The 9th Annual San Antonio Conference on Stem Cell Research & Regenerative Medicine (or RegenMed SA, as it’s commonly known) will convene at the BioBridge Global Campus on February 9-10, 2023. RegenMed SA promotes collaboration among people and organizations interested in stem cell research, tissue engineering and regenerative medicine.
Following the keynote speech on Friday, February 10, the conference will feature a lunchtime panel on organoids, moderated by Jenny Hsieh, Director of the UTSA Brain Health Consortium. StemBioSys CTO Travis Block is one of a number of experts scheduled to participate on the panel.
What are Organoids?
Organoids are 3-D self-assembled systems that contain a diversity of cell types from a given tissue and mimic a particular organ in the body. They are created when pluripotent stem cells are allowed to form a sphere in culture and then differentiated as such. This process mimics elements of fetal development, in which cells share spatial cues with each other; when they differentiate, they are able to self-organize into a multicellular organ system. These differentiated “mini-organs” have overlap with what groups refer to as spheroids and assembloids. Often the use of these terms leads to semantic confusion in the literature.
The Organoid Hype Cycle
The thought process surrounding use of organoids in stem cell research adheres quite closely to the Hype Cycle, a graphical representation developed by Gartner to depict the various stages of technology adoption. Organoids experienced a considerable ramp-up of excitement and expectation within the field from 2014 to 2019. This phase of hype was so pronounced that, during the 2019 International Society for Stem Cell Research (ISSCR) Conference, Block joked to colleagues that the meeting had ceased to be about stem cells and was now primarily an “organoid conference”.
Following this peak of expectation, however, there has been a dramatic pullback with regard to the hype surrounding organoids in recent years. Block estimates that only 10% of the 2022 ISSCR conference (and perhaps even less) was devoted to organoid system discussions.
A rendering of Gartner’s Hype Cycle. Block believes that the concept of organoids is currently in the Trough of Disillusionment phase of the cycle. Image credit: Jeremy Kemp
What has caused such a marked loss of interest? Block offers several compelling reasons.
Mass production and uniformity are issues. In the early phase of the hype cycle, scientists created beautiful fluorescent images of organoids; they demonstrated gene expression that suggested that the cells within these organoids were maturing to a greater extent than in other models - and that those cells remained viable much longer than in traditional mono-cultures. Unfortunately, reliable techniques for mass production of organoids don’t currently exist. While scientists were able to successfully mimic organoids, assaying them in experiments proved (and continues to prove) challenging. The process of growing a large quantity of organoids is extraordinarily time consuming, and it’s very difficult to ensure that large groups of organoids are at the exact same stage of development at the same time.
Nutrient diffusion and cell health in organoids is difficult to quantify or guarantee. As organoids are bathed in nutrients and grow in size during an assay, the nutrients are not always able to diffuse to the cells at the center of the sphere; this leads, in many cases, to a necrotic core. Compounding this issue is the fact that it is difficult to know if organoids contain necrotic cores until after they have been assayed. Crucially, while cell life and death is binary, cell health leaves a lot of room for variability.
Organoid development can be a “no-man’s land of complexity.” In the field of bioengineering, successful model system design balances biologic relevance with ease of use. Organoids are intensely biologically relevant, but at this point they are not easy to assay and can take many months to grow - which precludes their use in high-throughput drug screening or process development. This is why, in order to strike a better balance between relevance and ease of use, the scientists at StemBioSys focus their efforts on the extracellular matrix, a significant component of physiology that is often neglected in organoid models.
The Future of Organoids
According to Block, the use of organoids in cell research is currently in the Trough of Disillusionment phase of the Gartner Hype Cycle. That’s not to say, however, that organoids don’t still hold substantial promise - simply that the expectations surrounding them have been tempered somewhat. Moving forward, organoids will likely be used in a complementary manner to systems that are perhaps less biologically relevant but simpler and easier to scale. In addition, various companies are developing tools for more consistent organoid development; one day in the future, they might even replace animal models. Ultimately, given their high degree of variability, only time will tell how much of a lasting impact organoids will make in the field of cell regeneration.
Located in San Antonio, TX, StemBioSys develops cell culture technologies licensed from The University of Texas Health Science Center, San Antonio. Our work represents the next evolution in stem cell research. For more information about StemBioSys and our patented technology, please contact us.