Has the secret to lab grown organs been within us this whole time?🧫🫀
104,000 people are currently on the transplant list and that’s just in the US. Let me say that again, 104,000 people! But it doesn’t end there, out of those, 17 people die each day and a new name is added to the transplant list every 9 minutes.
The demand for these organs always outweighs the supply hence the long waiting lists. And what’s worse is that the levels of organ failure increase day by day due to various reasons like chronic disease, traumatic injury or loss of blood supply.
But are we just going to sit around and hope that someone gets kind enough to give away a part of themselves at the cost of their own wellbeing, or are we going to take advantage of the way technology is evolving day by day.
Luke Masella was a young boy that lived with a congenital bladder condition that impaired his bladder function and quality of life. But, in 1999, Dr. Atala and his team created a replacement bladder for Luke using his own cells, grown on a biodegradable scaffold in the laboratory.
This was a great accomplishment in the history of regenerative medicine and we could potentially be looking at one day able to receive other organs made from our own cells like kidneys, liver or even the heart. Either by growing them in the lab using scaffolds or even 3D printing using a hydrogel that contains those specific cells.
What’s the secret sauce though?🤔
The magic all lies in stem cells. They are undifferentiated cells that have the potential to transform into various cell types in the body. Their ability to complete their telomeres (which basically means maintain chromosomal stability and prevent chromosomal degradation) allows them to divide for a longer time compared to normal cells.
Stem cells can be found throughout the body, especially in the bone marrow where they divide to make new blood cells. They have also been traced in the brain, skin, muscle, liver, heart and blood. They basically lie dormant in these areas until there is need to regenerate lost or damaged tissues.
The different kinds of stem cells🔬
As much as stems cells are undifferentiated, they can be categorized into 5 major types according to the kind of cells they are able to transform into, but for now we’ll focus on the first three;
Totipotent stem cells: These are the most powerful out of all the 5 since they can develop into a fully functioning living organism. Kind of like baking a cake but instead of flour, sugar, milk and eggs, you have the totipotent stem cells. Embryonic cells within the first few days of cell division are the only cells that are totipotent. They can give rise to tissues that make up the embryo as it develops from zygote to a multicellular organism, called embryonic tissues, and tissues that bring about the structures that aid in the development of the embryo like the placenta or umbilical cord, called extraembryonic tissues. Basically, these cells can form ALL tissues of the body. Yap, I meant all.
Pluripotent stem cells: Now after fertilization, the zygote undergoes cell division multiple times forming a hollow ball of cells called the blastula. The blastula folds inward forming a structure called the gastrula and this process creates three germ layers, you better not be thinking about dirt. Anyway, the pluripotent stem cells have the capability to differentiate into any of these layers which are:
The ectoderm that is the innermost layer and gives rise to the skin and the nervous system, the mesoderm that deals in the development of several cell types such as bone, muscle, and connective tissue and lastly, the endoderm layer which becomes the linings of the digestive and respiratory system, and form organs like the liver and pancreas. For lab grown organs, these cells are our best friends.
Let’s not get it twisted
Pluripotent and totipotent cells tend to get confused quite a lot since they both the ability to divide into specialized cells but don’t worry the difference is profound. Totipotent stem cells basically have the ability to differentiate into all cell types and consequently, a whole organism but for the pluripotent stem cells, as much as they can develop into most cell types, they don’t have the ability to form the extraembryonic tissues therefore, they can’t develop into an entire organism on their own. Got that? Ok let’s keep going.
Multipotent stem cells : These can only differentiate into cell types within one particular lineage. For example, neural stem cells (that can differentiate into neurons and glial cells), mesenchymal stem cells (important for formation of muscle, bone and cartilage) or hematopoietic stem cells (generate all types of blood cells).
Lab grown organs you say?
Ok now that we’re done with all that sciency stuff let’s try and understand how a tiny cell can become a whole organ and you know what that means, more sciency stuff😉
Remember how we said pluripotent stem cells were our best friends, ya, let’s breakdown the whole process step by step to understand how it all goes down in vivo.
The process🧪
In the early stages of embryo formation, pluripotent stem cells undergo linear specification where they basically commit to forming one of the three germ layers which will determine the type of tissues and organs the cell will give rise to. Signaling molecules are then secreted by the cells within and around the developing tissue playing a very vital role. The concentration and timing of the secretion determines the response action. For example, high concentrations of BMP signaling can induce cells to become part of the ectoderm while others like morphogens establish concentration gradients across developing tissues. Cells differentiate into specific cell types based off of the level of concentration. The signaling molecules also affect cell division, boundary formation, migration of cells and survival.
Once the signaling molecules are released, the cells begin to differentiate into precursor cells that further transform into organ-specific progenitor cells which are relatively multipotent.
As much as the cells are able to divide, they also need to find ways to get into the right organization and this process is called pattern formation. It mainly relies on the action of signaling molecules but is also under genetic control. Take into account, homeobox genes, they play a critical role in specifying the positional identity of cells along the anterior-posterior axis in organisms.
Following this, the cells begin to divide, migrate and differentiate to form the functional components of the organ. This could be blood vessels needed to supply the organ with nutrients and oxygen, valves in the case of the heart and even synaptic connections in the nervous system.
As development progresses, the cells within the organs mature and acquire their specialized functions. The fully developed organs begin to interact with other body organs and tissues to maintain internal stability and perform its functions. Of course, we can’t forget that the adult stem cells continuously contribute to tissue renewal and regeneration as time goes on.
So what’s the plan?
Now if you’re like me you’re probably wondering, ‘well if the stem cells repair and maintain the organ tissues why is organ failure still causing death?’ This could be because of a number of reasons like poor formation of blood vessels, immunological rejection or even disease projection but that’s a bedtime story for another time. For now, let’s discuss the elephant in the room, how are we combatting this issue?
We saw earlier that the demand for organs greatly surpasses their availability and it was between 1950 and 1960 that scientists started exploring the possibility of creating artificial organs and tissues. Cells, which could be pluripotent, multipotent, primary or even specialized, were to be isolated from the patient. From there they were cultured and expanded through provision of necessary nutrients and conditions for growth. Once they have differentiated into specialized cells, they are seeded onto a scaffold that provides structural growth and guides tissue growth. Scientists have tried to grow organs in the lab using this approach but, they were only able to create organoids which are tiny three-dimensional cell cultures that mimic the structure and function of real organs to a certain extent.
Yap…. that’s a human bladder and liver in our reach. Unfortunately, they aren’t 100% ready to be transplanted into humans. But why is this?
Come on now let’s go full scale
So, they were able to replicate the structure and cells of the organs, great, but what about the function. Think about the liver, it needs to be able to filter blood and regulate electrolytes, to replicate these processes would require complex technology.
Another issue is vascularization; organs require a network of blood vessels to provide oxygen and nutrients to the cells within the organ. Ensuring proper vascularization in lab-grown organs has been a major hurdle. Without an adequate blood supply, the organ cannot survive or function effectively.
The production of lab grown organs is a tedious process that tends to be time consuming and expensive. Finding ways to make it more cost effective and scalable is another ongoing challenge especially due to the scarcity of expertise.
Just like any other scientific discovery, safety and efficacy tests must be done to evaluate the functionality in living organisms. But the good news is, in 2013, scientists at the University of Edinburgh successfully transplanted lab-grown kidney organoids into mice. These organoids partially mimicked the structure and function of a human kidney and were able to filter blood and produce urine when transplanted into the mice, so, we are clearly on the right path.
But is anyone paying attention to these blocks? And how do we plan on dealing with them?
Many institutes and companies are devoting their time and resources to find that one day there will be a quick and effective solution to organ failure. Like Organovo that’s leveraging the 3D bioprinting technology to create not only the complete organs as an alternative but also intricate vascular networks within lab grown organs or, Harvard’s Wyss Institute that’s pioneering the development of organ-on-a-chip systems, which are microfluidic devices that mimic the functions of organs. Even though they are not fully developed, they are definitely promising.
Generally, I believe that the future of medicine lies within regenerative medicine. Just think about all the possibilities, organ and tissue engineering, 3D bioprinting, gene editing, artificial intelligence, immunotherapy, the list goes on and on. Individually these technologies are great, but imagine what we could accomplish if we combined them?
