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Organogenesis and tissue engineering
Transplant Immunology 12 (2004) 191–192
Editorial
Organogenesis and tissue engineering
In the seventeenth century, William Harvey proved that blood circulates continuously within a closed system. As a logical extension, the first transfusions of blood into animals and from animals into humans were attempted. Given three-plus centuries of hindsight, one could propose that engravings depicting these transfusion techniques (Fig. 1). w1x represent an early depiction of allogeneic and xenogeneic therapy that, while carried out for the purpose of transplanting one organ (terminally differentiated blood cells), effected simultaneously an infusion of stem cells participating in maintenance (organogenesis) and repair (tissue engineering) of others such as kidneys w2x. At any given time there are approximately 100 trillion cells in the human body that divide, differentiate and self-generate over time and space into an auto-engineered system of organs and tissues w3x. The use of exogenous cells or groups of cells for organogenesis and tissue engineering in recapitulation of these events, confers an array of therapeutic advantages relative to the transplantation of whole organs. Thus, (1) cells can be implanted at optimal therapeutic locations including natural sites, immunoprivileged sites or ectopic sites; (2) cells can be manipulated prior to transplantation to enhance their function or reduce their immunogenicity; (3) cells can be banked and cryopreserved; and (4) cells can be combined with different cell types in the same graft or with non-cellular biomaterials w4–6x. Sources for cell replacement can be autologous, allogeneic or xenogeneic. Autologous sources offer advantages of manipulation with minimal risk of adverse host response and disease transmission. Allogeneic sources are more likely to be complicated by the presence of disease-transmitting viruses. Xenogeneic cells are more likely to generate an adverse response from the host w5x. Replacement cells can originate in immortalized cell lines or from totipotent precursors wembryonic stem (ES) cellsx or can be separated from tissues as terminally differentiated components (such as Islets of Langerhans) w6x. Replacements can be uniform groups of cells committed to one or another cell fate, as are fetal myoblasts w6x, or mixed groups programmed to develop into a specific organ, such as a metanephros w7x.
Issues relating to the prospective removal of an organ from one individual and its placement in a second individual evoked a good deal of controversy among scientists, physicians and ethicists when transplantation was in its infancy. Questions about how and when organs could be retrieved from humans who were in the process of dying and whether or not a living donor should be allowed to assume the risks associated with organ donation were actively debated. Today, we discuss how the very limited number of organs should be allocated w8x. The use of cells for organogenesis and tissue engineering raises questions at least as vexing as those than first arose in the context of organ transplantation. They include whether it is justifiable to use animals as a source of cells or tissues for transplantation into humans, whether potential complications and risks that accompany the use of cells and tissues from various sources can ever be adequately conveyed to patients as part of informed consent, and whether the public health is placed at risk by the use of cells or tissues derived from animals w8x, as well as whether health care dollars are wisely spent to develop and implement these technologies. Weighing a risk of undetermined likelihood to the general population, such as the emergence of a new pathogen originating from infection of host human cells with an endogenous retrovirus of animal origin, against the imminent risk of doing nothing for an individual who is desperately in need of replacing an organ for which there are no donors is a formidable task w8x. This ethical quandary along with the other questions posed above, are properly debated by society as a whole and will not be addressed further as such in this special issue of Transplant Immunology. Rather, the special issue of Transplant Immunology will confine itself to describing the technologies themselves. It will catalog new advances in organogenesisy tissue engineering that direct principles of cell transplantation, materials science and bioengineering towards the development of biological substitutes that can restore and maintain normal organ function w9x. More than a dozen different laboratories are represented. Each is engaged in studies designed to establish
0966-3274/04/$ - see front matter 䊚 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.trim.2003.12.018
192
Editorial
Fig. 1. Engravings in Johann Elshotz, Clysmatica Nova (1667) showing a man receiving an infusion in both an arm and a leg, and the techniques of transfusion from animal to man and man to man. Col. Brand., Biblioteque Nationale, Paris.
new means of replacement for functions of organs such as the brain and spinal cord, liver, kidney, heart, musculoskeletal system, pancreas or urogenital system. Today, the work described is at the cutting edge of biomedicine, and many therapeutic concepts it embraces are novel and controversial. No doubt, during the coming decades the tenets of organogenesis and tissue engineering delineated herein will become as familiar to students of the healing arts as the circulation of blood, and many of the techniques will assume a rightful place as part of mainstream clinical practice. References w1x Lyons AS, Petrucelli JR. Medicine, an illustrated history. New York: Harry N. Abrams Inc, 1978. p. 426 –463. w2x Poulsom R. Does bone marrow contain renal precursor cells? Nephron 2003;93(2):e53 –e57. w3x Sipe JD. Tissue engineering and reparative medicine. Ann NY Acad Sci 2002;961:1 –9.
w4x Naughton GK. From lab bench to market: critical issues in tissue engineering. Ann NY Acad Sci 2002;961:372 –385. w5x Edge ASB, Gosse ME, Dinsmore J. Xenogeneic cell therapy: current progress and future developments in porcine cell transplantation. Cell Transplant 1998;7(6):525 –539. w6x Gage FH. Cell Ther Nat 1998;392(Suppl 6679):18 –24. w7x Rogers SA, Lowell JA, Hammerman NA, Hammerman MR. Transplantation of developing metanephroi into adult rats. Kidney Int 1998;54(1):27 –37. w8x Samstein B, Platt J. Physiologic and immunologic hurdles to xenotransplantation. J Am Soc Nephrol 2001;12(1):182 –193. w9x Godbey WT, Atala A. In vitro systems for tissue engineering. Ann NY Acad Sci 2002;961:10 –26. The Guest Editors: Marc R. Hammerman Departments of Medicine, and Cell Biology and Physiology, Washington University School of Medicine, Renal Division, Box 8126, 660 S. Euclid Ave., St. Louis, MO 63110, USA Raffaello Cortesini Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, NY, USA
Editorial
Organogenesis and tissue engineering
In the seventeenth century, William Harvey proved that blood circulates continuously within a closed system. As a logical extension, the first transfusions of blood into animals and from animals into humans were attempted. Given three-plus centuries of hindsight, one could propose that engravings depicting these transfusion techniques (Fig. 1). w1x represent an early depiction of allogeneic and xenogeneic therapy that, while carried out for the purpose of transplanting one organ (terminally differentiated blood cells), effected simultaneously an infusion of stem cells participating in maintenance (organogenesis) and repair (tissue engineering) of others such as kidneys w2x. At any given time there are approximately 100 trillion cells in the human body that divide, differentiate and self-generate over time and space into an auto-engineered system of organs and tissues w3x. The use of exogenous cells or groups of cells for organogenesis and tissue engineering in recapitulation of these events, confers an array of therapeutic advantages relative to the transplantation of whole organs. Thus, (1) cells can be implanted at optimal therapeutic locations including natural sites, immunoprivileged sites or ectopic sites; (2) cells can be manipulated prior to transplantation to enhance their function or reduce their immunogenicity; (3) cells can be banked and cryopreserved; and (4) cells can be combined with different cell types in the same graft or with non-cellular biomaterials w4–6x. Sources for cell replacement can be autologous, allogeneic or xenogeneic. Autologous sources offer advantages of manipulation with minimal risk of adverse host response and disease transmission. Allogeneic sources are more likely to be complicated by the presence of disease-transmitting viruses. Xenogeneic cells are more likely to generate an adverse response from the host w5x. Replacement cells can originate in immortalized cell lines or from totipotent precursors wembryonic stem (ES) cellsx or can be separated from tissues as terminally differentiated components (such as Islets of Langerhans) w6x. Replacements can be uniform groups of cells committed to one or another cell fate, as are fetal myoblasts w6x, or mixed groups programmed to develop into a specific organ, such as a metanephros w7x.
Issues relating to the prospective removal of an organ from one individual and its placement in a second individual evoked a good deal of controversy among scientists, physicians and ethicists when transplantation was in its infancy. Questions about how and when organs could be retrieved from humans who were in the process of dying and whether or not a living donor should be allowed to assume the risks associated with organ donation were actively debated. Today, we discuss how the very limited number of organs should be allocated w8x. The use of cells for organogenesis and tissue engineering raises questions at least as vexing as those than first arose in the context of organ transplantation. They include whether it is justifiable to use animals as a source of cells or tissues for transplantation into humans, whether potential complications and risks that accompany the use of cells and tissues from various sources can ever be adequately conveyed to patients as part of informed consent, and whether the public health is placed at risk by the use of cells or tissues derived from animals w8x, as well as whether health care dollars are wisely spent to develop and implement these technologies. Weighing a risk of undetermined likelihood to the general population, such as the emergence of a new pathogen originating from infection of host human cells with an endogenous retrovirus of animal origin, against the imminent risk of doing nothing for an individual who is desperately in need of replacing an organ for which there are no donors is a formidable task w8x. This ethical quandary along with the other questions posed above, are properly debated by society as a whole and will not be addressed further as such in this special issue of Transplant Immunology. Rather, the special issue of Transplant Immunology will confine itself to describing the technologies themselves. It will catalog new advances in organogenesisy tissue engineering that direct principles of cell transplantation, materials science and bioengineering towards the development of biological substitutes that can restore and maintain normal organ function w9x. More than a dozen different laboratories are represented. Each is engaged in studies designed to establish
0966-3274/04/$ - see front matter 䊚 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.trim.2003.12.018
192
Editorial
Fig. 1. Engravings in Johann Elshotz, Clysmatica Nova (1667) showing a man receiving an infusion in both an arm and a leg, and the techniques of transfusion from animal to man and man to man. Col. Brand., Biblioteque Nationale, Paris.
new means of replacement for functions of organs such as the brain and spinal cord, liver, kidney, heart, musculoskeletal system, pancreas or urogenital system. Today, the work described is at the cutting edge of biomedicine, and many therapeutic concepts it embraces are novel and controversial. No doubt, during the coming decades the tenets of organogenesis and tissue engineering delineated herein will become as familiar to students of the healing arts as the circulation of blood, and many of the techniques will assume a rightful place as part of mainstream clinical practice. References w1x Lyons AS, Petrucelli JR. Medicine, an illustrated history. New York: Harry N. Abrams Inc, 1978. p. 426 –463. w2x Poulsom R. Does bone marrow contain renal precursor cells? Nephron 2003;93(2):e53 –e57. w3x Sipe JD. Tissue engineering and reparative medicine. Ann NY Acad Sci 2002;961:1 –9.
w4x Naughton GK. From lab bench to market: critical issues in tissue engineering. Ann NY Acad Sci 2002;961:372 –385. w5x Edge ASB, Gosse ME, Dinsmore J. Xenogeneic cell therapy: current progress and future developments in porcine cell transplantation. Cell Transplant 1998;7(6):525 –539. w6x Gage FH. Cell Ther Nat 1998;392(Suppl 6679):18 –24. w7x Rogers SA, Lowell JA, Hammerman NA, Hammerman MR. Transplantation of developing metanephroi into adult rats. Kidney Int 1998;54(1):27 –37. w8x Samstein B, Platt J. Physiologic and immunologic hurdles to xenotransplantation. J Am Soc Nephrol 2001;12(1):182 –193. w9x Godbey WT, Atala A. In vitro systems for tissue engineering. Ann NY Acad Sci 2002;961:10 –26. The Guest Editors: Marc R. Hammerman Departments of Medicine, and Cell Biology and Physiology, Washington University School of Medicine, Renal Division, Box 8126, 660 S. Euclid Ave., St. Louis, MO 63110, USA Raffaello Cortesini Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, NY, USA