Ethical issues in human organoid and gastruloid research

Munsie, Megan; Hyun, Insoo; Sugarman, Jeremy

doi:10.1242/dev.140111

Cited by 79 publications

(86 citation statements)

References 32 publications

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“…Organoids made out of human embryonic stem cells (hESCs) as well as so-called ‘gastruloids’ (table 1) relate to the fierce ethical debates on the use of embryos for research 33. Gastruloids are cultured out of human pluripotent stem cells (either hESCs or induced pluripotent stem cells (iPSCs)) and they closely recapitulate early stages of human development in a dish, including markers of primitive streak formation 33. This raises questions about the acceptability of ‘creating life in a dish’ and the extent of maturation of gastruloids that is allowed 33 35.…”

Section: Exchange Of Organoids: Questioning the Two Dichotomiesmentioning

confidence: 99%

Organoids as hybrids: ethical implications for the exchange of human tissues

2018

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Recent developments in biotechnology allow for the generation of increasingly complex products out of human tissues, for example, human stem cell lines, synthetic embryo-like structures and organoids. These developments are coupled with growing commercial interests. Although commercialisation can spark the scientific and clinical promises, profit-making out of human tissues is ethically contentious and known to raise public concern. The traditional bioethical frames of gift versus market are inapt to capture the resulting practical and ethical complexities. Therefore, we propose an alternative approach to identify, evaluate and deal with the ethical challenges that are raised by the increasing commercialisation of the exchange of sophisticated human tissue products. We use organoid technology, a cutting-edge stem cell technology that enables the cultivation of ‘mini-organs’ in a dish, as an example. First, we examine the moral value of organoids and recognise them as hybrids that relate to persons and their bodies as well as to technologies and markets in ambiguous ways. Second, we show that commercialisation of organoids is legitimised by a detachment of the instrumental and commercial value of organoids from their associations with persons and their bodies. This detachment is enacted in steps of disentanglement, among which consent and commodification. Third, we contend that far-reaching disentanglement is ethically challenging: (1) Societal interests could be put under pressure, because the rationale for commercialising organoid technology, that is, to stimulate biomedical innovation for the good of society, may not be fulfilled; (2) The interests of donors are made subordinate to those of third parties and the relational moral value of organoids may be insufficiently recognised. Fourth, we propose a ‘consent for governance’ model that contributes to responsible innovation and clinical translation in this exciting field.

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Section: Exchange Of Organoids: Questioning the Two Dichotomiesmentioning

confidence: 99%

Organoids as hybrids: ethical implications for the exchange of human tissues

2018

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“…The hiPSCs are suitable for many in vitro studies as indicated above with expanding use of organoids for regenerative medicine, drug screening and personalised medicine . However ethical concerns associated with the use of cultured human stem cells and organoids need to be considered . Autologous human cells are highly desirable for transplantation purposes, since use of the patient's own cells avoids the major in vivo problem of immune rejection (discussed further in Part B).…”

Section: Part A: Major Advances In Tissue Culture For Bioengineering:mentioning

confidence: 99%

“…30 However ethical concerns associated with the use of cultured human stem cells and organoids need to be considered. 31,32 Autologous human cells are highly desirable for transplantation purposes, since use of the patient's own cells avoids the major in vivo problem of immune rejection (discussed further in Part B). These are extraordinary advances that extend biomedical research towards clinical translation.…”

Section: Sources Of Human Stem Cells To Form Diverse Tissuesmentioning

confidence: 99%

“…The potential use of hiPSCs and organoids for clinical transplantation has increased exponentially, although concerns regarding safety and feasibility persist. 32 Some obstacles related to general feasibility of "stem cell therapies" are illustrated for skeletal muscle precursor cells (myoblasts or myogenic stem cells) classically considered to be derived from satellite cells that are quiescent reserve cells lying between the sarcolemma and basement membrane of adult myofibres, 84 week. 85 This may well account for the failure of most MTT clinical trials for DMD.…”

Section: Survival In Vivo and Other Obstacles To Successful Transplmentioning

confidence: 99%

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Obstacles and challenges for tissue engineering and regenerative medicine: Australian nuances

Grounds

2018

Clin Exp Pharma Physio

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The clinical need and historical approaches to tissue engineering as applied to regenerative medicine are introduced, along with comments on activities in this field around Australia, and then the huge advances for tissue culture studies are discussed (Part A). Combinations of human stem cells and new approaches for generating bioscaffolds present great opportunities for in vitro studies of basic biology and physiology, drug testing and high throughput screening for the pharmaceutical industry, and the advanced tissue engineering of organs and devices. The future here is bright. The major obstacles arise with in vivo application of these bioengineering advances using animal models and humans (Part B), and the complexity of living tissues and the challenges of increased scale required for clinical translation to the large human situation are first discussed. While clinical success seen with implantation of acellular bioscaffolds (with population by host cells) is likely to expand for human use, the major challenge relates to (generally) low survival in vivo of (donor or autologous) cells that are expanded and grown in tissue culture before implantation into the living body. Another major challenge is revascularisation of implanted tissues/organs at the human scale. The innovative approaches and rapid advances in tissue bioengineering hold great promise for overcoming these major obstacles and extending the clinical applications of these technologies.

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“…Hence, the issue opens with a thought-provoking piece (Huch et al, 2017) consisting of two parts: the hope of organoid research written by Huch and Knoblich, and the hype -including what it will take to overcome it -written by Lutolf and Martinez-Arias. Indeed, organoid culture is also not without some ethical challenges, as discussed in the Spotlight article from Munsie, Hyun and Sugarman (Munsie et al, 2017). The generation of human cerebral cortex in the dish, particularly coupled with genome editing, will require ethical consideration.…”

Section: What Can Organoids Tell Us About Morphogenesis?mentioning

confidence: 99%