Everything you need to know about stem cells

1. What are stem cells?
2. Why are stem cells so unique?
3. How do stem cells remain unspecialised?
4. What are the different types of stem cells?
5. How are stem cells useful to us?
6. References

Each one of us, including you and I, start out our lives as a fertilized egg. This single cell divides thousands of times to eventually give rise to a fully functional human being with complex body parts that have designated functions, like the eyes, nose, limbs, fingers and toes. This gradual development from a single cell to multicellular life has been a topic of interest for many scientists - an eminent one among them being the German biologist Ernst Haeckel.

Ernst Haeckel, back in the 1800s, made an important observation. He noticed that the single celled fertilized egg, had the potential to give rise to all the cells of a multicellular organism. In awe of this cell’s unique capability, Haeckel decided to call it a ‘stem cell’, a term that centuries later would come to be a key player in the field of medicine and therapeutics (Ramalho-Santos and Willenbring, 2007).

What are stem cells?

After years of research, we now understand that stem cells are actually unspecialised cells which have the potential to give rise to the more specialised cell types in our body like the nerve cells and blood cells (Zakrzewski et al., 2019). They perform two important functions:

1. They help in embryogenesis: This is the process by which a fertilized egg develops into a functional embryo.
2. They help tissue regeneration: The cells in our tissues are constantly damaged due to internal and external stressors. Stem cells help replace these damaged cells, thereby maintaining the health of tissues. Different tissues have their own population of stem cells.

Why are stem cells so unique?

What sets stem cells apart from the other cells in our body? The answer is, their potency.

Stem cells, being unspecialised, have the unique ability to divide and differentiate into more specialised cell types. Unlike the specialised cells in our body which are confined to their cell fates, stem cells can give rise to varied cell types. For example, the mesenchymal stem cells (MSCs) present in tissues such as the umbilical cord and bone marrow have the ability to give rise to cells of the bone, muscle, skin and so on. However, the more specialised cells in the muscle tissue can only divide to make more muscle cells.

Additionally, stem cells can also self renew. Each time a stem cell divides, it gives rise to two types of cells. One cell is the more differentiated, specialised cell form, and the other is a copy of its unspecialised self. In other words, stem cells ensure that they maintain their own population within any tissue.

How do stem cells remain unspecialised?

Considering that most of the cells in our body perform very specialised roles, how do stem cells retain their unique unspecialised stem cell state? This is a question that continues to intrigue many scientists, and they believe it has something to do with how these cells are genetically programmed.

Moreover, studies also show that stem cells reside in their own little pockets within tissues. This is called the stem cell niche. It is the interaction of stem cells with their extracellular environment within this niche that also ensures that the unspecialised state is maintained (Mikkers and Frisén, 2005).

What are the different types of stem cells?

Based on their potency, stem cells can be classified as follows:

1. Totipotent stem cells: These are stem cells that can give rise to an entire organism. Example: Fertilized egg/zygote
2. Pluripotent stem cells: These are the cells present in a developing embryo and can give rise to the three basic layers of the body - the ectoderm, mesoderm and endoderm. They can therefore make all the organs of the body. However, unlike totipotent stem cells, they cannot make an entire organism on their own. Additionally, they cannot make the extraembryonic structures such as the umbilical cord and placenta. Example: Embryonic stem cells (ESCs) derived from the inner cell mass of preimplanted embryos.
3. Multipotent stem cells: These cells have lower potency when compared to both totipotent stem cells and pluripotent stem cells. They give rise to specific cell types only. Example: Hematopoietic stem cells (HSCs) present in the peripheral blood and bone marrow can give rise to the red blood cells (RBCs), white blood cells (WBCs) and platelets (Lee and Hong, 2019); Mesenchymal stem cells (MSCs) present in tissues such as the umbilical cord and bone marrow have the ability to give rise to several cells types including those of the bone, muscle, skin and nerves (Marion and Mao, 2006).
4. Oligopotent stem cells: These cells have further lower potency when compared to multipotent stem cells. Example: Myeloblast stem cells can give rise to certain types of WBCs, but not RBCs.
5. Unipotent stem cells: These cells have the lowest potency and can differentiate into only one cell type. Example: BFU-E (Erythroid burst forming units) are cells that can only differentiate to make RBCs (Dulmovits et al., 2017).
6. Induced pluripotent stem cells (iPSCs): These are lab-made cells, derived from adult body cells. These cells were first created by Kazutoshi Takahashi and Shinya Yamanaka, who introduced four proteins (Oct3/4, Sox2, c-Myc, and Klf4) into ordinary, unspecialised adult cells and reprogrammed them to resemble embryonic stem cells. They hence induced a state of pluripotency in normal, non-stem cells (Takahashi and Yamanaka, 2006).

How are stem cells useful to us?

Considering that stem cells have the unique ability to differentiate into different cell forms, they can be used to treat damaged tissues and organs. This field of medicine is called regenerative medicine. For example, hematopoietic stem cells (HSCs) are routinely used in the treatment of leukaemia. Leukaemia involves the uncontrolled division of blood cells. HSCs can therefore help replenish the stem cells in the bone marrow, which can in turn help produce healthy blood cells.

Additionally, stem cells are also being tested in clinical trials for the treatment of several other conditions (Hoang et al., 2022). Let us have a look at a few of them:

1. Liver diseases: Studies show that HSCs and MSCs have potential therapeutic effects in the treatment of liver diseases such as liver failure, cirrhosis and cancer.
2. Digestive disorders: Inflammatory bowel disease (IBD) involves chronic inflammation of the intestine. Treatment with HSCs and MSCs is shown to reduce inflammation and increase quality of life.
3. Arthritis: HSCs and MSCs have been shown to be effective in the treatment of osteoarthritis, specially when other treatment options fail.
4. Neurological diseases: MSCs have shown potential in the treatment of diseases such as multiple sclerosis, autism, stroke, Parkinson’s and Alzheimer’s.
5. Diabetes: Several clinical trials have shown MSCs to have considerable potential in the treatment of both type 1 and 2 diabetes.
6. Skin burns: MSCs have shown to be effective in the treatment of second and third degree burns.

With several clinical trials underway, we have indeed come a long way since Haeckel recognised the immense potential of a fertilized egg. In the years to come, with the rapid advancement in medical therapeutics, stem cell technology might come to be a key player in the treatment of several challenging diseases.

References

1. M. Ramalho-Santos and H. Willenbring, On the Origin of the Term “Stem Cell”. Cell Stem Cell. 1, 35-38 (2007). 10.1016/j.stem.2007.05.013. context
2. W. Zakrzewski et al., Stem cells: past, present, and future. Stem Cell Research & Therapy. 10, (2019). 10.1186/s13287-019-1165-5. context
3. H. Mikkers and J. Frisén, Deconstructing stemness. The EMBO Journal. 24, 2715-2719 (2005). 10.1038/sj.emboj.7600749. context
4. J. Lee and S. Hong, Hematopoietic Stem Cells and Their Roles in Tissue Regeneration. International Journal of Stem Cells. 13, 1-12 (2019). 10.15283/ijsc19127. context
5. N. Marion and J. Mao, Mesenchymal Stem Cells and Tissue Engineering. Methods in Enzymology. 339-361 (2006). 10.1016/s0076-6879(06)20016-8. context
6. B. Dulmovits et al., Characterization, regulation, and targeting of erythroid progenitors in normal and disordered human erythropoiesis. Current Opinion in Hematology. 24, 159-166 (2017). 10.1097/moh.0000000000000328. context
7. K. Takahashi and S. Yamanaka, Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors. Cell. 126, 663-676 (2006). 10.1016/j.cell.2006.07.024. context
8. D. Hoang et al., Stem cell-based therapy for human diseases. Signal Transduction and Targeted Therapy. 7, (2022). 10.1038/s41392-022-01134-4. context