Introduction

Considering an adult human body, scientists have proposed that it is composed of about 200 different cell types, each with its specific function. Among this diversity, the most important ones are the stem cells. A general concept about them is that these are the parent cells that give rise to all other cell types. In the following words, we will have a look into their definition, location in the human body, importance, functions, their differentiation into other cell types, their role in the fields of biotechnology and genetic engineering for the prevention as well as treatment of various genetic defects and congenital anomalies. We will have an overview of ongoing research topics and future horizons about stem cells and their biomedical importance.

What are Stem cells?

These are the cells that do not belong to any specific, committed or differentiated and functionally active cell type. Rather, they have the potential to differentiate into any specific cell type which is functionally active. They are also capable of self-renewal, the most important property of these cells. They may occasionally be dividing, i.e., in muscles etc., moderately dividing, i.e., in germinal epithelium, or rapidly dividing cells, i.e., in the epithelium of the gastrointestinal tract, depending upon their location in the body and the organ system to which they belong.

Cell Differentiation Process

Before going into details, let us have the concept of cell differentiation. Cell differentiation is a signal-guided process by which a cell is destined to be a part of a certain tissue. Virtually all the cells of the body have the same genetic material, but we see that most of the body cells are specialized for a specific function. This specific functionality is achieved through the cell differentiation process in which certain genes of a cell are inactivated (turned off) and certain genes are allowed for gene expression. This results in different sets of proteins formed by the cells. For example, an eye lens cell has the same genetic makeup as that of a glandular cell of the stomach, but they have different sets of activated genes which results in their different functionality.

Classification of Stem Cells

According to the potency, stem cells may be totipotent, pluripotent, multipotent, oligopotent, and unipotent cells.

• Totipotent stem cells are the actual stem cells. They are completely undifferentiated and can differentiate into any specific cell type. Any totipotent stem cell is capable of forming a complete viable offspring if suitable conditions are provided. The best example of totipotent stem cells is the zygote and the cells formed after first and sometimes after the second cleavage. These are not present in an adult. They are also known as embryonic stem cells.
• Pluripotent stem cells are slightly differentiated cells. They can give rise to nearly all the cell types but are not able to form a complete viable offspring if isolated and grown independently. For example, cells of the morula stage of the embryo.
• Multipotent stem cells are somewhat more differentiated cells. They can give rise only to cells of closely related families. Fibroblasts present in adult connective tissue are classic examples of this type.
• Oligopotent stem cells are more differentiated than the multipotent stem cells. These cells can give rise to different cells of a cellular family. The best known of these are myeloid or lymphoid stem cells that can differentiate into different types of white blood cells (WBCs or leukocytes).
• Unipotent stem cells are the most differentiated cells. They can give rise to only a particular cell type to which they belong, but they have the ability of self-renewal, which fully differentiated cells do not have. This is the most abundant stem cell type found in an adult human body. The multipotent, oligopotent and unipotent stem cells are also known as adult stem cells.

Functions of the Stem Cells

Functions of the stem cells include:

• Maintenance of a reserve of self-renewing cell population
• Renewal of a specific cell type after normal wear and tear or any physical or psychic trauma
• Provision of a continuous supply line of new cells in epithelial areas where cells are continually sloughed off.

Specific stem cell types in an adult human with their location and specific functions

Bone marrow

Bone marrow contains a specific portion of cells called pluripotent hematopoietic stem cells. These cells are capable of forming all different blood cell types. When these cells divide, some of the daughter cells remain undifferentiated pluripotent cells, maintaining the pool of reserve stem cells and others differentiate into multipotent cells. These multipotent cells differentiate into different colony-forming unit-lymphocytes. Some of CFUs are colony-forming unit-granulocytes, some are colony-forming unit-erythrocytes, -monocytes and megakaryocytes etc. Each CFU is a unipotent stem cell capable of giving rise to a specific type of completely differentiated, mature and functionally active cell.

Skin

Skin is composed of two layers. A superficial layer is known as the epidermis and a deep layer is called the dermis. The Epidermal part of skin consists of stratified squamous keratinized epithelium in which epithelial cells are arranged into five layers or strata (sing. stratum). The basal layer or stratum Basale (also known as stratum germinativum) consists of principal skin epithelial cells called keratinocytes. These keratinocytes are actually unipotent stem cells that can give rise to only their own clones. As the skin is subjected to continuous wear and tear, these keratinocytes divide continuously to maintain normal skin thickness and texture. The newly formed cells are continuously moved outward towards the skin’s external surface. Under a microscope, these cells show a specific character by exhibiting numerous mitotic figures, i.e., active centrosomes, mitotic fibres, etc.

Gastrointestinal tract

Along the length of the whole alimentary canal or gastrointestinal tract, surface epithelium changes according to need. Different parts of GIT have regional variations in the type of epithelium, but one all these epithelia share a single character that the cells present in the basal layers of these epithelia are mostly unipotent or sometimes oligopotent stem cells. Like the skin, the alimentary canal is also subjected to continuous wear and tear, these basal cells continually divide and replace the older cells. Two types of these stem cells are described in detail below.

Epithelium of the tongue contains many specialized taste-sensing cells called taste buds. Near these taste buds, close to the basal lamina of epithelium, small basal cells are present. These cells represent the stem cells for taste buds. They are oligopotent and can differentiate into sustentacular cells (supporting cells) and taste cells to regenerate them.

Lamina propria of the stomach in its fundus and body contains different types of gastric glands. One of these glands is the fundic gland that secretes acid and most of the digestive enzymes. The epithelium of these glands contains undifferentiated multipotent stem cells along with other cell types. These stem cells are columnar and located in the neck of the fundic gland. They are responsible for the continual production of different specialized cells of the gland as well as gastric pit and overall gastric luminal surface.

Olfactory epithelium

The olfactory epithelium is of pseudostratified columnar variety which basically contains three types of cells. 1) Olfactory cells 2) Sustentacular cells 3) Basal cells. Out of these three types, basal cells represent the reserve cells or stem cells. The other two varieties have short life spans, so they are continuously replaced by these basal cells. Unlike the keratinocytes of the skin, these basal cells are not unipotent rather than multipotent stem cells that can differentiate either into olfactory cells or sustentacular cells. These are small, spherical cells that lie in a single layer in the basal part of the epithelium.

Liver

The liver is a specialized organ that has got a remarkable self-regenerative capability. After a partial hepatectomy (surgical removal of a part of the liver), even when 70 to 80% of the total liver mass is sectioned, the liver can gain its previous weight and size within a few weeks. This regeneration is only possible if liver cells known as hepatocytes have at least unipotent stem cell character. These are very special stem cells that normally remain dormant (in the sense that they are non-dividing) but can be activated when needed. After a trauma to the liver, such as hepatectomy, cirrhosis or any accidental tissue damage, these cells enter into the cell cycle and divide into new hepatocytes. This division continues until the liver gains its original mass.

Capillaries

Some poorly differentiated cells are located along the length of continuous types of capillaries with elongated cytoplasmic processes that surround these capillaries. These cells are called pericytes. Pericytes are basically contractile cells as they contain contractile apparatus, i.e., actin, myosin, and other contractile proteins. Astonishingly, these cells have the unique character of being multipotent stem cells. They can differentiate into endothelial cells of capillaries, vascular smooth muscle cells, or fibroblasts when needed, i.e., after a trauma to the vessel during wound healing and angiogenesis (formation of new blood vessels from pre-existing blood vessels). More surprisingly, pericytes found along brain capillaries can differentiate into neuronal cells after a traumatic brain injury.

Skeletal Muscles

Associated with skeletal muscle fibres, some small mononucleated cells are present, which are known as satellite cells, representing the reserve cells or stem cells. These cells remain dormant or quiescent. When there is an injury to the muscle fibres, these cells become activated, divide, grow and fuse to form new muscle fibres. A special aspect of these cells is that their regenerative capability is markedly less. Any minor injury can be corrected but in case of major trauma to the muscle, they cannot repair the damage and scar tissue is formed instead at the injured site.

Use of stem cells in disease treatment, Stem cell Therapies

Many diseases are a result of the defective genetic makeup of a cell. These may be inherited diseases such as diabetes mellitus, haemophilia, leukaemia, thalassemia, hypercholesterolemia, cystic fibrosis, and many more, or can be the acquired ones such as those resulting from DNA damage due to ionizing radiation, toxic substances, i.e., carcinogens, etc. The active area of research nowadays is to use stem cells for the cure of such diseases using stem cell replacement therapy.

Basically, stem cell therapy means the use of healthy stem cells (having a flawless genetic makeup) to treat or prevent disease. In this therapy, stem cells are taken from a healthy individual and then transplanted into the affected person. The best known and fruitful stem cell therapy is hematopoietic stem cell therapy.

Let us go into details using a case of stem cell therapy for the treatment of a thalassemia patient. In a thalassemia patient, bone marrow is defected, having pluripotent hematopoietic stem cells with an altered genetic makeup on chromosome no. 11 in the gene coding for the beta-globin chain of haemoglobin (in case of beta-thalassemia). The patient suffers from haemolysis because of impaired haemoglobin synthesis. This makes the person anaemic and if untreated, it can lead to death. Currently available effective therapy for this disease is a regular blood transfusion from a healthy individual to the thalassemia patient. But this process is not risk-free and may lead to many complications such as the spread of blood-borne diseases and infections, also this does not treat the actual cause of the disease.  Another way to treat this condition is to treat the actual cause. For this purpose, it is devised to take healthy stem cells from the bone marrow of a healthy person and then implant them in the bone marrow of the affected individual. But the actual process is not as easy as it seems.

First of all, there are a series of diagnostic tests to ensure the physical health of a patient, whether he can withstand the transplantation process or its complications if there are any. The patient is prepared mentally for the risks and procedures going to be done in future.

A patient is given chemotherapy that kills the defective bone marrow cells and place is made available for new cells to be transplanted. This chemotherapy has its own complications that sometimes lead to severe effects. This chemotherapy also suppresses the immune system, which is necessary to prevent transplant rejection but at the same time, a person is more prone to infections due to suppressed immunity. Other side effects may include hair loss, diarrhoea, vomiting and nausea etc. Chemotherapeutic agents may cause gastric ulcers. The whole process is called “conditioning”.

After successful conditioning, donor stem cells are infused in the patient’s blood. After infusion, the patient is kept under constant medical care. Different tests are performed to check the success of the transplant. Patients may be given different medicines to manage transplant complications.

Transplant rejection is one of the most common and important hurdles in such treatments. A patient’s immune cells may destroy the newly transplanted cells. Antibodies against transplanted cells may form. This can be overcome by giving the patient different immunosuppressants, but they have their own risks. Also, this method does not have an efficacy of 100% rather the rate of successful transplants is as low as 40% approx. 

Other than thalassemia, different other diseases have been successfully cured in at least one patient like; leukaemia, aplastic anaemia, multiple myeloma, plasma cell disorders, primary amyloidosis, haemoglobinopathies, neuroblastoma, congenital thrombocytopenia etc.

Future Horizons

Stem cells are an active research area in the fields of biotechnology, genetic engineering, medicine and community healthcare for the prevention and treatment of different diseases.

We know that some stem cells known as pericytes can differentiate into neuronal cells. This fact is being used in neurology for the treatment of degenerative and traumatic diseases of the nervous system i.e., Alzheimer’s disease, Parkinson’s disease or even for the regeneration of neuronal tissue after a thromboembolic stroke. Scientists hope to rebuild the nervous system using stem cell therapy. This therapy may be useful in the treatment of spinal cord injuries. Transplanted stem cells can promote axonal growth providing at least partial functional recovery. This technique is being suggested for the treatment of paralysis due to spinal cord injury, but this requires a lot more research.

Stem cell therapy is being used in the field of ophthalmology. A common and prevalent disease in diabetic patients known as “diabetic retinopathy” is the focal point. Some specialized stem cells secrete different growth factors that have protective effects on the retina. Stem cells may reduce the risk of vessel blockage which is the major cause of retinal degeneration and defects, thereby protecting the retina. Currently, stem cell therapy is available only for early retinopathy and not for advanced, proliferating types of this disease. Besides the retina, the cornea (the transparent layer above the eyeball) is an important ophthalmic structure and also prone to trauma or degenerative changes. Stem cell therapy is being used in corneal regeneration. Researchers have proposed that stem cells from an area of the eye known as limbus can be used to treat corneal damage. This therapy has a surprising success rate that many healthcare authorities have approved for use in Europe.

Unlike the smooth and skeletal muscles, which have a regenerative capability, cardiac muscles do not have the regenerative capability at all. When cardiac muscles are injured due to any reason i.e., ischemia, coronary obstruction, arrhythmia or physical trauma etc., the main problem that arises is that the damaged tissue is replaced by scar tissue instead of new cardiac tissue formation. This further leads to weakness of the heart. Scientists are suggesting nowadays to use pluripotent stem cells that can be transplanted into an injured heart so that they can grow into new cardiac tissue.

For many other diseases like acquired immune deficiency syndrome AIDS, osteoporosis, myelomas etc. stem cell therapy is now the main focus of medical researchers. In the near future, scientists aim to eradicate these genetic disorders even before birth during intrauterine life. Hope the future will be free of these lethal disorders!

Summary

Summing up the discussion, let us have a brief review. Stem cells are those which have the ability of self-renewal. These are non-functional immature cells that in times of need differentiate into mature functional cells. According to their potency, they can be divided into totipotent (the true stem cells, also known as embryonic stem cells), pluripotent, multipotent, oligopotent and unipotent stem cells, all other types being called adult stem cells. They are located in various regions of the body. They maintain a reserve of cells that can differentiate into other types so as to maintain a continuous supply of functionally active cells where cells are being lost due to general wear and tear or any physical trauma.

Specific examples of stem cells found in the human body are pluripotent hematopoietic stem cells found in the bone marrow that give rise to blood cells, multipotent pericytes present along continuous capillaries that can develop into vascular endothelial cells, vascular smooth muscle cells and fibroblasts. Occasionally, pericytes present along brain capillaries can give rise to neuronal tissue. Keratinocytes in the skin and hepatocytes in the liver are classic examples of unipotent stem cells. Stem cells are nowadays being used in disease cure and prevention, known as stem cell therapy or stem cell transplant. An advanced and highly successful (relative to others) is a bone marrow transplant. Bone marrow transplant is being carried out to treat thalassemia, leukaemia, aplastic anaemia, multiple myeloma, and plasma cell disorders etc. There are multiple risks including transplant rejection and infections due to suppressed immunity.

Stem cells are an active area of research in biotechnology-like fields. Researchers are trying to figure out the treatment of multiple congenital anomalies and late on-set genetic disorders. In the future, stem cell therapy is being suggested for the treatment of degenerative neuronal diseases like Parkinson’s disease using pericytes. For spinal cord injuries especially paralysis due to spinal damage, stem cell therapy is being proposed. The same is the case in the field of ophthalmology for the treatment of diabetic retinopathy. A major problem in cardiac diseases is that cardiac tissue cannot regenerate. Researchers are trying to implant stem cells so that this problem can be overcome. Future horizons for stem cell therapy are very vast.

Read more about the Cell Structure of Plant and Animal Cells

Frequently Asked Questions

How do you get stem cells?

Stem cells can be obtained from embryonic tissue as well as from adult tissue. Stem cells in an adult body can be found in bone marrow, liver, skin, and gastrointestinal tract, etc. We can get stem cells from these sites of an adult body. Otherwise, they can also be extracted from an embryo.

What are the types of stem cells?

Types of stem cells include:

• Totipotent cells that can differentiate into any cell type and can form viable tissue
• Pluripotent cells can also give rise to any type of tissue but cannot form a viable tissue on its own
• Multipotent cells that can give rise to similar cells only
• Oligopotent cells that can from cells of closely related tissue type
• Unipotent cells that can form cells of only one particular type only    

Which diseases can be cured by stem cells?

There is a long list of diseases that can be cured by stem cells. A few common ones include leukaemias, aplastic anaemia, sickle cell disease, myelodysplastic disorders, osteoporosis, etc. 

What is the best source of stem cells?

Stem cells are found in multiple tissues of an adult as well as an embryo such as skin, bone marrow, GI tract, etc. However, bone marrow is considered to be the best source of stem cells for stem cell therapy.

References

1. Atala A, Lanza R (2012-12-31). Handbook of Stem Cells. Academic Press. p. 452. ISBN 978-0-12-385943-3.
2. Becker AJ, McCulloch EA, Till JE (February 1963). “Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells”. Nature. 197 (4866): 452–4. Bibcode:1963Natur.197..452B. doi:10.1038/197452a0. hdl:1807/2779. PMID 13970094. S2CID 11106827.
3. Siminovitch L, McCulloch EA, Till JE (December 1963). “The distribution of colony-forming cells among spleen colonies”. Journal of Cellular and Comparative Physiology. 62 (3): 327–36. doi:10.1002/jcp.1030620313. hdl:1807/2778. PMID 14086156. S2CID 43875977.