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Journal of Cancer Epidemiology & Treatment
Where do we stand on Organ Printing?
Marcel W. Laughton, Joachim Storsberg, Christian Schmidt*
Fraunhofer-Institute Applied Polymer Research (IAP)
www.verizonaonlinepublishing.com
J Can Epi Treat 1(1). Page | 2
*Corresponding author: Christian Schmidt, PhD, Dept. of Polymers for Biomedical Engineering, Fraunhofer-Institute Applied Polymer
Research (IAP), GeiselbergstraBe 69, 14476 Potsdam-Golm, Germany, Tel: +49-331-568-1456; Fax: +49-331-568-3000
E-mail: christian.schmidt@iap.fraunhofer.de
Article Type: Editorial, Submission Date: 05 May 2015, Accepted Date: 10 June 2015, Published Date: 19 June 2015.
Citation: Marcel W. Laughton, Joachim Storsberg and Christian Schmidt (2015) Where do we stand On Organ Printing?. J Can Epi Treat
1(1): 2-3.
Copyright: © 2015 Christian Schmidt, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are
credited.
Vol: 1, Issue: 1
Abstract
Attitude towards organ donation and the risks associated with
organ transplantation drive the search for alternatives. One such
alternative, albeit a conceptual level, could be the generation of an
organ replacement in a controlled setting. For instance, growing
suitable cells onto a printed matrix under appropriate conditions
would then lead to the formation of a functional organ. How
about the practical issues surrounding either duplication or de
novo generation of an organ with, say, a device to print a suitable
matrix and grow and differentiate cells on it? Here, we wish to
outline selected safety-related questions arising from the ex vivo
growth, differentiation and maintenance of cells or cell systems.
Keywords: Cancer biology, organ printing, transplantation
Introduction
Many people associate the term “Trojan” with myths surrounding
military tactics. As a backdrop, the city of Troy could not be
conquered by the Greeks because of their unshaken stronghold.
So, the Greek soldiers decided to infiltrate the fortress by a
“Trojan horse”, which carried Greek soldiers. This way, they were
able to win this war from within the city of Troy. Aside from
the historical context, Trojan Horses are now associated with
malware that infiltrates and damages computer systems. These
two instances are used to argue in favor of the opinion that the
phrase “Trojan entity” is used to describe unfavorable features of
a particular object.
Assuring continued patient’s safety and wellbeing are lynchpins
of the medical profession. Thus, safety, efficacy and reliability
throughout the life cycle of devices for their intended clinical
use leaves no room for doubt that features resembling “Trojan
entities” are to be assiduously avoided in the development and
refinement of implants, to name one out of many examples of
devices used in clinical settings.
With citizens benefiting from technological advances by
extending quality and duration of life, leaving non-natural causes
of demise, such as violence and catastrophic events, aside, the
issue of an increased demand for readily available transplantation
material cannot be neglected. This, among many others, fuels
the attempt of separating transplantation medicine from socio-
ethical challenges associated with organ donation.
Discussion
One approach to reach this goal might be to use the technology
of the 3D-Printer [1,2]. Its technical advance could possibly
generate synthetic parts of the body, which could be liked as a
matrix to support natural processes (see [3] for further reading
on notions pertaining to morphogenetic fields). As for bone
matrices, osteoblasts contribute to the synthesis of bone matrix,
and the printed biomaterial could be likened as a platform for
bone repair.
As for the generation of a matrix for organ transplant,
extracellular matrix material, such as collagen, is reported to be
used in a clinical setting although the patient who received the
cultured skin auto-graft declined follow-up studies, as reported
by Zöller et al. [4] . Credence for this notion comes from a series
of successful studies where solubilized collagen served as carrier
for the skin graft used [5,6].
Published evidence argues persuasively in favor of the notion
that cells react to a removal from their natural environment, e.g.
the tissue inside the body, to an artificial environment, such as a
culture dish with medium inside an incubator oven. Depending
on the condition, immortalization and tumorigenic potential
may occur.
For illustration, the tumorigenic transformation of a cell is
selected, and classical papers are referenced to show selected
lines of understanding and implications of the reported studies:
Hayflick [7] described a limited number of population doublings
of human diploid cells in an ex vivo setting. In agreement with
earlier publications [8,9], where the induction of the proto-
oncogene c-jun by serum is described, Takahashi et al. [10] report
a spontaneous immortalization and malignant transformation
of primary, human endothelial cells after prolonged culture in
serum- containing growth medium. This immortalization, or,
in other words, continuous progression through the cell cycle,
appears to involve negative p53 regulation [11]. Note that these
observations tie in nicely with the hypothesis that a ‘multiple
hits’ lead a healthy cells onto the oncogenic path [12,13].
Some cells go through this crisis without any alteration in
their metabolism and/or programming and others do not.
Furthermore, the possibility of a malignant transformation by
other factors or their influence on the balance of physiological
J Can Epi Treat 1(1). Page | 3
processescannotbeneglected.Twoexamplesarecitedtoillustrate
the point: Border and Ruoslahti and Minton [14,15], as well as
the references therein, illustrate a light and dark side of TGF-b,
whereas Switzer et al, Larocque et al, and LeBreton et al. [16-
18]provide excellent reading regarding current understanding
of the biology of primate T-lymphotropic viruses and associated
oncogenic events after infection of target cells occurred.
Conclusion
Would it be possible to create ideal biomaterials that are
compatible to our highly complex body? Safety considerations,
such as the risk of malignant transformation of cells in, say, an
ex vivo culture setting and/or the combination of soluble factors
used to supplement growth media cannot be neglected. This
question of patient safety must be addressed.
Citation: Marcel W. Laughton, Joachim Storsberg and Christian Schmidt (2015) Where do we stand On Organ Printing?. J Can Epi Treat 1(1): 2-3.
References
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Reiffel AJ, Kafka C, Hernandez KA, Popa S, Perez JL, Zhou S, et al.2.	
High-fidelity tissue engineering of patient-specific auricles for
reconstruction of pediatric microtia and other auricular deformities.
PLoS One. 2013; 8(2):e56506. doi: 10.1371/journal.pone.0056506.
Levin M. The wisdom of the body: future techniques and approaches3.	
to morphogenetic fields in regenerative medicine, developmental
biology and cancer. Regen Med. 2011; 6(6):667-673. doi: 10.2217/
rme.11.69.
Zöller N, Valesky E, Butting M, Hofmann M, Kippenberger S,4.	
Bereiter Hahn J, et al. Clinical application of a tissue-cultured
skin autograft: an alternative for the treatment of non-healing or
slowly healing wounds? Dermatology. 2014; 229(3):190-198. doi:
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MorimotoN,ItoT,TakemotoS,KatakamiM,KandaN,TadaH,etal.An5.	
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fibroblast-seeded artificial skin cultured with animal product-free
medium in patients with diabetic foot ulcers. Int Wound J. 2014;
11(2):183-189. doi: 10.1111/j.1742-481X.2012.01064.x.
Suzuki S, Morimoto N, Yamawaki S, Fujitaka J, Kawai K. A case of6.	
giant naevus followed up for 22 years after treatment with artificial
dermis. J Plast Reconstr Aesthet Surg. 2013; 66(8):e229-233. doi:
10.1016/j.bjps.2013.03.018.
Hayflick L. The limited in vitro lifetime of human diploid cell strains.7.	
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Angel P, Hattori K, Smeal T, Karin M. The jun proto-oncogene is8.	
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transformation and immortalization of human endothelial cells. In
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Schreiber M, Kolbus A, Piu F, Szabowski A, Möhle-Steinlein U, Tian J.11.	
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Dev. 1999; 13(5):607-619.
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carcinogenesis. Carcinogenesis. 2000; 21(3):477-484.
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disease: the dark side of tissue repair. J Clin Invest. 1992; 90(1):1-7.
doi: 10.1172/JCI115821.
Minton K. Tumour immunology: TGF beta betrays immunity15.	
for tumorigenesis. Nat Rev Immunol. 2008; 8:89. doi:10.1038/
nri2263.
Switzer WM, Salemi M, Qari SH, Jia H, Gray RR, Katzourakis A, et al.16.	
Ancient, independent evolution and distinct molecular features of
the novel human T-lymphotropic virus type 4. Retrovirology. 2009;
6:9. doi: 10.1186/1742-4690-6-9.
Larocque É, André-Arpin C, Borowiak M, Lemay G, Switzer WM,17.	
Duc Dodon M, et al. Human T-cell leukemia virus type 3 (HTLV-3)
and HTLV-4 antisense-transcript-encoded proteins interact and
transactivate Jun family-dependent transcription via their atypical
bZIP motif. J Virol. 2014;88(16):8956-8970.doi: 10.1128/JVI.01094-
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emi.2014.7.

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JournalofCancerEpidemiologyandTreatment2

  • 1. Journal of Cancer Epidemiology & Treatment Where do we stand on Organ Printing? Marcel W. Laughton, Joachim Storsberg, Christian Schmidt* Fraunhofer-Institute Applied Polymer Research (IAP) www.verizonaonlinepublishing.com J Can Epi Treat 1(1). Page | 2 *Corresponding author: Christian Schmidt, PhD, Dept. of Polymers for Biomedical Engineering, Fraunhofer-Institute Applied Polymer Research (IAP), GeiselbergstraBe 69, 14476 Potsdam-Golm, Germany, Tel: +49-331-568-1456; Fax: +49-331-568-3000 E-mail: christian.schmidt@iap.fraunhofer.de Article Type: Editorial, Submission Date: 05 May 2015, Accepted Date: 10 June 2015, Published Date: 19 June 2015. Citation: Marcel W. Laughton, Joachim Storsberg and Christian Schmidt (2015) Where do we stand On Organ Printing?. J Can Epi Treat 1(1): 2-3. Copyright: © 2015 Christian Schmidt, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Vol: 1, Issue: 1 Abstract Attitude towards organ donation and the risks associated with organ transplantation drive the search for alternatives. One such alternative, albeit a conceptual level, could be the generation of an organ replacement in a controlled setting. For instance, growing suitable cells onto a printed matrix under appropriate conditions would then lead to the formation of a functional organ. How about the practical issues surrounding either duplication or de novo generation of an organ with, say, a device to print a suitable matrix and grow and differentiate cells on it? Here, we wish to outline selected safety-related questions arising from the ex vivo growth, differentiation and maintenance of cells or cell systems. Keywords: Cancer biology, organ printing, transplantation Introduction Many people associate the term “Trojan” with myths surrounding military tactics. As a backdrop, the city of Troy could not be conquered by the Greeks because of their unshaken stronghold. So, the Greek soldiers decided to infiltrate the fortress by a “Trojan horse”, which carried Greek soldiers. This way, they were able to win this war from within the city of Troy. Aside from the historical context, Trojan Horses are now associated with malware that infiltrates and damages computer systems. These two instances are used to argue in favor of the opinion that the phrase “Trojan entity” is used to describe unfavorable features of a particular object. Assuring continued patient’s safety and wellbeing are lynchpins of the medical profession. Thus, safety, efficacy and reliability throughout the life cycle of devices for their intended clinical use leaves no room for doubt that features resembling “Trojan entities” are to be assiduously avoided in the development and refinement of implants, to name one out of many examples of devices used in clinical settings. With citizens benefiting from technological advances by extending quality and duration of life, leaving non-natural causes of demise, such as violence and catastrophic events, aside, the issue of an increased demand for readily available transplantation material cannot be neglected. This, among many others, fuels the attempt of separating transplantation medicine from socio- ethical challenges associated with organ donation. Discussion One approach to reach this goal might be to use the technology of the 3D-Printer [1,2]. Its technical advance could possibly generate synthetic parts of the body, which could be liked as a matrix to support natural processes (see [3] for further reading on notions pertaining to morphogenetic fields). As for bone matrices, osteoblasts contribute to the synthesis of bone matrix, and the printed biomaterial could be likened as a platform for bone repair. As for the generation of a matrix for organ transplant, extracellular matrix material, such as collagen, is reported to be used in a clinical setting although the patient who received the cultured skin auto-graft declined follow-up studies, as reported by Zöller et al. [4] . Credence for this notion comes from a series of successful studies where solubilized collagen served as carrier for the skin graft used [5,6]. Published evidence argues persuasively in favor of the notion that cells react to a removal from their natural environment, e.g. the tissue inside the body, to an artificial environment, such as a culture dish with medium inside an incubator oven. Depending on the condition, immortalization and tumorigenic potential may occur. For illustration, the tumorigenic transformation of a cell is selected, and classical papers are referenced to show selected lines of understanding and implications of the reported studies: Hayflick [7] described a limited number of population doublings of human diploid cells in an ex vivo setting. In agreement with earlier publications [8,9], where the induction of the proto- oncogene c-jun by serum is described, Takahashi et al. [10] report a spontaneous immortalization and malignant transformation of primary, human endothelial cells after prolonged culture in serum- containing growth medium. This immortalization, or, in other words, continuous progression through the cell cycle, appears to involve negative p53 regulation [11]. Note that these observations tie in nicely with the hypothesis that a ‘multiple hits’ lead a healthy cells onto the oncogenic path [12,13]. Some cells go through this crisis without any alteration in their metabolism and/or programming and others do not. Furthermore, the possibility of a malignant transformation by other factors or their influence on the balance of physiological
  • 2. J Can Epi Treat 1(1). Page | 3 processescannotbeneglected.Twoexamplesarecitedtoillustrate the point: Border and Ruoslahti and Minton [14,15], as well as the references therein, illustrate a light and dark side of TGF-b, whereas Switzer et al, Larocque et al, and LeBreton et al. [16- 18]provide excellent reading regarding current understanding of the biology of primate T-lymphotropic viruses and associated oncogenic events after infection of target cells occurred. Conclusion Would it be possible to create ideal biomaterials that are compatible to our highly complex body? Safety considerations, such as the risk of malignant transformation of cells in, say, an ex vivo culture setting and/or the combination of soluble factors used to supplement growth media cannot be neglected. This question of patient safety must be addressed. Citation: Marcel W. Laughton, Joachim Storsberg and Christian Schmidt (2015) Where do we stand On Organ Printing?. J Can Epi Treat 1(1): 2-3. References Mironov V, Boland T, Trusk T, Forgacs G, Markwald RR. Organ printing:1. computer-aided jet-based 3D tissue engineering. Trends Biotechnol. 2003; 21(4):157- 161. Reiffel AJ, Kafka C, Hernandez KA, Popa S, Perez JL, Zhou S, et al.2. High-fidelity tissue engineering of patient-specific auricles for reconstruction of pediatric microtia and other auricular deformities. PLoS One. 2013; 8(2):e56506. doi: 10.1371/journal.pone.0056506. Levin M. The wisdom of the body: future techniques and approaches3. to morphogenetic fields in regenerative medicine, developmental biology and cancer. Regen Med. 2011; 6(6):667-673. doi: 10.2217/ rme.11.69. Zöller N, Valesky E, Butting M, Hofmann M, Kippenberger S,4. Bereiter Hahn J, et al. Clinical application of a tissue-cultured skin autograft: an alternative for the treatment of non-healing or slowly healing wounds? Dermatology. 2014; 229(3):190-198. doi: 10.1159/000362927. MorimotoN,ItoT,TakemotoS,KatakamiM,KandaN,TadaH,etal.An5. exploratory clinical study on the safety and efficacy of an autologous fibroblast-seeded artificial skin cultured with animal product-free medium in patients with diabetic foot ulcers. Int Wound J. 2014; 11(2):183-189. doi: 10.1111/j.1742-481X.2012.01064.x. Suzuki S, Morimoto N, Yamawaki S, Fujitaka J, Kawai K. A case of6. giant naevus followed up for 22 years after treatment with artificial dermis. J Plast Reconstr Aesthet Surg. 2013; 66(8):e229-233. doi: 10.1016/j.bjps.2013.03.018. Hayflick L. The limited in vitro lifetime of human diploid cell strains.7. Exp Cell Res. 1965; 37:614-636. Angel P, Hattori K, Smeal T, Karin M. The jun proto-oncogene is8. positively autoregulated by its product, Jun/AP-1. Cell. 1988; 55(5):875-885. Ryder K, Nathans D. Induction of protooncogene c-jun by serum9. growth factors. Proc Natl Acad Sci U S A. 1988; 85(22):8464-8467. Takahashi K, Sawasaki Y, Hata J, Mukai K, Goto T. Spontaneous10. transformation and immortalization of human endothelial cells. In Vitro Cell Dev Biol. 1990; 26(3 Pt 1):265-274. Schreiber M, Kolbus A, Piu F, Szabowski A, Möhle-Steinlein U, Tian J.11. Control of cell cycle progression by c-Jun is p53 dependent. Genes Dev. 1999; 13(5):607-619. Nordling CO. A new theory on cancer-inducing mechanism. Br J12. Cancer. 1953; 7(1):68- 72. Reddel RR. The role of senescence and immortalization in13. carcinogenesis. Carcinogenesis. 2000; 21(3):477-484. Border WA, Ruoslahti E. Transforming growth factor-beta in14. disease: the dark side of tissue repair. J Clin Invest. 1992; 90(1):1-7. doi: 10.1172/JCI115821. Minton K. Tumour immunology: TGF beta betrays immunity15. for tumorigenesis. Nat Rev Immunol. 2008; 8:89. doi:10.1038/ nri2263. Switzer WM, Salemi M, Qari SH, Jia H, Gray RR, Katzourakis A, et al.16. Ancient, independent evolution and distinct molecular features of the novel human T-lymphotropic virus type 4. Retrovirology. 2009; 6:9. doi: 10.1186/1742-4690-6-9. Larocque É, André-Arpin C, Borowiak M, Lemay G, Switzer WM,17. Duc Dodon M, et al. Human T-cell leukemia virus type 3 (HTLV-3) and HTLV-4 antisense-transcript-encoded proteins interact and transactivate Jun family-dependent transcription via their atypical bZIP motif. J Virol. 2014;88(16):8956-8970.doi: 10.1128/JVI.01094- 14. LeBreton M, Switzer WM, Djoko CF, Gillis A, Jia H, Sturgeon MM,18. et al. A gorilla reservoir for human T-lymphotropic virus type 4. Emerging Microbes & Infections. 2014; 3(1):e7. doi:10.1038/ emi.2014.7.