Autologous Cell Therapy: Current Treatments and Future Prospects
- 9/15/2009
- 0 Comments
- 15159 reads
Abstract: Autologous cell therapy (ACT) is a novel therapeutic intervention that uses an individual’s cells, which are cultured and expanded outside the body, and reintroduced into the donor. Advantages of such an approach include the minimization of risks from systemic immunological reactions, bio-incompatibility, and disease transmission associated with grafts or cells not cultivated from the individual. So far, this form of therapy has been used successfully to bioengineer skin substitutes, aid wound healing, counteract chronic inflammation, treat burns and pressure ulcers, and improve postoperative healing. The authors will review the promising outcomes of various therapeutic interventions using ACT, as well as the concerns raised with using explanted material, and any potential alteration through the cultivation process. This review will discuss its role in assisting the healing process of conditions such as a damaged myocardium, developing hyaline cartilage, and in the treatment of neurodegenerative diseases and other ailments that benefit from the immediate availability of a donor. The use of ACT for cosmetic enhancement or corrective surgery is also gaining recognition as a creditable form of treatment and has been shown to reduce the risk of rejection and to have longer lasting effects than conventional treatments. This form of treatment is under intense investigation with the hope that it will eventually be able to replace conventional forms of plastic surgery to improve the repair process of aging or damaged tissues.
Address correspondence to:
Batool Kazmi, PhD
Eastman Dental Institute
University College of London
256 Gray’s Inn Road
London WC1X 8LD
Phone: 079 4046 0423
Email: batoolkazmi40@hotmail.com
Over the past few decades, since the bioengineering revolution, autologous cell therapy (ACT) has become a rapidly evolving field. From the discovery of plasmids as vectors for bulk protein cultivation in 1973, and the production of recombinant human insulin in 1978, to the construction of the world’s first artificial cornea in 1999, biosynthetic ailments to human conditions have been of great revelation and interest in the scientific industry.
One of the greatest success stories of modern medicine has been the advent of organ transplantation. As life expectancy in the developed world increases, the expiration of body tissues and organs through attrition, disease, or even trauma, is inevitable. Despite its ability to either restore a normal standard of living or extend life, organ transplantation is plagued with its fair share of problems. Almost a victim of its own success, the body’s immune system can sometimes recognize the foreign entity and reject the new tissue or organ regardless of patient matching and immunosuppressive drugs. Such consequences and shortages in supply have increased interest in regenerative and autologous therapies.
Although many cells respond to signaling and stimuli in the body, they can also be cultivated outside the human body in Petri dishes and culture flasks. Tissue engineering techniques allow cell types to be grown in isolation using defined media for optimal growth. Such a capacity allows for the culture and study of cells more closely and independently of the organ from which they are a part. More impressively, this enables a small number of cells taken from an individual to be expanded outside the body and reintroduced into the donor for therapeutic intervention.
Autologous cell therapy is composed of various technologies and disciplines ranging from cellular and molecular biology to virology; however, this review will focus primarily upon cell and tissue based therapies.
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.
_sm.jpg)
Post new comment