Autologous Cell Therapy: Current Treatments and Future Prospects
- 0 Comments
- 15166 reads
Relatively safe, a segment of healthy vessel is harvested from either the leg (saphenous vein), from the inside of the breast (internal mammary artery), or from the forearm (radial artery), which is used to connect the aorta and the coronary artery beyond the blockages. High success rates can mostly be attributed to the autologous nature of the transplant. Such results have inspired work for further autologous treatments.
Due to a population of mainly terminally differentiated myocytes and an insufficient regenerative response, the adult heart is rendered inept to fully repopulate any reduced cardiomyocyte levels after, for example, a myocardial infarction.23,24 Autologous treatments available involve taking skeletal muscle from the patient’s back or abdomen to be enveloped over the weak heart, and subsequently using a device similar to a pacemaker, to electrically stimulate the transplant.
Autologous cells can also be transplanted to aid an ailing heart and involve the use of bone marrow derived stem cells or skeletal myoblasts. Although such work is still undergoing clinical examination, the aim is to replace the damaged myocardium or to assist in the healing process.25–28 Many practical considerations regarding cell therapy remain, such as the timing of transplant into the post infarct heart, whether the patient is fit to undergo surgery, and the method of cell delivery (injection into the coronary sinus, artery or directly into the damaged myocardium).29 The advantage of using skeletal myoblasts over other cell types is that they can be obtained from muscle with relatively little stress put upon the patient after heart trauma. The harvest of hematopoietic stem cells, on the other hand, requires numerous painful bone marrow biopsies that may be questionable in the days or even weeks following a major heart attack. The long-term outcomes of these transplants have yet to be assessed, as this form of treatment is in its developmental phase. However, as with any heart surgery, there are associated risks of arrhythmia, cardiac arrest, pain, or death.
Advances in the potential of stem cells to induce tissue regeneration and neovascularization has increased interest for use in treatment of cardiovascular diseases.30,31 The injection of autologous mononuclear bone marrow cells into areas of ischemic myocardium has been shown to improve the condition of a patient during phase I clinical trials.10,11,30 Moreover, tissue engineering uses a defined and specific cell population cultivated for a purpose, and therefore, unlike surgical reconstruction using other body tissues, these cultivated tissues can reinstate lost function to a better degree. Effectively, these cells can also be cultivated and combined with gene therapy, removing or rectifying deficient genes to correct the operative defect.
Commercially Available Autologous Treatments
Examples of commercially available autologous treatments are discussed throughout this review (Tables 1, 2). This section briefly discusses two such successful treatments. Commercially available since 1987, epidermal autografts consisting of autologous keratinocytes co-cultured with irradiated murine cells has been on the market (Epicel®, Genzyme Biosurgery, Cambridge, MA).32,33 Successful treatment and coverage of large burn wounds has been reported (Table 1). In 1997, the US Food and Drug Administration (FDA) approved a product consisting of autologous cultured chondrocytes (Carticel®, Genzyme Biosurgery).
1. Weise RA, Mannis MJ, Vastine DW, Fujikawa LS, Roth AM. Conjunctival transplantation. Autologous and homologous grafts. Arch Ophthalmol. 1985;103(11):1736–1740.
2. Napoli C, Williams-Ignarro S, de Nigris F, et al. Beneficial effects of concurrent autologous bone marrow cell therapy and metabolic intervention in ischemia-induced angiogenesis in the mouse hindlimb. Proc Natl Acad Sci U S A. 2005;102(47):17202–17206.
3. Bertho JM, Frick J, Prat M, et al. Comparison of autologous cell therapy and granulocyte-colony stimulating factor (G-CSF) injection vs. G-CSF injection alone for the treatment of acute radiation syndrome in a non-human primate model. Int J Radiat Oncol Biol Phys. 2005;63(3):911–920.
4. Bertho JM, Prat M, Frick J, Demarquay C, et al. Application of autologous hematopoietic cell therapy to a nonhuman primate model of heterogeneous high-dose irradiation. Radiat Res. 2005;163(5):557–570.
5. Bang OY, Lee JS, Lee PH, Lee G. Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol. 2005;57(6):874–882.
6. Dharmasaroja P. Bone marrow-derived mesenchymal stem cells for the treatment of ischemic stroke. J Clin Neurosci. 2009;16(1):12–20.
7. Perin EC. The use of stem cell therapy for cardiovascular disease. Tex Heart Inst J. 2005;32(3):390–392.
8. Perin EC, Dohmann HF, Borojevic R, et al. Improved exercise capacity and ischemia 6 and 12 months after transendocardial injection of autologous bone marrow mononuclear cells for ischemic cardiomyopathy. Circulation. 2004;110(11 Suppl 1):II213–II218.
9. Perin E. Transendocardial injection of autologous mononuclear bone marrow cells in end-stage ischemic heart failure patients: one-year follow-up. Int J Cardiol. 2004;95(Suppl 1):S45–S46.
10. Slavin S. Allogeneic cell-mediated immunotherapy at the stage of minimal residual disease following high-dose chemotherapy supported by autologous stem cell transplantation. Acta Haematol. 2005;114(4):214–220.
11. Becker PS. The current status of gene therapy in autologous transplantation. Acta Haematol. 2005;114(4):188–197.
12. Sadelain M, Rivella S, Lisowski L, Samakoglu S, Rivière I. Globin gene transfer for treatment of the beta-thalassemias and sickle cell disease. Best Pract Res Clin Haematol. 2004;17(3):517–534.
13. Tyndall A, Daikeler T. Autologous hematopoietic stem cell transplantation for autoimmune diseases. Acta Haematol. 2005;114(4):239–247.
14. Alexander T, Thiel A, Rosen O, et al. Depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induces long-term remission through de novo generation of a juvenile and tolerant immune system. Blood. 2009;113(1):214–223.
15. Knoller N, Auerbach G, Fulga V, et al. Clinical experience using incubated autologous macrophages as a treatment for complete spinal cord injury: phase I study results. J Neurosurg Spine. 2005;3(3):173–181.
16. Schwartz M, Yoles E. Macrophages and dendritic cells treatment of spinal cord injury: from the bench to the clinic. Acta Neurochir Suppl. 2005;93:147–150.
17. Assina R, Sankar T, Theodore N, et al. Activated autologous macrophage implantation in a large-animal model of spinal cord injury. Neurosurg Focus. 2008;25(5):E3.
18. Gervais A, Bouet-Toussaint F, Toutirais O, De La Pintiere CT, Genetet N, Catros-Quemener V. Ex vivo expansion of antitumor cytotoxic lymphocytes with tumor-associated antigen-loaded dendritic cells. Anticancer Res. 2005;25(3B):2177–2185.
19. Delirezh N, Moazzeni SM, Shokri F, Shokrgozar MA, Atri M, Kokhaei P. Autologous dendritic cells loaded with apoptotic tumor cells induce T cell-mediated immune responses against breast cancer in vitro. Cell Immunol. 2009;257(1–2):23–31.
20. Nakagawa T, Ito J. Cell therapy for inner ear diseases. Curr Pharm Des. 2005;11(9):1203–1207.
21. Liu L, Hartwig D, Harloff S, Herminghaus P, Wedel T, Geerling G. An optimised protocol for the production of autologous serum eyedrops. Graefes Arch Clin Exp Ophthalmol. 2005;243(7):706–714.
22. Watson D, Keller GS, Lacombe V, Fodor PB, Rawnsley J, Lask GP. Autologous fibroblasts for treatment of facial rhytids and dermal depressions. A pilot study. Arch Facial Plast Surg. 1999;1(3):165–170.
23. Taylor DA. Cellular cardiomyoplasty with autologous skeletal myoblasts for ischemic heart disease and heart failure. Curr Control Trials Cardiovasc Med. 2001;2(5):208–210.
24. Torella D, Ellison GM, Nadal-Ginard B, Indolfi C. Cardiac stem and progenitor cell biology for regenerative medicine. Trends Cardiovasc Med. 2005;15(6):229–236.
25. Atkins BZ, Hueman MT, Meuchel J, Hutcheson KA, Glower DD, Taylor DA. Cellular cardiomyoplasty improves diastolic properties of injured heart. J Surg Res. 1999;85(2):234–242.
26. Miyagawa S, Matsumiya G, Funatsu T, et al. Combined autologous cellular cardiomyoplasty using skeletal myoblasts and bone marrow cells for human ischemic cardiomyopathy with left ventricular assist system implantation: report of a case. Surg Today. 2009;39(2):133–136.
27. Lyon A, Harding S. The potential of cardiac stem cell therapy for heart failure. Curr Opin Pharmacol. 2007;7(2):164–170.
28. Menasché P, Alfieri O, Janssens S, et al. The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation. Circulation. 2008;117(9):1189–1200.
29. Tran N, Marie PY, Nloga J, et al. Autologous cell based therapy for treating chronic infarct myocardium. Clin Hemorheol Microcirc. 2005;33(3):263–268.
30. Tayyareci Y, Umman B, Sezer M, et al. Intracoronary autologous bone marrow-derived stem cell transplantation in patients with ischemic cardiomyopathy: results of 18-month follow-up. Turk Kardiyol Dern Ars. 2008;36(8):519–529.
31. Orlic D, Kajstura J, Chimenti S, Bodine DM, Leri A, Anversa P. Bone marrow stem cells regenerate infarcted myocardium. Pediatr Transplant. 2003;7(Suppl 3):86–88.
32. Carsin H, Ainaud P, Le Bever H, et al. Cultured epithelial autografts in extensive burn coverage of severely traumatized patients: a five-year single-center experience with 30 patients. Burns. 2000;26(4):379–387.
33. Wright KA, Nadire KB, Busto P, Tubo R, McPherson JM, Wentworth BM. Alternative delivery of keratinocytes using a polyurethane membrane and the implications for its use in the treatment of full-thickness burn injury. Burns. 1998;24(1):7–17.
34. Cancedda R, Dozin B, Giannoni P, Quarto R. Tissue engineering and cell therapy of cartilage and bone. Matrix Biol. 2003;22(1):81–91.
35. Schindler OS. Cartilage repair using autologous chondrocyte implantation techniques. J Perioper Pract. 2009;19(2):60–64.
36. Erggelet C, Sittinger M, Lahm A. The arthroscopic implantation of autologous chondrocytes for the treatment of full-thickness cartilage defects of the knee joint. Arthroscopy. 2003;19(1):108–110.
37. Sugaya K. Possible use of autologous stem cell therapies for Alzheimer's disease. Curr Alzheimer Res. 2005;2(3):367–376.
38. Tuszynski MH, Smith DE, Roberts J, McKay H, Mufson E. Targeted intraparenchymal delivery of human NGF by gene transfer to the primate basal forebrain for 3 months does not accelerate beta-amyloid plaque deposition. Exp Neurol. 1998;154(2):573–582.
39. Schmitt TL, Steger MM, Pavelka M, Grubeck-Loebenstein B. Interactions of the Alzheimer beta amyloid fragment (25-35) with peripheral blood dendritic cells. Mech Ageing Dev. 1997;94(1–3):223–232.
40. Blesch A, Tuszynski M. Ex vivo gene therapy for Alzheimer's disease and spinal cord injury. Clin Neurosci. 1995;3(5):268–274.
41. Tuszynski MH, Thal L, Pay M, et al. A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease. Nat Med. 2005;11(5):551–555.
42. Burt RK, Cohen BA, Russell E, et al. Hematopoietic stem cell transplantation for progressive multiple sclerosis: failure of a total body irradiation-based conditioning regimen to prevent disease progression in patients with high disability scores. Blood. 2003;102(7):2373–2378.
43. Blanco Y, Saiz A, Carreras E, Graus F. Autologous haematopoietic-stem-cell transplantation for multiple sclerosis. Lancet Neurol. 2005;4(1):54–63.
44. Mancardi G. Further data on autologous haemopoietic stem cell transplantation in multiple sclerosis. Lancet Neurol. 2009;8(3):219–221.
45. Saccardi R, Mancardi GL, Solari A, et al. Autologous HSCT for severe progressive multiple sclerosis in a multicenter trial: impact on disease activity and quality of life. Blood. 2005;105(6):2601–2607.
46. Arnhold S, Semkova I, Andressen C, et al. Iris pigment epithelial cells: a possible cell source for the future treatment of neurodegenerative diseases. Exp Neurol. 2004;187(2):410–417.
47. Edmonds M, Bates M, Doxford M, Gough A, Foster A. New treatments in ulcer healing and wound infection. Diabetes Metab Res Rev. 2000;16(Suppl 1):S51–S54.
48. O’Connor NE, Mulliken JB, Banks-Schlegel S, Kehinde O, Green H. Grafting of burns with cultured epithelium prepared from autologous epidermal cells. Lancet. 1981;317(8211):75–78.
49. Wisser D, Steffes J. Skin replacement with a collagen based dermal substitute, autologous keratinocytes and fibroblasts in burn trauma. Burns. 2003;29(4):375–380.
50. Morimoto N, Saso Y, Tomihata K, et al. Viability and function of autologous and allogeneic fibroblasts seeded in dermal substitutes after implantation. J Surg Res. 2005;125(1):56–67.
51. Zhang X, Deng Z, Wang H, et al. Expansion and delivery of human fibroblasts on micronized acellular dermal matrix for skin regeneration. Biomaterials. 2009;30(14):2666–2674.
52. Homicz MR, Watson D. Review of injectable materials for soft tissue augmentation. Facial Plast Surg. 2004;20(1):21–29.
53. Hanke CW, Thomas JA, Lee WT, Jolivette DM, Rosenberg MJ. Risk assessment of polymyositis/dermatomyositis after treatment with injectable bovine collagen implants. J Am Acad Dermatol. 1996;34(3):450–454.
54. Hanke CW, Higley HR, Jolivette DM, Swanson NA, Stegman SJ. Abscess formation and local necrosis after treatment with Zyderm or Zyplast collagen implant. J Am Acad Dermatol. 1991;25(2 Pt 1):319–326.
55. Robinson JK, Hanke CW. Injectable collagen implant: histopathologic identification and longevity of correction. J Dermatol Surg Oncol. 1985;11(2):124–130.
56. Hanke CW, Robinson JK. Injectable collagen implants. Arch Dermatol. 1983;119(6):533–534.
57. Goode RL. Current status of “soft” implant materials for the face. Arch Facial Plast Surg. 1999;1(1):60–61.
58. Teumer J, Cooley J. Follicular cell implantation: an emerging cell therapy for hair loss. Semin Plast Surg. 2005;19(2):193–200.
59. Njoo MD, Westerhof W. Vitiligo. Pathogenesis and treatment. Am J Clin Dermatol. 2001;2(3):167–181.
60. Boland T, Mironov V, Gutowska A, Roth EA, Markwald RR. Cell and organ printing 2: fusion of cell aggregates in three-dimensional gels. Anat Rec A Discov Mol Cell Evol Biol. 2003;272(2):497–502.
61. Wilson WC Jr, Boland T. Cell and organ printing 1: protein and cell printers. Anat Rec A Discov Mol Cell Evol Biol. 2003;272(2):491–496.
62. Mironov V, Boland T, Trusk T, Forgacs G, Markwald RR. Organ printing: computer-aided jet-based 3D tissue engineering. Trends Biotechnol. 2003;21(4):157–161.
63. Altorjay A, Kiss J, Paál B, et al. The place of gastro-jejuno-duodenal interposition following limited esophageal resection. Eur J Cardiothorac Surg. 2005;28(2):296–300.
64. Cense HA, Visser MR, van Sandick JW, et al. Quality of life after colon interposition by necessity for esophageal cancer replacement. J Surg Oncol. 2004;88(1):32–38.