Stem Cells

What Exactly Is Stem Cell Research?

There are cells in our body that have incredible power. They construct our bodies before we are born and repair tissues to keep is alive. For example, stem cells in the skin aid in wound healing, while stem cells deep within the bone marrow replace our blood and immune cells.

Stem cells are unique in two ways: they can replicate themselves (a process known as self-renewal) and they may grow into more specialized cells (a process known as differentiation).

Because of these characteristics, stem cells serve as living laboratories for medical research, allowing scientists to examine human biology in action from the earliest stages of development. They enable us to simulate the cellular underpinnings of disease and evaluate the efficacy of novel medications in the lab. The cells might potentially be used as live therapies to treat life-threatening disorders including cancer, diabetes, and Parkinson’s. The knowledge gained will aid in the acceleration of progress toward curing, preventing, o managing all diseases by the end of the century.

While stem cells have fascinated biomedical researchers for over a century, one Nobel Prize-winning discovery in the last two decades has accelerated the field: the ability to reprogram mature cells into stem cells in the lab.

The Discovery of Induced Pluripotent Stem Cells

While stem cells exist in all tissues of the adult body, those in the brain, muscle, and gut are not easily accessible for research. This changed in 2006, when Shinya Yamanaka and Kazutoshi Takahashi developed the first induced pluripotent stem cells (iPSCs).

How iPSCs are made

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Prior to this discovery, pluripotent stem cells were exclusively discovered in the embryonic stage. Unlike adult stem cells, which can only generate cells from their origin tissue, pluripotent stem cells may make nearly any cell in the body (hence the name: “pluri” means many, like plural). The four growth factors introduced are extremely active in early embryonic stem cells and, as they subsequently discovered, are critical to preserving the cells’ potential to differentiate into multiple kinds.

They essentially discovered a means to send mature cells — cells that were previously considered to be fated to become skin — back in time to a more potent, embryonic-like condition capable of producing any cell in the body. The finding ushered in a paradigm change in biology, allowing researchers for the first time to investigate any cell in the body independent of donor tissue availability. Shinya, who led the research team, was awarded the Nobel Prize in Physiology or Medicine in 2012 for discovering iPSCs only six years later.

Stem Cell Research Has Entered a New Era

iPSCs have fueled biological research over the last few decades. iPSCs may regenerate indefinitely under the correct laboratory circumstances, and scientists have perfected their production and transformation into several cell types. Researchers add growth factors or tiny compounds to a Petri dish to encourage them into generating specific cell types such as neurons, insulin-producing cells, or heart cells.

For example, given the correct inputs, iPSCs can develop into neurons with their own form, structure, and capacity to communicate with other cells via electrochemical messages. Cell development research aids in determining what those perfect signals are. Once researchers have a large number of new neurons, they can use them to study diseases and potentially develop new disease treatments. In fact, there is a huge push to employ iPSCs to answer the enigma of Alzheimer’s and other neurodegenerative illnesses. CZI contributed to the creation of an iPSC warehouse as part of this endeavor. Scientists may organize cells and examine the genetic alterations that cause Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), and other illnesses.

Some of these cell types are grown in a two-dimensional culture dish, similar to what you might see in biology class. Others are grown in three dimensions, generating multicellular clusters known as organoids that resemble sections of complex tissues such as the brain and kidney. For researchers researching the human brain or other human tissue, organoids are more realistic models.

Organoids: Stem Cells in 3D

Scientists employed iPSCs to build the first organoids, which are small three-dimensional groupings of cells, three years after they were discovered. These miniature models were a significant advancement in stem cell research because they are more representational of the three-dimensional structures that cells produce in the human body. Tissues include a variety of cell types that are structured in a certain way and link to work together. Researchers may explore some of the tissue properties found early in human development by observing cells develop and mature in an organoid.

Mini 3D models of human intestines, for example, give researchers a front-row seat to gut development, and lung organoids are assisting scientists in determining which cell types are infected by SARS-CoV-2 and how the immune response damages the lung.

Brain organoids are 3D representations of brain tissue developed in a dish. Some brain organoids resemble the developing cerebral cortex, the complex, multi-layered structure that forms the brain’s outer surface. Others are designed to resemble the spinal cord or the cerebellum, a fist-sized brain area at the rear of the head that regulates movement. Brain organoids provide researchers with an unprecedented chance to investigate living models of brain tissue.

In 2019, scientists sent roughly a hundred cortical organoids to the International Space Station to examine the impact of microgravity on human brain development.

Sergiu Pasca, a CZI grantee, and his colleagues claimed in 2021 that they had maintained brain organoids alive for over two years to explore how they evolve over time. They discovered that after 250-300 days, the cells undergo biochemical changes identical to those seen in newborn newborns’ developing brains. Pasca released research in 2022 demonstrating that transplanting organoids derived from human iPSCs into a rat brain might assist them mimic brain circuitry.

Stem Cell Research's Future

Breakthroughs in stem cell research have had a significant influence, yet much work remains in this field of study. iPSCs, for example, are not a perfect replica of stem cells created by nature. Scientists are attempting to determine why — and if the variations are significant in terms of research and therapy. Researchers are also trying to figure out how to reliably grow all of the different cell types in the human body, engineer cells to be immune-compatible, assemble cells into representative organoids, and massively scale up cell and organoids production.

Simultaneously, scientists are getting dangerously close to realizing the regenerative medicine dream — the ability to regenerate diseased and injured tissues and whole organs. While iPSCs make their way toward the clinic, these wondrous cells will continue to aid researchers in studying the human body in ways that were not previously possible. And they will continue to disclose the basic biology that creates and sustains humans.

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