrow derived stem cells in regenerative medicine as advanced therapy medicinal products. Am J Transl Res 2(3):285–295PubMedCentralPubMedGoogle Scholar
  3. 3.
    Bach FH et al (1968) Bone-marrow transplantation in a patient with the Wiskott-Aldrich syndrome. Lancet 2(7583):1364–1366PubMedCrossRefGoogle Scholar
  4. 4.
    Gatti RA et al (1968) Immunological reconstitution of sex-linked lymphopenic immunological deficiency. Lancet 2(7583):1366–1369PubMedCrossRefGoogle Scholar
  5. 5.
    Deans RJ, Moseley AB (2000) Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol 28(8):875–884PubMedCrossRefGoogle Scholar
  6. 6.
    Williams AR et al (2011) Intramyocardial stem cell injection in patients with ischemic cardiomyopathy: functional recovery and reverse remodeling. Circ Res 108(7):792–796PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Kemp KC, Hows J, Donaldson C (2005) Bone marrow-derived mesenchymal stem cells. Leuk Lymphoma 11(46):1531–1544CrossRefGoogle Scholar
  8. 8.
    Togel F, Westenfelder C (2007) Adult bone marrow-derived stem cells for organ regeneration and repair. Dev Dyn 236(12):3321–3331PubMedCrossRefGoogle Scholar
  9. 9.
    Biehl JK, Russell B (2009) Introduction to stem cell therapy. J Cardiovasc Nurs 24(2):98–103PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Boyle AJ, McNiece IK, Hare JM (2010) Mesenchymal stem cell therapy for cardiac repair. Methods Mol Biol 660:65–84PubMedCrossRefGoogle Scholar
  11. 11.
    Husnain K, Haider MA (2004) Bone marrow cell transplantation in clinical perspective. J Mol Cell Cardiol 38:225–235Google Scholar
  12. 12.
    Muller YD et al (2011) Transplantation tolerance: clinical potential of regulatory T cells. Self Nonself 2(1):26–34PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Christoforou N, Gearhart JD (2007) Stem cells and their potential in cell-based cardiac therapies. Prog Cardiovasc Dis 49(9):396–413PubMedCrossRefGoogle Scholar
  14. 14.
    Kajstura J et al (2005) Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion. Circ Res 96(1):127–137PubMedCrossRefGoogle Scholar
  15. 15.
    Nunes SS et al (2011) Stem cell-based cardiac tissue engineering. J Cardiovasc Transl Res 4(5):592–602PubMedCrossRefGoogle Scholar
  16. 16.
    Kanashiro-Takeuchi RM, Schulman IH, Hare JM (2011) Pharmacologic and genetic strategies to enhance cell therapy for cardiac regeneration. J Mol Cell Cardiol 51(4):619–625PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Schuleri KH et al (2009) Autologous mesenchymal stem cells produce reverse remodelling in chronic ischaemic cardiomyopathy. Eur Heart J 30(22):2722–2732PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
  19. 19.
    Hare JM (2009) Translational development of mesenchymal stem cell therapy for cardiovascular diseases. Tex Heart Inst J 36(2):145–147PubMedCentralPubMedGoogle Scholar
  20. 20.
    U.S. Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research (2008) Guidance for FDA reviewers and sponsors. Content and review of chemistry, manufacturing, and control (CMC) information for human somatic cell therapy investigational new drug applications (INDs)Google Scholar
  21. 21.
    CFR 312.23(a)(7)(iv)(b)Google Scholar
  22. 22.
  23. 23.
    CFR 113.53Google Scholar
  24. 24.
    CFR 211.84(a)Google Scholar
  25. 25.
    CFR 610.12Google Scholar
  26. 26.
    United States Pharmacopeia (USP) <71 > Sterility testsGoogle Scholar
  27. 27.
    CBER (1993) Points to consider in the characterization of cell lines used to produce biologicalsGoogle Scholar
  28. 28.
    CFR 600.3(r)Google Scholar
  29. 29.
    CFR 610.13Google Scholar
  30. 30.
  31. 31.
    FDA (1987) FDA guideline on validation of the Limulus Amebocyte Lysate (LAL) Test as end-product endotoxin test for human and animal parenteral drugs, biological products, and medical devicesGoogle Scholar
  32. 32.
    CFR 312.23(a)(7)(ii)Google Scholar
  33. 33.
    CFR 1271.290(b)Google Scholar
  34. 34.
    CFR 312.6(a)Google Scholar
  35. 35.
    CFR 1271.250Google Scholar
  36. 36.
    CFR 1271.90Google Scholar
  37. 37.
    FDA (1999) Guidance for industry: container closure systems for packaging human drugs and biologics; chemistry, manufacturing, and controls documentation, May 1999Google Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Jose S. Da Silva
    • 1
  • Joshua M. Hare
    • 1
  1. 1.University of MiamiMiamiUSA

Personalised recommendations