BioRevolution #10 - Organoids

Before diving into more discussions on organoids, I realized that it’s crucial to first address the concept of organoids itself. Recently, while talking about Organoid Intelligence, a member of the audience asked, "What exactly is an organoid?" This question illuminated the need to clarify this concept for everyone, not just those within the scientific community. As someone deeply motivated to make science accessible beyond the realm of scientists, it felt strange to have overlooked such a fundamental point.

My BSc. graduation thesis was almost entirely related to this topic, and I began with a similar introduction… In a world where everything has become so personalized, where social media platforms use advanced personalization, it was inevitable that healthcare would also move away from a one-size-fits-all approach. In an environment where personal outcomes are expected, the processes themselves must also be tailored to the individual. So, when we think of personalized treatment and its associated processes, what comes to mind? Naturally, the answer is organoids, the very subject of our discussion. By creating organoids from a patient's own cell sources, a unique, patient-specific treatment process is designed. This truly represents a revolutionary shift in the field of healthcare.

Today, we’re delving into the topic of organoids. This won’t be our first or last conversation about organoids, so I encourage you to read carefully and take in this fascinating subject.

Scientific Perspective

An organoid is essentially a laboratory-grown, three-dimensional, miniaturized version of an organ. These structures are derived from stem cells or differentiated cells and possess the ability to self-organize and renew themselves. Organoids contain multiple cell types found in an organ and mimic some of the key features of real organs, such as their cell composition and basic functions. Typically, they arise through the spontaneous self-organization of their constituent cells, although in certain cases, specific hormonal or growth factor signals are introduced to direct the differentiation of very immature stem cells. [...] Organoids serve as simplified, tissue-engineered in vitro models that can replicate the complex structure and function of tissues. They are developed in three dimensions, meaning they have a more realistic structure compared to traditional flat cell cultures.

Creating an organoid involves a fascinating process that starts with sourcing the right cells, which can be stem cells like embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), or even somatic stem cells. These cells are remarkable because they have the potential to become various types of specialized cells found in our organs. To initiate organoid formation, scientists first obtain these cells through a process of mechanical or enzymatic dissociation, where tissues from organs or previously preserved organoids are carefully broken down into smaller fragments or individual cells. [...]

Once the cells are isolated, they are placed in a special culture medium that encourages them to group together, forming small 3D clusters known as spheroids. These spheroids are the building blocks of organoids and can be created using different methods, including suspension cultures, bioreactors, or even roller bottles. After spheroid formation, they are transferred into a gel-like substance, such as extracellular matrix (ECM) or matrigel, which provides a supportive environment that mimics the natural surroundings of cells in the body. The choice of medium and the specific growth factors added to it are tailored to the type of organoid being created, whether it's for the stomach, liver, or even a tumor model. Over time, with careful nurturing, these spheroids develop into fully grown organoids that closely resemble their in vivo counterparts, offering a powerful tool for research into human biology and disease. This entire process can take several weeks to months. [...]

Organoids are powerful tools used in scientific research to better understand human biology and disease. They serve as miniature models of real organs, allowing researchers to study how organs develop, function, and respond to various treatments in a controlled laboratory environment. Because organoids can mimic the complexity of human tissues, they are especially valuable for studying diseases, testing new drugs, and even exploring personalized medicine approaches, where treatments can be tailored to the specific needs of individual patients. Additionally, organoids offer a promising alternative to animal testing, providing more accurate human-relevant data while reducing the need for animal models in research.

??Video Suggestion

Organoids Animation by XVIVO | Scientific Animation

Market Perspective

The organoids market is set to experience a remarkable expansion, with projections indicating growth from USD 88 million in 2021 to USD 290.8 million by 2028, achieving a Compound Annual Growth Rate (CAGR) of 18.4% during the 2022-2028 period. This growth underscores the rising demand and integration of organoids across various sectors, including biopharmaceutical companies, contract research organizations, and academic and research institutes.

-Industry Research Biz’s Organoids Market Growth Insights 2023-2030 Report-

Startup Ecosystem:

1. OrganoTherapeutics

Luxembourg based company

Founded in 2019

OrganoTherapeutics focused on accelerating the development of treatments for neurodegenerative diseases, with a particular emphasis on Parkinson's disease. The team has created innovative patient-specific models, including organoids and assembloids, which replicate Parkinson’s pathology more accurately than traditional models. These IP-protected models have been instrumental in collaborative projects with academic and industry partners across Europe, the USA, and Japan over the past four years.

*Their latest funding round was a Seed round, which concluded on July 26, 2023. Notably, they are backed by three investors: KHAN Technology Transfer Fund I , Creative Destruction Lab (CDL), and others.

2. HUB Organoids

Nederland based company

Founded in 2013

HUB Organoids is a leader in patient-derived organoid technology, offering a cutting-edge platform that bridges the gap between laboratory research and clinical application. Their patented technology, based on the discovery of Lgr5+ stem cells, allows for the creation of organoids that retain the genetic and epigenetic characteristics of the original tissue, including disease-specific mutations. HUB's extensive biobank includes thousands of patient-derived organoids across various tissues and diseases, providing drug developers with robust, patient-relevant models for drug discovery and clinical trials. This approach enhances the accuracy and success rates of therapeutic developments.

*HUB Organoids B.V. awarded 弗若斯特沙利文公司 ’s 2024 Technology Innovation Leadership Award for transforming drug development with highly advanced organoid technology.

3. Parallel Bio

Cambridge based company

Founded in 2021

Parallel Bio is at the forefront of advancing immunotherapy by combining cutting-edge human immune organoids with large-scale bioengineering and computational methods. Their platform enables the discovery of new drugs with unprecedented accuracy, allowing for the rapid identification of therapies that are effective from the outset. Unlike traditional models, Parallel Bio's technology can predict how a drug will perform across an entire population, leading to the development of therapies that are safe and effective for a broader range of patients. This approach represents a significant leap forward in personalized medicine and the future of drug discovery.

*Parallel Bio secures $4.3M in seed funding, led by Refactor Capital, with other investors including Breakout Ventures ; Jeff Dean , SVP of Google AI; Y Combinator ; several biotech-focused funds; and senior executives at global pharmaceutical companies.

4. Rosebud Biosciences

San Francisco based company

Founded in 2020

Rosebud Biosciences is an early-stage startup focused on developing therapies for rare genetic diseases in children. By using micropatterned organoids derived from human induced pluripotent stem cells (hiPSCs) with specific gene mutations, Rosebud models human development to screen for potential cures. Their "2.5D" organoids, which contain multiple cell lineages, offer significant advantages over traditional disease modeling methods. This innovative approach allows for efficient screening of various therapies, including small molecules, RNA therapies, and gene editing technologies like CRISPR.

*Rosebud Biosciences has successfully secured funding through multiple rounds, including a $275K grant, $500K from an accelerator/incubator, and early-stage venture capital, with support from investors like Y Combinator , National Science Foundation (NSF) , 10X Capital , Arvantis Group , and Gaingels .

??Groundbreaking News

FDA Modernization Act 2.0: transitioning beyond animal models with human cells, organoids, and AI/ML-based approaches

The FDA Modernization Act 2.0 represents a significant shift in drug development by removing the mandatory requirement for animal testing, opening the door for alternative methods such as organoid technology. Historically, animal models have been the cornerstone of drug testing, but they come with high costs, ethical concerns, and issues with translating results to human trials.

As the industry moves towards patient-derived organoids, these models offer a more accurate and scalable alternative for drug screening, preserving the genetic makeup of the original tissue and allowing for better prediction of drug efficacy and toxicity. The growing adoption of organoids, particularly in areas like immuno-oncology and inflammatory diseases, signals the dawn of a new era in patient-centric drug development, making the FDA's recent legislative changes a pivotal moment in modern medicine.

Future Perspective

I will present to you two scenarios, two imaginative journeys into the future perspective.

• Let's fast forward to a time when organoids are readily available and imagine how your experience as a patient might unfold.

You walk into the doctor’s office and describe your symptoms—symptoms that you’ve never experienced before. The doctor reviews your digital twin, a virtual model of your body that tracks your health in real-time. However, this particular symptom originates from a part of your body that isn’t monitored by a biosensor, and there’s no record of past issues in this area. Imaging techniques are employed, and a tumor is detected. Your doctor updates your digital twin with this new information, and the process of gathering a sample begins.

A biopsy is taken from the tumor, and organoid research is initiated. Scientists create a miniaturized version of your tumor—an organoid—that mimics its behavior. Through this organoid, disease modeling is conducted, and the resulting data is integrated into your digital twin. This allows your digital twin to reflect the progression of the disease accurately. Multiple treatment scenarios are then tested, and the five most promising drugs are identified. Next, these drugs are tested on the organoid, and the most effective one is selected for your treatment. Meanwhile, a biosensor tailored to your condition is installed, enabling comprehensive, real-time monitoring of the disease.

As you discuss these developments with your doctor, your digital twin offers insights into potential future illnesses, providing preventive healthcare recommendations. The biggest question lingering in your mind, however, is, "How could this disease have been prevented?"

Even in a world equipped with advanced technology that makes us feel secure, people of that time will be pondering new challenges. "How was this not prevented?" We are always on the frontier of the most advanced systems, yet we still find ourselves questioning and striving for something more.

• Imagine a future where the concept of organoids has advanced to the point where we can create entire organs from scratch. Now, let's delve into a thought experiment: If we were to construct all the organs of a person using organoids, would that be considered cloning?

You step into the lab, where scientists have successfully grown a complete set of human organs from organoids. The organs are perfectly functional, each one crafted to replicate the exact characteristics of a real human body. But here's the intriguing question: If we assembled these organs into a full body, would this creation be a clone?

The next step in this scenario is even more mind-bending—could this body, made entirely from organoids, actually be brought to life? The notion of animating a body grown from organoids leads to a cascade of questions about identity and existence. Would this being, this organoid "clone," begin its existence with the knowledge and experiences that you possess, or would it start from a blank slate, learning and growing just like any other human being?

Now, consider your feelings towards this creation. Would you feel a sense of envy toward this being, made to mirror your physical form, yet unburdened by your past? The idea of an organoid clone living a life parallel to yours, with the potential to carve out its own unique path, raises profound questions about self-identity and the nature of life itself.

As we ponder these possibilities, it's clear that even in a world of incredible technological advancements, we would continue to wrestle with the implications of what it means to create life, to replicate our own existence, and to confront the emotions that arise from such groundbreaking developments. Would you embrace this new form of life, or would you find yourself questioning its place in the world—and your own?

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