Commercialization of Organoids

doi:10.1016/j.molmed.2019.12.002

Trends in Molecular Medicine

Volume 26, Issue 3, March 2020, Pages 245-249

https://doi.org/10.1016/j.molmed.2019.12.002 Get rights and content

Organoids have been successfully exploited for drug screening, disease modeling, pathogenesis, and regenerative medicine. Herein, we discuss the progress achieved in the commercialization of organoids in the last few years. We further elaborate on the concept of organoid biobank and highlight ethical and regulatory issues surrounding organoid research and commercialization.

Section snippets

Organoid Research

Animal models are the gold standard in vivo models for research and drug discovery. However, the majority of drugs that clear preclinical animal trials fail in the clinical stage due to incompatibility issues between animals and humans. Organoid technology could better mimic human physiology compared with animal models [1, 2, 3]. Drugs that were found to be efficacious in animal models did not work in organoids (such as PTC-124, Ataluren). Thereby, predicting failure of these drugs was later

Commercializing Organoids

The demand for commercial organoids will increase in the coming years [12], with at least 19 companies interested in organoid business (Figure 1A). It is 2019 where organoid commercialization has taken center stage, with the incorporation of six companies. Of these, Organome and HUB (Hubrecht Organoid Technology, a not-for-profit organization) are dedicated to organoid biobanking, while the rest are focused on manufacturing, commercialization of organoids, or other organoid-related

Capital Funding and Resources

The current companies are mostly operating via three models: (i) venture/private funding, where the companies get the funding usually in return for certain equity; (ii) close partnerships between the companies, carving out a win–win scenario; or (iii) direct collaboration with research institutes or clinicians. Sometimes more than one model is employed. Figure 1C,D depicts the total funding received by the companies over the years as well per company, respectively.

Living Organoid Biobank

Organoid Biobank (Figure 2) is a platform established by HUB and was the brainchild of Professor Hans Clevers. HUB aspires to be a central reservoir for a collection of organoids derived from both healthy individuals and patients from around the world. It is to be noted that there is a need to get a license to work with organoids using the Clevers methods in the commercial domain. Currently, companies such as Epistem, Cellesce, Crown Biosciences, and STEMCELL Technologies have licensed the

Ethical and Regulatory Challenges

The usage of animal models is always plagued with ethical questions [14]. Organoid research still involves some ethical and regulatory challenges, which has somewhat restricted the work on them. Since organoids are derived primarily from stem cells, the ethical issues surrounding stem cell research and stem cell therapies encompasses organoids as well [14]. Usage of animal-derived ECM ‘matrigel’ in organoid production [14] is flagged as an ethical concern because of its compatibility issues

Concluding Remarks

Organoid technology, though still in its formative years, is potentially revolutionary as it could someday act as a bridge between preclinical and clinical trials to ensure better drug testing models or more personalized precision medicine. At present, organoid production is confined to laboratory-scale with only a few companies aiming towards scalable manufacturing. The primary intended customers of these organoid-development companies are researchers and pharmaceutical companies. Some

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Engineering stem cell organoids
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Organoid center strategies for accelerating clinical translation
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There are more references available in the full text version of this article.

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There is a growing interest in the development of technologies to probe and direct in vitro cellular function for fundamental organoid and stem cell biology, functional tissue and metabolic engineering, and biotherapeutic formulation. Recapitulating many critical aspects of the native cellular niche, hydrogel biomaterials have proved to be a defining platform technology in this space, catapulting biological investigation from traditional two-dimensional (2D) culture into the 3D world. Seeking to better emulate the dynamic heterogeneity characteristic of all living tissues, global efforts over the last several years have centered on upgrading hydrogel design from relatively simple and static architectures into stimuli-responsive and spatiotemporally evolvable niches. Toward this end, advances from traditionally disparate fields, including bioorthogonal click chemistry, chemoenzymatic synthesis, and DNA nanotechnology, have been co-opted and integrated to construct 4D-tunable systems that undergo preprogrammed functional changes in response to user-defined inputs. In this review, we highlight how advances in synthetic, semisynthetic, and bio-based chemistries have played a critical role in the triggered creation and customization of next-generation hydrogel biomaterials. We also chart how these advances stand to energize the translational pipeline of hydrogels from bench to market and close with an outlook on outstanding opportunities and challenges that lay ahead.
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MPS models have paved the way for organ-on-a-chip drug testing. Current research focuses on the commercialization of organ-on-a-chip models via start-ups [76,211,268], and on the identified difficulties and downfalls of MPS models, and ways to resolve them. Currently, the proof-of-concept for most organ-on-a-chip models is tested on cell lines or animal-derived culture.
The low probability of a drug candidate's clinical success, the time consumed and the high cost of bringing a drug from concept to market emphasizes the need for new approaches to drug discovery. Recent innovations in microfluidic technologies, including organ-on-a-chip, droplet microfluidics and high-throughput screening are revealing the potential of these platforms to address some of these challenges, due to the small volume of samples consumed, short processing time, and improved process control. Here, we review selected recent progress in the development and application of microfluidic technologies in drug screening and drug delivery, highlighting the trends and associated challenges.
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Such biobanks are reducing the requirement for geographic proximity of clinical research institutions to organoid/stem cell–derived tissue research laboratories. Through these biobanks/biorepositories the correct ethical regulations are carefully defined and maintained.78,79 Organoid lines are very appealing models to study intercellular crosstalk in health and disease, and can be compared with respective data from stratified patient cohorts.27,28,40
Homeostatic functions of a living tissue, such as the gastrointestinal tract, rely on highly sophisticated and finely tuned cell-to-cell interactions. These crosstalks evolve and continuously are refined as the tissue develops and give rise to specialized cells performing general and tissue-specific functions. To study these systems, stem cell–based in vitro models, often called organoids, and non–stem cell–based primary cell aggregates (called spheroids) appeared just over a decade ago. These models still are evolving and gaining complexity, making them the state-of-the-art models for studying cellular crosstalk in the gastrointestinal tract, and to investigate digestive pathologies, such as inflammatory bowel disease, colorectal cancer, and liver diseases. However, the use of organoid- or spheroid-based models to recapitulate in vitro the highly complex structure of in vivo tissue remains challenging, and mainly restricted to expert developmental cell biologists. Here, we condense the founding knowledge and key literature information that scientists adopting the organoid technology for the first time need to consider when using these models for novel biological questions. We also include information that current organoid/spheroid users could use to add to increase the complexity to their existing models. We highlight the current and prospective evolution of these models through bridging stem cell biology with biomaterial and scaffold engineering research areas. Linking these complementary fields will increase the in vitro mimicry of in vivo tissue, and potentially lead to more successful translational biomedical applications. Deepening our understanding of the nature and dynamic fine-tuning of intercellular crosstalks will enable identifying novel signaling targets for new or repurposed therapeutics used in many multifactorial diseases.
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Further, depending on how organoids are used in translational research (e.g., identifying personalized treatments, transplantation, biobanking), ethical issues concerning safety, privacy, and consent will inevitably arise (Boers, et al., 2016). In addition, particular potential clinical applications necessitate specific considerations, such as the ethical acceptability of enrolling children in clinical trials involving organoids (Schneemann, et al., 2020) and the commercialization of organoid technologies (Choudhury et al., 2020). With some exceptions, early conceptual scholarship about these issues has focused predominately on gastruloids, brain organoids, and intestinal organoids (Boers and Bredenoord, 2018; Boers, et al., 2019; Hyun, 2017).
Organoid research is enhancing understanding of human development and diseases as well as aiding in medication development and selection, raising hopes for even more future therapeutic options. Nevertheless, this work raises important ethical issues and there is a paucity of data regarding patients' perspectives on them. We report on 60 interviews with adult patients or parents of pediatric patients from diverse disease populations who receive medical care at a major academic research institution in the United States. Interviewees expressed broad support for organoid development and use. However, patients viewed brain organoids, and sometimes gonadal organoids, as morally distinct; and some organoid research poses moral concerns. Nonetheless, patients generally understood the potential value of such research and approved of it, provided it was aimed at good intent and conducted with ethical oversight and a robust consent process. These data should help inform conceptual and policy deliberations about appropriate organoid use.
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Trends in Molecular Medicine

Section snippets

Organoid Research

Commercializing Organoids

Capital Funding and Resources

Living Organoid Biobank

Ethical and Regulatory Challenges

Concluding Remarks

References (15)

Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients

Cell Stem Cell

Engineering stem cell organoids

Cell Stem Cell

Organoid center strategies for accelerating clinical translation

Cell Stem Cell

Digitalized human organoid for wireless phenotyping

iScience

A functional CFTR assay using primary cystic fibrosis intestinal organoids

Nat. Med.

Organogenesis in a dish: modeling development and disease using organoid technologies

Science

Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche

Nature

Cited by (24)

Chemical and biological engineering strategies to make and modify next-generation hydrogel biomaterials

Microfluidic trends in drug screening and drug delivery

Everything You Always Wanted to Know About Organoid-Based Models (and Never Dared to Ask)

Patients' perspectives on the derivation and use of organoids

Organoids and organs-on-chips: Insights into human gut-microbe interactions

Engineering of tissue constructs using coaxial bioprinting

Trends in Molecular Medicine

Science & SocietyCommercialization of Organoids

Section snippets

Organoid Research

Commercializing Organoids

Capital Funding and Resources

Living Organoid Biobank

Ethical and Regulatory Challenges

Concluding Remarks

Cell Stem Cell

Cell Stem Cell

Cell Stem Cell

iScience

A functional CFTR assay using primary cystic fibrosis intestinal organoids

Nat. Med.

Organogenesis in a dish: modeling development and disease using organoid technologies

Science

Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche

Nature

Science & Society
Commercialization of Organoids