Stem Cells in Regenerative Medicine

Stem Cells And Regenerative Medicine

Stem cells are primitive cells having the following salient features:

1. Stem cells exist in almost all adult tissues called somatic stem cells and are less numerous.
2. Other sources of stem cells are embryos and umbilical cord blood; these stem cells are more numerous.
3. They have a capacity for self-renewal.
4. They can be coaxed into multilineage differentiation (i.e. into any of about 220 types of cells for example Red cells, myocardial fibres, neurons etc).
5. Stem cells can be harvested and grown in the laboratory into a desired cell lineage by transdifferentiation i.e. these cells are pluripotent.
6. Homing of transfused stem cells is their innate ability to travel to the desired site in the body and thus they get engrafted there morphologically and functionally.

Read And Learn More: General Pathology Notes

Sources Of  Stem cells:

The following are three types of sources of stem cells:

1. Resident stem cells:  These stem cells are present in adult tissues where they function to replace cells during the natural course of cell turnover, or when injured.
   • For example, the bone marrow stem cells, epithelial cells in the skin, digestive tract, endothelial cells in blood vessels, hepatocytes, etc.
2. Isolated stem cells:  For clinical application, stem cells are isolated from the organ or site and identified by specific cell surface markers employing flow cytometry.
   • For example, hematopoietic stem cells for bone marrow transplantation.
3. Cultured stem cells: Since for therapeutic purposes, a large number of stem cells are required, expansion in their population can be done in vitro by cell culture. Cultured stem cells may be derived from embryonic stem cells or adult somatic stem cells. Since stem cells can be transdifferentiated, these may be referred to as tissue stem cells rather than assigning them any tissue specificity.

Stem Cell Transplantation Concept:

The role of endogenous stem cells in normal tissue repair by self-renewal as a response to injury has been known to involve proliferation, differentiation, migration of various cell types, and modulation of ECM. For example, In tissue repair in the skin, liver, or digestive system, etc.

• However, in injury to organs such as the heart and brain, there is limited self-renewal of sparse resident stem cells and thus little self-repair.
• It is in such organs and sites that circulating stem cells may contribute to the regenerative response by migration, homing, and differentiation into the organ-specific cells; this forms the basis of regenerative medicine.

In general, stem cell transplantation involves the following three broad concepts:

1. Approach 1:  Undifferentiated or partly differentiated stem cells are injected directly into the target organ intravenously where they undergo differentiation into the desired cell lineage.
   • Systemic injection of stem cells can also be done in which case they home into the damaged tissue under the influence of cytokines.
2. Approach 2:  Fully differentiated cells derived from stem cells are injected into the target tissue.
   • For example, pancreatic islet cells from stem cells in diabetic patients, or cardiac myocytes in ischaemic heart disease.
3. Approach 3:  Injection of growth factors or other drugs to stimulate endogenous stem cell populations may be done.
   • For example, the therapeutic administration of colony-stimulating factor or erythropoietin in hematopoietic disorders stimulates primitive cells to produce the desired mature cell lineage.

Advancements in current technology have made it possible now to use a process of tissue engineering in which the stem cells may be coaxed for in vitro or in situ generation of tissue after combining with certain biomaterials.

Clinical Applications:

Some of the major clinical trials on applications of stem cells underway are in the following directions:

• Bone marrow transplantation:  Haematopoietic stem cells, marrow stromal cells and stem cells sourced from umbilical cord blood, have been used for the treatment of various forms of blood cancers and other blood disorders for over three decades. However, their use for the treatment of other diseases by transdifferentiation is relatively new.
• Nervous system:  Neuron stem cells are capable of generating neurons, astrocytes, and oligodendroglial cells. It may be possible to use these stem cells in neurodegenerative diseases such as Parkinsonism and Alzheimer’s disease, and in spinal cord injury.
•  Diabetes:  Cell-based therapy with islet cells for type I diabetes has been undergoing clinical trials and the results are quite encouraging.
• Heart diseases:  The heart has cardiac stem cells which have capacity to repair the myocardium in ischemic heart disease; the same concept of stem cell replacement of cardiomyocytes can also
  be used for cardiomyopathies.
• Liver:  In the liver, the stem cells are located in the canal of Hering which connects the bile ductules with hepatocytes. These cells can cause the regeneration of hepatocytes in fulminant damage to the liver or in chronic hepatitis.
• Eye:  The cornea of the eye contains stem cells in the region of the limbus. These limbal stem cells have a potential therapeutic use in corneal opacities and damage to the conjunctiva.
• Skin:  In the skin, the stem cells are located in the region of hair follicles and sebaceous glands. These stem cells contribute to the repair of damaged epidermis. While tissue repair in adults normally takes place with the formation of scars and loss of hair, stem cells would elicit a response similar to wound healing in fetal tissue where the repair occurs by regeneration.
• Skeletal muscle:  Although skeletal muscle cells do not divide when injured, stem cells of muscle have the capacity to regenerate.
• Intestines:  Crypts of the intestine contain stem cells that form the villi.
• Lungs:  Clinical trials on the repair of injured lung parenchyma in patients of chronic obstructive pulmonary disease (COPD) with stem cells from the lungs have been going on.

While research on stem cell therapies has offered new strategies for the treatment of many irreversible disorders, it has raised important social and ethical issues on the use of these technologies in organ transplantation and therefore these issues need to be addressed simultaneously.

Stem Cells and Regenerative:

• Medicine Stem cells are primitive cells having the capacity for self-renewal, and multilineage differentiation, can be harvested in vitro and can be modulated to home in the target tissue.
• Embryonic stem cells are more numerous compared to those in adult tissues where they are fewer.
• The concept of stem cell transplantation has 3 approaches: direct injection of stem cells at the target tissues, differentiation of stem cells in vitro followed by injecting them, and stimulation of endogenous stem cells in situ.
• Hematopoietic stem cells and their application in blood cancers and other blood disorders have been known for a long time.
• Besides, major clinical applications of stem cell therapy in recent times are in heart disease, diseases of the nervous system, diabetes, liver, eye and skin.