Ethics in Health

S C I E N T I F I C C O N T R I B U T I O N

Is tissue engineering a new paradigm in medicine? Consequences for the ethical evaluation of tissue engineering research

Leen Trommelmans Æ Joseph Selling Æ Kris Dierickx

Published online: 24 July 2009

� Springer Science+Business Media B.V. 2009

Abstract Ex-vivo tissue engineering is a quickly devel-

oping medical technology aiming to regenerate tissue

through the introduction of an ex-vivo created tissue con-

struct instead of restoring the damaged tissue to some level

of functionality. Tissue engineering is considered by some

as a new medical paradigm. We analyse this claim and

identify tissue engineering’s fundamental characteristics,

focusing on the aim of the intervention and on the com-

plexity and continuity of the process. We inquire how these

features have an impact not only on the scientific research

itself but also on the ethical evaluation of this research. We

suggest that viewing tissue engineering as a new medical

paradigm allows us to develop a wider perspective for

successful investigation instead of focusing on isolated

steps of the tissue engineering process in an anecdotal way,

which may lead to an inadequate ethical evaluation. We

argue that the concept of tissue engineering as a paradigm

may benefit the way we address the ethical challenges

presented by tissue engineering.

Keywords Tissue engineering � Regenerative medicine � Ethics � Paradigm � Research

Introduction

Ex-vivo tissue engineering (TE) is a quickly developing

medical technology. It can be defined as

the creation of new tissue for the therapeutic recon-

struction of the human body, by the deliberate and

controlled stimulation of selected target cells, through

a systematic combination of molecular and mechan-

ical signals with the aid of extracellular scaffolds.

(Williams 2006a)

The in vitro combination of donated, substantially manip-

ulated and cultured human cells with supporting structures

and biomolecules yields metabolically active constructs:

human tissue engineered products (HTEPs). The constructs

are implanted, fostering and assisting the regeneration of

diseased or degenerated tissue in situ, thereby restoring a

particular function of the body. The HTEP can contain the

patient’s own cells, or it can be constructed from donated

cells. At present, all HTEPs are based on differentiated cells

(allogeneic keratinocytes for tissue engineered skin (Met-

calfe and Ferguson 2008) and autologous chondrocytes for

knee cartilage (Chung and Burdick 2008)), but adult and

embryonic stem cells are increasingly investigated as

possible cell sources (Kolf et al. 2007; Fernyhough et al.

2008; Passier and Mummery 2005; Kim and von Recum

2008, Bajada et al. 2008; Chim et al. 2008; Caplan 2007).

TE is considered to be a form of regenerative medicine.

Both TE and regenerative medicine suffer from a defini-

tional quagmire, and both terms are often used interchange-

ably in literature. However, in this article we will maintain

the distinction that regenerative medicine refers in the first

place to the aim of the intervention (to regenerate) and that

TE primarily refers to the method of the intervention:

creating an ex-vivo product and implanting it afterwards in

L. Trommelmans (&) � K. Dierickx Centre for Biomedical Ethics and Law, KU Leuven,

Kapucijnenvoer 35/3, Box 7001, 3000 Leuven, Belgium

e-mail: [email protected]

K. Dierickx

e-mail: [email protected]

J. Selling

Faculty of Theology, KU Leuven, Sint-Michielsstr 6,

3000 Leuven, Belgium

e-mail: [email protected]

123

Med Health Care and Philos (2009) 12:459–467

DOI 10.1007/s11019-009-9192-0

order to obtain regeneration. From this perspective TE is

part of the wider field of regenerative medicine.

Figure 1 gives an overview of the TE process in general.

Since the early 1990s (Langer and Vacanti 1993) the

field has advanced rapidly. While the proverbial ‘heart-in-

a-box’ (Ferber 1999; Lysaght et al. 2008; Moreno-Borchart

2004; Nerem 2000) may be a long way off—if ever

attainable—the development of smaller HTEPs for appli-

cations where medicine currently fails can be envisaged in

the medium term, and may in time have a profound impact

on the treatment of degenerative diseases, traumata and

congenital defects (Mirensky and Breuer 2008; Panetta

et al. 2008). The range of potential HTEPs is large: every

tissue prone to degeneration or that can suffer irreparable

damage is a candidate for TE. Tissue engineered skin

(MacNeil 2007; Pham et al. 2007) and autologous tissue

engineered cartilage implants for the knee (NICE 2005)

have been applied successfully, while other HTEPs such as

bone (Krampera et al. 2006), bladder and urinary tracts

(Atala et al. 2006; Korossis et al. 2006; Sievert et al. 2007),

heart valves (Mendelson and Schoen 2006; Migneco et al.

2008; Knight et al. 2008), heart muscle (Zimmermann et al.

2006), small-diameter arterial substitutes (Stegemann et al.

2007; Bordenave et al. 2008), vaginal tissue (Panici et al.

2007), intervertebral discs (Zhang et al. 2008; Williams

2007), vocal folds (Ford 2008), lymphatic tissue (Hitch-

cock and Niklason 2008), cornea (Shah et al. 2008), liver

(Fiegel et al. 2006, 2008), maxillo-facial applications (Zuk

2008; Moreau et al. 2007; Panetta et al. 2008) and other

applications are being developed.

Diseases due to tissue or organ degeneration are increas-

ingly common in ageing populations; therefore the thera-

peutic benefits of TE promise to be considerable (Grayson

et al. 2008; Rotter et al. 2007). The demand for HTEPs may

consequently increase significantly once they can be safely

produced at a larger scale, at an affordable price and if their

superiority to other therapies can be demonstrated.

The HTEPs that are available today for therapy are

relatively simple products, containing only a very limited

number of cell types, not interacting with the circulatory

system and not immunologically sensitive. They contain

cells that do not raise much ethical debate, are not used for

life-threatening conditions, and alternatives are available if

the HTEP is not efficient or must be removed. Yet even

these first HTEPs suffer from severe technical difficulties

such as the upscaling of the production of HTEPs and the

transfer of knowledge from one domain to the other, and

from economic and regulatory hurdles (Williams 2006b;

Bock et al. 2003).

As with other biomedical innovations, TE is under

ethical scrutiny (EGE 2004; Gordijn 2004; de Vries et al.

2008, Trommelmans et al. 2007). It has not yet received the

same attention as other advances in regenerative medicine

such as gene therapy and somatic cell therapy, or as

technologies like embryonic stem cell research or nano-

medicine. This may be in spite of—or maybe because of—

the many overlapping issues, and the seeming likeness of

TE with established interventions such as the use of med-

ical devices and transplants. However, we argue that TE

has characteristics that need to be considered carefully

when it is evaluated by ethicists, especially given the large

potential of TE and its possible impact on future health

care (Trommelmans et al. 2007).

A useful starting point for the ethical evaluation could

be to regard TE as a new medical paradigm, as is proposed

by tissue engineers themselves (Petit-Zeman 2001; Slavkin

and Bartold 2006). In this article we investigate if this

proposition may indeed be informative for the ethical

analysis of TE. We will therefore firstly evaluate this

contention as we find it in TE literature. We will then

present a more profound argumentation supporting this

argument. Thinking of TE in terms of a new paradigm may

allow us to more clearly see the features common to all

HTEPs that distinguish them from other interventions and

that may influence the ethical conduct of research and

therapy and subsequently develop appropriate approaches,

methods and standards for ethically responsible investiga-

tion and therapy.

Could TE be considered as a new medical paradigm?

According to T. Kuhn (1996)

the term ‘paradigm’ is used in two different senses.

On the one hand, it stands for the entire constellation

of beliefs, values, and techniques, and so on shared

by the members of a given community. On the other

hand, it denotes one sort of element in that

Cell manipulation

Therapy

Animal trial

Cell expansion

Combination with extracellular matrix and biomolecules

Exposure to stress

Packaging and transport/ control

Clinical trial

Human Tissue Engineered Product

Cell donor

Fig. 1 The tissue engineering process

460 L. Trommelmans et al.

123

constellation, the concrete puzzle-solution which,

employed as models or examples, can replace explicit

rules as a basis for the solutions of the remaining

puzzles of normal science. (p. 175)

Kuhn also refers to the reasons behind the development of

new paradigms: the inability of existing paradigms to

resolve specific problems, while he acknowledges the fact

that even in new paradigms existing knowledge is retained.

… the new candidate must seem to resolve some outstanding and generally recognised problem that

can be met in no other way. Second, the new para-

digm must promise to preserve a relatively large part

of the concrete problem-solving ability that has

accrued to science through its predecessors. (p. 169)

Starting from these definitions we investigated whether

the claim that TE is a new paradigm can be substantiated.

Keeping in mind that the terms TE and regenerative

medicine are often used interchangeably we undertook a

Pub-Med search which revealed 83 reviews containing the

combination (paradigm) AND (regenerative medicine) OR

(tissue engineering) in the abstract (search conducted

September 2008; all listed articles: 173). Of those 83, the

word paradigm was explicitly applied to TE and/or

regenerative medicine in 27 articles. We identified in these

articles the following arguments to label TE and/or

regenerative medicine as a new paradigm.

(1) The aim of the intervention is regeneration instead of

restoration and/or repair (Ford 2008; Moioli et al. 2007;

Kwan et al. 2008; Solchaga et al. 2001; Frank et al. 2004;

Scott et al. 2008; Gates et al. 2008; Hutmacher and Cool

2007; Tataria et al. 2006). (2) TE is an improvement to

existing treatments, including an answer to donor shortage

(Moioli et al. 2007; Scott et al. 2008; Behfar and Terzic

2007; Capi and Gepstein 2006). (3) TE is an innovative

process in which stem cells play an essential part (Kwan

et al. 2008; Scott et al. 2008; Gates et al. 2008; Huang et al.

2008; Bolland et al. 2007; Sales et al. 2005; Williams

2008). (4) It is a new paradigm because of the specific

construction of the HTEP and/or the multidisciplinarity of

the technology (Solchaga et al. 2001; Hutmacher and Cool

2007; Williams 2008; Butler et al. 2004, 2008; Gerecht-Nir

et al. 2006; Vunjak-Novakovic et al. 1999; Yang et al.

2006; Kretlow et al. 2007). (5) Successful TE depends on

the understanding and/or mimicking of biological pro-

cesses (Ford 2008; Frank et al. 2004; Tataria et al. 2006;

Williams 2008; Butler et al. 2004, 2008; Gerecht-Nir et al.

2006; Kretlow et al. 2007). (6) One type of HTEP (TE

skin) serves as a paradigm for other TE applications (Auger

et al. 2004; Simpson 2006; Simpson and Bowlin 2006;

Brouard and Barrandon 2003). Many articles combine

several arguments. Unfortunately, most of these articles do

not elaborate on their arguments, but restrict themselves to

a brief statement. This finding suggests that the terms

‘paradigm’ and ‘paradigm shift’ as they were first intro-

duced by T. Kuhn are sometimes used all too easily, giving

‘‘a slight whiff of self promotion to the author’’ (Marris

2008). Being part of a scientific and medical revolution and

creating a new conceptual framework certainly seems more

attractive than filling the gaps of a well known and tested

framework. Speaking of ‘a new paradigm’ with all its

revolutionary connotations where actually nothing truly

revolutionary is taking place, may be tempting for scien-

tists, especially in an environment where competition for

funding and media attention is fierce. Yet paradigms and

paradigm shifts are crucial concepts in science, and it is

therefore necessary to further substantiate this claim. For if

these claims are true, and TE is indeed a new paradigm, the

impact on our view of medicine, e.g. on its aim or on the

standard of care in medicine may change drastically. This

in turn may lead to a recalibration of what is required to

conduct research and medicine in an ethical way.

Both meanings of ‘paradigm’ can be identified in the

articles we analysed. Presenting TE skin as a model for

future TE applications (argument 6) is a clear example of

defining a paradigm as an exemplar. The argument that TE

is an improvement compared to other interventions is a

rather weak argument, as the idea of a paradigm shift

implies that it is not a continuation or improvement of an

existing approach, but on the contrary a new approach

toward a specific problem. It is therefore necessary to

examine the concept and method of TE, to identify its key

characteristics and to investigate how these key features

may influence the ethical evaluation of research ethics

issues in TE. Many retrieved articles do effectively refer to

the conceptual or methodological change that is occurring

through the development of TE, especially those that refer

to the regenerative aim of TE and those that describe TE as

a complex process, mimicking natural processes. As we

will argue further, there is indeed a conceptual and meth-

odological shift in TE research, justifying the idea of a

paradigm shift.

The concept and method of tissue engineering

To assess whether there is a conceptual and methodological

shift from ‘standard’ medicine to TE one has to examine

(1) the knowledge on which it builds, (2) its aim and (3) its

methods (Lysaght et al. 2008).

(1) TE draws on the increasing knowledge of biomateri-

als, the results from (stem) cell research and develop-

mental biology, and the increasing capacity to

intervene in cell development and cell differentiation

Is tissue engineering a new paradigm in medicine? 461

123

(U.S. Department of Health 2006). This quintessential

knowledge was not available until very recently.

Progress in regenerative medicine, including TE, and

stem cell research are strongly interconnected. To

paraphrase T. Dobzhansky’s famous statement: ‘noth-

ing in stem cell research makes sense except in the

light of regenerative medicine’ (Dobzhansky 1973).

(2) Unlike other interventions such as tissue transplants

and the use of prostheses, the goal of TE is explicitly

to coax the body through regeneration into its full

physiological capacity, curing hitherto incurable

diseases (Mummery 2004; Passier and Mummery

2003). Until recently medicine did not aim to

regenerate complex tissues and organs, because it

was considered impossible, due to the loss of

regenerative potential in the course of evolution.

Tissue damage initiates the formation of non-func-

tional, non-specific scar tissue, but does not normally

lead to regeneration in humans. Medicine therefore

makes the best of restoring the functionality of the

body through replacement (for example organ trans-

plants, artificial joint implants), enhancement (for

example braces) or mimicking a particular function of

the tissue or organ (for example the use of skin

dressings to prevent infection and dehydration).

(3) Within the field of regenerative medicine, which also

includes somatic cell therapy and gene therapy, TE

distinguishes itself by its unique method: creating a

complex, viable tissue in vitro and implanting it in the

patient (Williams 2006a). Unlike transplantation med-

icine in which unaltered organs are transferred from

donor to recipient, tissue engineers implant laboratory-

grown tailor-made constructs in the dynamic environ-

ment of the body. Regeneration made possible because

of scientific breakthroughs thus introduces a concep-

tual shift as well as the need for an entirely new set of

methods and approaches to realise this aim. So while

regenerative medicine in general, and TE in particular,

builds on existing knowledge and therapies, it aims to

overcome the known shortcomings of existing thera-

pies by applying specific methods.

One could argue that not TE as we have defined it, but

the more encompassing concept of regenerative medicine

is the new paradigm. Indeed, the concept and the actual

feasibility of regeneration as such is fundamentally dif-

ferent from what was previously the goal of medicine,

namely to restore function or at best to assist the sponta-

neously occurring regeneration of damaged tissues, but

never to deliberately induce regeneration. Yet, if we return

to Kuhn’s definition of a paradigm, it does not only concern

the fact that previously irresolvable problems may be

solved by the new approach, but also that this will be done

through a very specific method. Even compared with other

regenerative medicine approaches such as somatic cell

therapy or gene therapy, TE does have this specific meth-

odology. It is the only application that not only deliberately

induces regeneration, but also uses a complex ex-vivo

product, created by a wide array of techniques. Therefore

we would argue that TE in itself is a new paradigm.

To assess the ethical issues that are attached to this new

approach, it is however necessary to identify its key

characteristics and investigate if and how they may present

us with ethical issues.

Characteristics of the new paradigm

A paradigmatic approach may provide us with an

appropriate framework for the identification and evalua-

tion of the ethical concerns raised by TE research and its

applications. A key element of TE is that it presents a

hitherto unencountered complexity, due to the aim and the

method of TE, in which HTEPs combine properties of

medicinal products, medical devices, biologicals and

transplant surgery. Moreover, the process is continuous,

partly in vitro and partly in vivo. Although often

implicitly and sometimes explicitly acknowledged (Mikos

et al. 2006), this complexity and continuity are seldom

recognised as fundamental features that will deeply affect

the ethically responsible conduct of TE research and

therapy. One can isolate separate steps from the entire

process and treat them as if they were mere variants of

commonly known medical interventions and the ethical

issues they present.

However, the ultimate aim of TE is regeneration. This is

by definition a dynamic and continuous process. It is also a

complex process, which is currently not very well under-

stood. Therefore the starting point for the ethical analysis

of TE should be to explore the implications of these fea-

tures on how we understand and evaluate TE. This inves-

tigation will not only have to address the responsible

conduct of TE research. It may also include an investiga-

tion of conceptual issues underlying TE research, and more

broadly of regenerative medicine, such as the question

when regeneration is deemed ‘complete’. Considering TE

as a new medical paradigm therefore implies that the

continuity and complexity of the process are put at the

centre of the paradigm itself and of our understanding of it,

not as mere complementary characteristics that happen to

follow from the techniques that are developed by tissue

engineers. We will therefore focus in the following section

on these two features of TE and their consequences for a

responsible conduct of TE research and for the application

of HTEPs.

462 L. Trommelmans et al.

123

Complexity

The complexity of HTEPs is the result of three critical

features:

(1) Contrary to medicinal products, medical devices or

biologicals, HTEPs as products will always show

variability due to the presence of metabolically active

cells in the dynamic environment of the extracellular

scaffold (European Commission 2001). There is an

ongoing evolution within the HTEP itself: the cells and

the scaffold on which the cells are seeded interact with

each other. The scaffold, especially if it is combined

with growth factors or other bioactive molecules,

guides the migration of cells, their growth, differen-

tiation and death. The active cells on the other hand

produce extracellular material, and the matrix will

more often than not be biodegradable. Despite a well-

considered cell choice and the purification of the cells

used (European Commission 2001), scaffold architec-

ture, standardisation and upscaling in bioreactors

(Wendt et al. 2005) and the development and enforce-

ment of ‘Good Tissue Practices’, ‘Good Clinical

Practices’ and ‘Good Manufacturing Practices’ (Euro-

pean Parliament 2007; Farrugia 2006), individual

HTEPs will always show some variability. Deciding

on the amount of variability allowed within a HTEP or

even within a batch of HTEPs will have consequences

for the generalisability of trial results, for the product’s

safety and its price: stringent requirements will

inevitably lead to a restricted generalisability, a high

number of disqualified products, and a high price.

Lower standards may lead to inefficacious or even

unsafe products (European Parliament 2007).

(2) Implanted HTEPs initiate interactions between the

HTEP and the recipient’s body which also will vary

to some extent. These are not to be avoided, as in

prostheses or transplants, but to be encouraged

(Williams 2008). Understanding, assessing and guid-

ing these interactions during the entire process of

regeneration is crucial (European Parliament 2007).

Identifying the ideal implant time for the HTEP is but

one example. If the HTEP is too ‘green’ or too far

developed, it may not integrate with the surrounding

tissue (Caplan 2007). Understanding the interactions

between product and recipient during the regeneration

process is therefore of prime importance for the

successful development of TE. The dynamic and

living structure of the HTEP is after all its essential

quality. This consideration not only has scientific

importance, it also has ethical relevance. If there is a

mismatch between the dynamic generated in the

HTEP and the dynamic going on in the patient, the

product may at best be inefficacious, at worst unsafe

(Caplan 2007; Ahsan and Nerem 2005).

(3) The intervention is irreversible: once the process of

regeneration is initiated it is impossible to reverse it

completely. If it goes awry, the HTEP can at best be

removed. If the HTEP’s cells migrate or biomolecules

generate secondary effects at arbitrary sites, mere

reversion may be pointless. Back-up and containment

mechanisms have to be considered before the HTEP

is applied (EGE 2004). The interaction therefore,

although desired, has to be guided cautiously in order

to gain full incorporation of the product and to regain

and retain full functionality of the body, without

generating inflammation, unwanted cell growth,

rejection, or long term adverse events (European

Commission 2001). These three factors independently

contribute to the huge complexity of TE, but it is their

interaction and the accumulation of complex chal-

lenges that each of them presents, many of them

moreover difficult to qualify or quantify, that present

us with unencountered challenges.

The limited value of pre-trial research and non-human

animal trials adds another level to the complexity of these

issues. These pre-clinical tests normally provide informa-

tion concerning safety and efficacy issues. The predictive

value of animal models for TE is however poor due to their

unsuitability to fully mimic the complexity of the human

environment during regeneration. We have as yet no gen-

eral standards or models for animal trials with HTEPs

(Nadal-Ginard et al. 2006; Tawqeer et al. 2004; Giannoni

et al. 2005). The heterogeneity of HTEPs, the variability of

the regenerative process and the lack of animal models

make it difficult to proceed from pre-clinical research to

animal trials and subsequently to clinical trials the same

way as in other biomedical research. Using healthy vol-

unteers to test HTEPs is problematic, as it would be

completely unethical to remove healthy tissue from persons

and replace it with a HTEP which, however cleverly

designed, can only mimic healthy tissue.

Continuity: tissue engineering as a chain of events

The continuity of the TE process contributes to the com-

plexity of HTEPs. This process starts as early as the cell

choice for the HTEP and the choice of biomaterials and ends

when the HTEP is fully incorporated in the recipient’s body,

without causing negative secondary effects. It is started in

vitro, but completed in vivo. Patient eligibility (Ingber and

Levin 2007), cell choice, the construction of scaffolds

(Stocum 1998; Hollister 2005), the in vivo growth of the

HTEP, the design and culture conditions in the bioreactor

(Wendt et al. 2005), the surgeon’s skills (Lilford et al. 2004),

Is tissue engineering a new paradigm in medicine? 463

123

the interaction between the HTEP and the recipient’s tissues

and post-operative behaviour of the HTEP recipient

(Campbell et al. 2001) all play a decisive role in the final

success or failure of the HTEP. This implies that we need to

consider every stage of the TE process with the entire process

in mind. The effect of events or interventions early in the

production of the HTEP such as cell donor characteristics

may become apparent only late in the development or

application of the HTEP. This is not only relevant from a

technical point of view, but also from other perspectives:

designing HTEPs that show excellent promise in the labo-

ratory but cannot be realistically produced on an appropriate

scale, that cannot be safely implanted or that may be rejected

by patients on moral grounds are examples of ways not to go,

both for economic and ethical reasons.

Impact of the TE paradigm on the ethical analysis

The ultimate goal, the complexity and continuity of the

process are core features of the TE paradigm. Although

these features are implicitly acknowledged, we argue that

they should be the explicit starting point for the evaluation

of the ethical issues in TE research and therapy because

they may enlighten the evaluation of every aspect of TE:

the management of the entire process from product design

to follow-up and therapy, their efficacy and safety, the risks

involved, the amount of data that investigators need before

proceeding to clinical trials and therapy and their reliability

and relevance. It may also have an impact on the informed

consent procedure in trials and therapy (Trommelmans

et al. 2008a, b).

TE may not present new ethical issues as such, but well

known challenges are taken to a higher level compared to

research with medicinal products or medical devices.

Acknowledging the inherent complexity of HTEPs and the

continuity of the TE process as distinctive features com-

mon to all TE interventions will assist ethicists in assessing

well known challenges such as determining the products’

safety, guiding informed consent processes etc. in this very

new setting of TE. The variability of the products and of

the interactions between product and patient increases the

amount of uncertainties inherent to the TE process. Inter-

preting pre-clinical results (Ginis et al. 2003), trial results

and adverse events during and after trial will be more

difficult as the number of uncertainties increases. The

design and conduct of clinical trials, their risks, benefits

and anticipated added value will have to be argued con-

vincingly given the difficulties resulting from the com-

plexity of the TE process on the one hand and the presence

of other reliable technologies on the other hand.

Due to the continuity of the process, trials alone will

furthermore not suffice to make comprehensive projections

about the future safety, efficacy and quality of the therapy;

or to fully appreciate long-term changes in quality of life

(NICE 2005). TE as a continuous process necessitates

follow-up of post-trial events (Wood et al. 2006) at least

for as long as the interaction between HTEP and recipient

continues, as secondary outcomes of the HTEP’s intro-

duction will not necessarily be detected during a trial. To

evaluate long-term performance, in trials and in therapy,

the establishment of comprehensive registries of trials and

therapies could be a crucial step (Williams 2006c). The

systematic review of the impact of various elements and

interactions in the TE process and products, gathered from

different trials and therapeutic applications, may provide us

with clues that single trials cannot reveal but which may

well lead to a considerable improvement of the application

of HTEPs.

Given the huge costs of setting up a trial, it is clear that

the demarcation of the end point of a trial does not only

involve scientific and therapeutic issues, but financial

considerations as well. However, the safety of the trial

participant should get priority over all other issues.

Therefore the end point of the trial and the design of post-

trial follow-up schemes need to be determined and argued

carefully, in order to minimise the risks for the trial par-

ticipant and to gather as much relevant information for

future therapy as possible. Another argument for extensive

follow-up is that new knowledge may come to light after

the end-point of the trial that is relevant for the selection of

the cell donor, for the entire TE process and for the pro-

spective patient.

Ethics committees that are involved in the assessment of

clinical trial protocols will have to take these issues into

consideration.

Conclusion

TE has not yet caught the public imagination, neither has it

received the same attention from the ethics community as

other advances in regenerative medicine, such as gene

therapy, or as other new technologies such as nanomedi-

cine, which may be used for TE purposes but are not dis-

tinguishing features of it. Moreover, according to some,

there are no specific ethical issues related to TE provided

one does not use human embryonic stem cells for HTEPs

and the donation of cells for TE is free, without payment,

and the donor is adequately informed (European Parlia-

ment 2007). This disqualification of the need for an ethical

analysis of TE may be based on the idea that at face value

there are no ethical issues in TE that are not already treated

elsewhere. Another reason for this lack of interest is that

actual applications of TE so far are limited. TE neverthe-

less deserves specific ethical attention, given its large

potential to treat a very broad range of degenerative

464 L. Trommelmans et al.

123

diseases, traumata and congenital defects. This analysis has

not yet been systematically started. The ethical questions

raised by the development of TE may be investigated from

different angles, such as the socio-economic impact of TE,

anthropological issues and research ethics issues. We have

restricted ourselves in this contribution to the latter.

We have argued that the aims and methods of TE are

distinct from other medical approaches, enticing us to

consider TE as a new paradigm whose key features are its

complexity and continuity. It is this complexity and con-

tinuity that are inherent to the TE paradigm that require an

appropriate evaluation. No single step of the TE process

can be isolated from the entire web of events. We have as

yet very little or no experience in dealing with products and

processes that are so complex and that have a previously

unattained and unattainable aim: regeneration. Therefore

the ethical investigation of TE needs to cover more than the

analysis of isolated steps of the TE process or of isolated

components of the HTEP to create efficacious and safe

HTEPs, as previously unknown problems may emerge,

exactly because of the complexity and continuity of TE.

The main challenge for the ethical assessment of TE is

therefore not primarily to address issues such as the min-

imisation of risks on a case-by-case basis, but to analyse in

depth how the concept and features of TE influence the

way we address these issues.

We have argued that considering TE as a new paradigm

may provide us with a wider perspective for successful

investigation. TE’s success will not depend exclusively on

our ability to solve fundamental scientific questions but

also on our ability to translate accepted ethical require-

ments for research, trials and therapy into the reality of the

complex undertaking that TE is.

Acknowledgements The research for this contribution was sup- ported by the STEPS-project, funded by the European Commission,

FP6-50046.

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