Harnessing the Benefits of AI for Cell Reprogramming

?Human cell, tissue, or organ transplantation saves many lives and restores vital functions when no other options are available.

Transplantation has become a successful worldwide practice in the last 50 years. However, there are significant differences between countries in terms of access to suitable transplantation as well as the level of safety, quality, and efficacy of human cells, tissue, and organ donation and transplantation.

Considering all the awareness campaigns and protocol updates, there′s still a huge unmet need in this field. As a matter of fact, do you know that 104,234 patients are on the national transplant list and that 17 people die each day waiting for an organ transplant? Being the kidney the most needed.

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According to organdonor.gov 42000+ transplants were performed in 2022

?Organ transplantation is critically dependent on identifying potential organ donors and converting them into actual donors. The former is a significant challenge that relies heavily on medical team training, an inefficient approach given the rarity of deceased organ donation, particularly in small centers. According to multiple retrospective cohort studies, between 30 and 60% of potential organ donors are either not identified or are not referred to an Organ Donation Organization (ODO), or the organ cannot be delivered due to crystalization.

Several solutions were proposed to solve these issues, AI donor-patient matching using AI on HER information, Organ banking via?cryopreservation, 3D bioprinting using organ-like scaffolds, and a nascent field of AI for cell reprogramming and transplant.

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Cryopreservation:

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The ability to cryopreserve living biological systems, such as cells, tissues, organs, and even whole organisms, began in 1949 with the preservation of fowl sperm using glycerol, a cryoprotective agent (CPA) that protected the sperm cells during freezing1. This was followed by significant proof-of-concept cryopreservation of mammalian blood and embryos using other CPAs. These and other studies also showed that ice crystallization during freezing limited success, particularly in larger systems. Efforts to overcome this barrier resulted in "vitrification," a method of avoiding crystallization by using higher concentrations of CPAs and faster cooling rates.

Zonghu Han et al. created "nanowarming," which accomplishes both goals at the same time by generating heat from within and throughout the organ rather than just at its surface. Iron oxide nanoparticles (IONPs) and CPA solutions are perfused throughout the organ vasculature during nanowarming. The organ is vitrified and then rewarmed on demand by placing it in a radiofrequency (RF) coil, which generates alternating magnetic fields from the electric current flowing through it.

As a result, they were able to cryopreserve rat kidneys for up to 100 days and rewarm them on demand. Recovery of organ function was demonstrated in vitro by normothermic machine perfusion and in vivo by removing both native kidneys at the time of transplant in a rat transplant model. Following nanowarming and transplantation, full renal function was restored, with the transplanted organs sustaining the recipient animals' lives.

Mammalian embryo cryopreservation became a reality and transformed the field of reproductive technology by avoiding crystallization during both cooling and rewarming. However, due to the inability of conventional convective rewarming (i.e., surface warming) to provide rapid and uniform heating rates across these larger scales, preventing crystallization during rewarming in larger bulk systems, such as whole kidneys, remains elusive. Indeed, vitrification followed by long-term kidney (or other organs) transplant success has never been replicated.

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3D Bioprinting

This method prints layer upon layer of tissue that will not be rejected by the recipient using "bio-ink," a printable material made from the patient's own cells. However, one critical challenge in progressing from tissue to complex organ has been how to get the blood flowing to keep the cells alive, and researchers have devised several approaches to this. Threading tiny channels through the organ, where blood vessels develop when implanted in animals, or seeding channels with endothelial cells, which line the inside of blood vessels, are two examples.?

Materials for 3D bioprinting of tissues and organs perform a variety of functions, including protecting, supporting, and maintaining cell activity, promoting cellular proliferation and differentiation, guiding tissue regeneration, and promoting functional maturity. Because human tissues and organs are extremely complex, both structurally and functionally, traditional materials or any single component material cannot have all of the characteristics required to reconstruct tissue functions. The creation of new materials that support high precision and rapid prototyping, have specific biological functions and are more compatible with printers and printing software has become an unavoidable trend.

Because bioprinting falls under the regulatory domain of "regenerative medicine, medical devices, and biologic drugs," regulators must apply existing rules to this uncertain field. As of now, it is unclear whether policymakers will be able to effectively regulate bioprinting using existing regulations, or if a new, specialized regulatory process will be required.

Policymakers must consider a wide range of concerns when deciding how to regulate 3D organ printing (3DP). Because the technology is still in its early stages, there is a great deal of uncertainty about the actual risks and ethical concerns. One ethical concern is that 3DP organs may only be available to wealthy people, while less wealthy people will be denied access to these organs.

Another issue to consider is safety. Because 3DP may necessitate stem-cell technology and the patient's own cells may be used for replication, assessing the safety risks is difficult. Because stem-cell therapy cannot be tested on a large number of healthy people, effective clinical analysis is limited. Furthermore, 3DP biotechnology may open up new applications beyond 3DP organs, such as human capacity enhancement for military use. Developers could use the technology to make military officers or even terrorists less vulnerable to injury in battle, but this would create a whole new set of problems for law enforcement and national security.

Which are the biggest players on the field?

?3DP is a huge green field and many companies are trying to develop new technologies, from bio-ink up to printers to get a potential market share for the future business. Just to name a few are: ?

1)?????Organovo, the company behind the world’s first 3D printable liver tissue, Not only are they currently bringing revenues in by providing pharmaceutical companies with their aa3exVive3D? Liver Tissue for drug toxicity testing, but they have partnered with major companies in the health space including L’Oréal and Merck, and are planning on introducing their exVive3D? Kidney Tissue.

2)?????CELLiNK was the first company to release the first universal bioink in 2016 and has played a crucial role in turning 3D bioprinting into a multi-billion dollar industry.

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Now, we′ve all heard about AI in many many fields of life science and our daily lifes but, what about using it for cell reprogramming?

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The use of artificial intelligence in cell reprogramming

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Cell reprogramming is a technique that allows scientists to transform one type of cell into another, such as skin cells into neurons or blood cells. This technique holds enormous promise in regenerative medicine, drug discovery, and personalized therapies. Cell reprogramming, on the other hand, is extremely difficult because it necessitates precise control of gene expression and epigenetic changes that occur during the transition.

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One application of AI in cell reprogramming is determining the best combination of factors to induce the desired cell fate. Deep learning, a type of AI that can learn from large amounts of data, has been used by researchers to discover new reprogramming recipes for various cell types such as cardiomyocytes, hepatocytes, and astrocytes. Deep learning can also assist in determining the best timing and dosage of the factors, as well as the best culture conditions for the reprogrammed cells. Wayne R. Danter of 123Genetix was among the first to create an unsupervised deep learning algorithm for producing aiPSC.

?Another use of AI in cell reprogramming is to monitor and evaluate the process's quality and efficiency. Researchers, for example, used machine learning, a type of AI that can learn from examples and patterns, to create algorithms that can classify reprogrammed cells based on their gene expression profiles or morphology. Machine learning can also aid in the detection and elimination of unwanted or abnormal cells that may emerge during the reprogramming process.

?AI in cell reprogramming is still a nascent field, but it has already shown promising results and opened new avenues for research. By combining the power of AI with the potential of cell reprogramming, we can imagine a day when there′s no need to look for a new donor, we could just reprogram autologous cells and print an organ in an office next to the operating rooms and transplant it. Think about the logistics issues we might be able to solve and how many lives could be saved.

Now, is there a market big enough to support the investment in these new technologies?

The market for organ transplants is expected to increase up to USD 15 - 22 billion by 2028 according to several sources and the main drivers are the increased increase in the incidence of acute diseases and chronic diseases, which in turn results in an increase in the number of organ failures. For instance, diabetes and high blood pressure are the most common causes of end-stage renal disease, where kidney transplants or dialysis are the only treatment options to keep a patient alive.?Another big driver is the fact that we are living longer, and the geriatric?population is more prone to organ malfunction, especially the liver, heart, and kidney, thus, in turn, driving the growth of the market.

As you might have seen, there are different and complementary angles trying to solve the organ transplant problem. As with all in science, it takes time, knowledge, and investment so, are you an investor working in the field? or a startup trying to solve this puzzle? Leave a comment below.

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