Growing Organs, Stem Cells & Gene Therapy, Oh My!

Regenerative Medicine and its applications now, and in the future!

The potential for Regenerative Medicine to eliminate the organ donor list.

17 people die each day waiting for an organ transplant. Over 109, 000 people in the United States are on the National Transplant Waiting List as of September 2020. (Source)

What if doctors could create organs from patients' own cells and transplant them back into the patient’s body, eliminating the chance of rejection]. Well, with regenerative medicine, we can do just that.

What is Regenerative Medicine?

Regenerative Medicine(RM) is a field of medicine that is designed to replace or repair cells, tissues, or organs to establish or restore function. Regenerative Medicine has the potential to address a wide variety of medical diseases and conditions, that modern medicine cannot. RM therapies can restore or replace tissue that has been injured by trauma, damaged by disease, or harmed from wear and tear. It can also address chronic diseases such as neurodegenerative diseases and cardiovascular diseases, that are currently incurable with today’s medicine. RM is an expanding field with many different fields within it, such as stem cells, tissue engineering and gene therapy.

The Magical Cells In Your Body (a.k.a Stem Cells)

Chances are if you’ve heard of Regenerative Medicine, you’ve heard of stem cells. Stem cells are like children, that haven't grown up(differentiated) into what they want to be, like blood, skin, cardiac cells. Different types of stem cells can be found in the body: embryonic stem cells, adult stem cells, and induced pluripotent stem cells(iPSc).

Stem Cells can differentiate into all different types of cells in the body.

Embryonic Stem Cells

Embryonic stem cells(ESC) are stem cells derived from the cells in the human embryo. We can trace all cells in our body back to this little cluster of cells in the embryo. These stem cells are pluripotent, which means that they can differentiate into the three primary groups of cells in a human: ectoderm, endoderm, and mesoderm cells. This means that they can give rise to over 220 different cells in the body.

• Ectoderm Cells: forms the skin and nervous system
• Endoderm: forms the gastrointestinal, respiratory tracts, endocrine glands, liver and pancreas
• Mesoderm: Forms bone, cartilage, most of the circulatory system, muscles, connective tissue and more

ESC’s, like all stem cells, can self-renew and produce daughter cells of themselves. The reason why ESC’s are not widely used for research and medical usage is because of the ethical issues. To obtain embryonic stem cells, it involves killing an embryo from leftover embryos from the IVF process.

Adult Stem Cells

Adult stem cells are found in small quantities in adult tissues like bone marrow and fat. Adult stem cells, like every other type of stem cell, can make identical copies of themselves for an extended period of time and can differentiate into specialized cells. Adult stem cells are more limited than embryonic stem cells and can only give rise to various cells in the body. Unlike ESC’s, adult stem cells' main purpose is to maintain the steady-state functioning of a cell (homeostasis) and to replace dying cells, with some limitations, in our body.

Induced Pluripotent Stem Cells

Induced Pluripotent stem cells (iPSCs) are a type of pluripotent stem cells that are obtained by reprogramming human or animal differentiated cells. Like ESCs, iPSCs are pluripotent. iPSCs are called induced pluripotent, because they take specialized adult cells, such as a blood or skin cell, and genetically reprogramming it to an embryonic stem cell state. iPSCs are easier to obtain in large quantities than adult stem cells and face no ethical issues like embryonic stem cells. This is why iPSCs are most commonly used in stem cell research and applications.

How induced pluripotent stem cells are turned from a specialized somatic cell to a stem cell and then to a different specialized cell.

Tissue Engineering

When you think of Regenerative Medicine, you probably thinking of growing organs in a lab. Tissue engineering is a field in RM that aims to restore, maintain, or improve damaged tissues or whole organs.

A full trachea is made up of stem cells and scaffolding.

Tissue engineering can be used in not only regenerative medicine but also for testing drugs or consumer products. Tissue engineering can create tissues that mimic cells in the body so that scientists can test drugs and check reactivity without having to use humans. Tissue engineering has also been used to engineer skin tissue, bladders, small arteries, cartilage and even a full trachea. The future of tissue engineering could potentially bring 3D printing of entire complex organs, such as the heart, kidney and liver.

To successfully engineer tissue, four key components must be met.

1. Cells that will grow: Stem cells that are the building blocks for the engineered tissue. Like it was mentioned before, these pluripotent stem cells can give rise to many different types of cells, making it perfect to grow certain tissues.
2. A supporting environment for the cells: The stem cells can’t just sit on a petri dish and be expected to form into a 3D structure of a heart. A structure (scaffold) is needed to provide shape for the tissue construct. From the scaffold, the stem cells are seeded into the scaffold, and from there, the cells can begin to grow into a 3D structure.
3. Growth factors and Signaling: Growth factors are proteins that are employed to stimulate the stem cells to differentiate into a specific type of cell. It also tells the cells to divide and start growing.
4. Physical and Chemical Stimulation: pH levels, temperature, nutrients, 3D structure and other physical and chemical factors play a part in providing a good environment for cell growth and tissue maturation.

Tissue engineering has already become part of treatment in some cases, but we still have a long way to go before we are bioprinting hearts and livers, as they have so many functions and are very complex.

Gene Therapy

Gene therapy aims to introduce, remove, or change a cell’s genetic code to treat or cure a disease. Gene therapy can be used in disease treatment to introduce new base pairs/genes, remove base pairs/genes, or alter a target gene.

Using a virus, we can send the gene of choice into the body so it can interact with CRISPR-Cas9 and modify the genes in stem cells, to produce cells that have the corrected gene. This has the potential to treat or cure diseases.

This has implications in Regenerative Medicine because iPSCs are produced by introducing and expressing a specific set of genes, turning it into a stem cell. Another application in RM is the use of gene therapy in stem cells. Stem cells can be engineered to have an increased expression of repair proteins, improving the ability for it to regenerate tissue. Gene therapy relies on the use of a genetic transfer tool to edit the genes of interest.

CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats) is a gene-editing tool that can be used to cut and or replace DNA at a specific point of the genome. CRISPR is usually used as an immune response, using Cas9 to cut part of a virus's DNA, so next time that the body encounters this virus, it knows how to fight it. The two components of CRISPR-Cas9 is the guide RNA and the Cas9 enzyme.

• Guide RNA: Guide RNA can be used as a guide to finding a specific faulty gene where it can interact with the DNA, unwind it and perform a double-stranded break.
• Cas9: an enzyme that acts as a pair of molecular scissors and can cut the DNA at a specific location in the genome. The guide RNA can tell the Cas9 enzyme where to cut.

Gene therapy can be used in Regenerative Medicine to repair or replace faulty genes in regular genes or stem cells.

Key Takeaways

• Regenerative Medicine is an expanding field of medical research to repair or replace damaged tissues from age, trauma and diseases.
• Stem cells are undifferentiated cells, and pluripotent stem cells can give rise to over 220 different types of cells. Different types of stem cells include embryonic stem cells, adult stem cells and induced pluripotent stem cells.
• Tissue engineering aims to maintain, restore or improve damaged tissues or even entire organs. Tissue engineering can create arteries, bladders, bone, cartilage and potentially more complex organs such as the heart or liver.
• Gene therapy uses CRISPR-Cas9 to introduce, remove, or alter a cell’s genetic code to treat or cure diseases.

Regenerative Medicine has many applications in the field of medicine and can be used in tandem with traditional medicine to treat patients more effectively. RM has a very bright future ahead of itself, as scientists are looking into how we can cure genetic diseases with it, reverse neurodegenerative diseases and cardiovascular diseases and also play a part in human longevity in the ageing population.

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