What are Stem Cells?

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What are Stem Cells?

Types of Stem Cells

Why are Stem Cells Important?

Can doctors use stem cells to treat patients? 

Pros and Cons of Using Stem Cells


What are Stem Cells?

  • Stem cells are unspecialized cells that have not yet “decided” what type of adult cell they will be.
  • They can self-renew and make two new stem cell
  • They can differentiate to make multiple types of cells
  • They ultimately amplify by expanding the number of differentiated & mature cells

There are several different types of stem cells produced and maintained in our system throughout life.  Depending on the circumstances and life cycle stages, these cells have different properties and functions.  There are even stem cells that have been created in the laboratory that can help us learn more about how stem cells differentiate and function.  A few key things to remember about stem cells before we venture into more detail:

  1. Stem Cells are NOT new to science
  2. The definition is relatively simple (see above)
  3. Stem Cells are not all the same.  There are different types of stem cells:
    1. Adult Stem Cells (ASC)
    2. Embryonic Stem Cells (ESC)
    3. Induced Pluripotent Stem Cells (iPS)
  4. Stem Cells are important in tissue homeostasis (maintenance), repair and regeneration
  5. Some Stem Cells (adult) are clinically useful NOW
  6. Other Stem Cells (ESC, iPS) MAY be clinically useful someday – already useful in basic research
  7. All Stem Cell types are important in research
  8. There are both ethical and political issues with the use of some types of stem cells.  UNMC continues to work closely with federal and state legislature as well as the International Society for Stem Cell Research (ISSCR) to promote responsible, transparent, and uniform practices that conform to both federal and state guidelines. 

Stem cells are the foundation cells for every organ and tissue in our bodies. The highly specialized cells that make up these tissues originally came from an initial pool of stem cells formed shortly after fertilization. Throughout our lives, we continue to rely on stem cells to replace injured tissues and cells that are lost every day, such as those in our skin, hair, blood and the lining of our gut.

Source ISSCR

Stem Cell History

Until recently, scientists primarily worked with two kinds of stem cells from animals and humans: embryonic stem cells and non-embryonic "somatic" or "adult" stem cells.  Scientists discovered ways to derive embryonic stem cells from early mouse embryos nearly 30 years ago, in 1981. The detailed study of the biology of mouse stem cells led to the discovery, in 1998, of a method to derive stem cells from human embryos and grow the cells in the laboratory. These cells are called human embryonic stem cells. The embryos used in these studies were created for reproductive purposes through in vitro fertilization procedures. When they were no longer needed for that purpose, they were donated for research with the informed consent of the donor. In 2006, researchers made another breakthrough by identifying conditions that would allow some specialized adult cells to be "reprogrammed" genetically to assume a stem cell-like state. This new type of stem cell is now known as induced pluripotent stem cells (iPSCs).

Source NIH

Types of Stem Cells

Adult Stem Cells (ASCs):

ASCs are undifferentiated cells found living within specific differentiated tissues in our bodies that can renew themselves or generate new cells that can replenish dead or damaged tissue.  You may also see the term “somatic stem cell” used to refer to adult stem cells.  The term “somatic” refers to non-reproductive cells in the body (eggs or sperm).  ASCs are typically scarce in native tissues which have rendered them difficult to study and extract for research purposes.

Resident in most tissues of the human body, discrete populations of ASCs generate cells to replace those that are lost through normal repair, disease, or injury. ASCs are found throughout ones lifetime in tissues such as the umbilical cord, placenta, bone marrow, muscle, brain, fat tissue, skin, gut, etc.   The first ASCs were extracted and used for blood production in 1948.  This procedure was expanded in 1968 when the first adult bone marrow cells were used in clinical therapies for blood disease. 

Studies proving the specificity of developing ASCs are controversial; some showing that ASCs can only generate the cell types of their resident tissue whereas others have shown that ASCs may be able to generate other tissue types than those they reside in.  More studies are necessary to confirm the dispute.

Types of Adult Stem Cells

  • Hematopoietic Stem Cells (Blood Stem Cells)
  • Mesenchymal Stem Cells
  • Neural Stem Cells
  • Epithelial Stem Cells
  • Skin Stem Cells

Embryonic Stem Cells (ESCs):

During days 3-5 following fertilization and prior to implantation, the embryo (at this stage, called a blastocyst), contains an inner cell mass that is capable of generating all the specialized tissues that make up the human body.  ESCs are derived from the inner cell mass of an embryo that has been fertilized in vitro and donated for research purposes following informed consent.  ESCs are not derived from eggs fertilized in a woman’s body. 

These pluripotent stem cells have the potential to become almost any cell type and are only found during the first stages of development.  Scientists hope to understand how these cells differentiate during development.  As we begin to understand these developmental processes we may be able to apply them to stem cells grown in vitro and potentially regrow cells such as nerve, skin, intestine, liver, etc for transplantation. 

Induced Pluripotent Stem Cells (iPSCs)

Induced pluripotent stem cells are stem cells that are created in the laboratory, a happy medium between adult stem cells and embryonic stem cells.  iPSCs are created through the introduction of embryonic genes into a somatic cell (a skin cell for example) that cause it to revert back to a “stem cell like” state.  These cells, like ESCs are considered pluripotent Discovered in 2007, this method of genetic reprogramming to create embryonic like cells, is novel and needs many more years of research before use in clinical therapies.  

NIH

Why are Stem Cells Important?

Stem cells are important for living organisms for many reasons. In the 3- to 5-day-old embryo, called a blastocyst, the inner cells give rise to the entire body of the organism, including all of the many specialized cell types and organs such as the heart, lung, skin, sperm, eggs and other tissues. In some adult tissues, such as bone marrow, muscle, and brain, discrete populations of adult stem cells generate replacements for cells that are lost through normal wear and tear, injury, or disease.

Given their unique regenerative abilities, stem cells offer new potentials for treating diseases such as diabetes, and heart disease. However, much work remains to be done in the laboratory and the clinic to understand how to use these cells for cell-based therapies to treat disease, which is also referred to as regenerative or reparative medicine.

Laboratory studies of stem cells enable scientists to learn about the cells’ essential properties and what makes them different from specialized cell types. Scientists are already using stem cells in the laboratory to screen new drugs and to develop model systems to study normal growth and identify the causes of birth defects.

Research on stem cells continues to advance knowledge about how an organism develops from a single cell and how healthy cells replace damaged cells in adult organisms. Stem cell research is one of the most fascinating areas of contemporary biology, but, as with many expanding fields of scientific inquiry, research on stem cells raises scientific questions as rapidly as it generates new discoveries.

Source NIH

Can doctors use stem cells to treat patients? 

Some stem cells, such as the adult bone marrow or peripheral blood stem cells, have been used in clinical therapies for over 40 years.  Other therapies utilizing stem cells include skin replacement from adult stem cells harvested from hair follicles that have been grown in culture to produce skin grafts.  Other clinical trials for neuronal damage/disease have also been conducted using neural stem cells.  There were side effects accompanying these studies and further investigation is warranted.  Although there is much research to be conducted in the future, these studies give us hope for the future of therapeutics with stem cell research.

Potential Therapies using Stem Cells

Adult Stem Cell Therapies

Bone marrow and peripheral blood stem cell transplants have been utilized for over 40 years as therapy for blood disorders such as leukemia and lymphoma, amongst many others.  Scientists have also shown that stem cells reside in most tissues of the body and research continues to learn how to identify, extract, and proliferate these cells for further use in therapy.  Scientists hope to yield therapies for diseases such as type I diabetes and repair of heart muscle following heart attack.

Scientists have also shown that there is potential in reprogramming ASCs to cause them to transdifferentiate (turn back into a different cell type than the resident tissue it was replenishing). 

Embryonic Stem Cell (ESC) Therapies

There is potential with ESCs to treat certain diseases in the future.  Scientists continue to learn how ESCs differentiate and once this method is better understood, the hope is to apply the knowledge to get ESCs to differentiate into the cell of choice that is needed for patient therapy.  Diseases that are being targeted with ESC therapy include diabetes, spinal cord injury, muscular dystrophy, heart disease, and vision/hearing loss.

Induced Pluripotent Stem Cell Therapies

Therapies using iPSCs are exciting because somatic cells of the recipient can be reprogrammed to en “ESC like” state.  Then mechanisms to differentiate these cells may be applied to generate the cells in need.  This is appealing to clinicians because this avoids the issue of histocompatibility and lifelong immunosuppression, which is needed if transplants use donor stem cells. 

iPS cells mimic most ESC properties in that they are pluripotent cells, but do not currently carry the ethical baggage of ESC research and use because iPS cells have not been able to be manipulated to grow the outer layer of an embryonic cell required for the development of the cell into a human being.

Pros and Cons of Using Various Stem Cells

  • Abundant somatic cells of donor can be used
  • Issues of histocompatibility with donor/recipient transplants can be avoided
  • Very useful for drug development and developmental studies
   Adult Stem Cells Embryonic Stem Cells   Induced Pluripotent Stem Cells  
Pros  
  • Trans differentiate and and reprogramming of these cells is possible but is not well studied
  • Thought to be less likely to be rejected if used in transplants
  • Success has already been demonstrated in various clinical applications 
  • Can maintain and grow for 1 year or more in culture
  • Established protocols for maintenance in culture
  • ESCs are pluripotent cells that can generate most cell types
  • By studying ESCs, more can be learned about the process of development
 
 
  • Abundant somatic cells of donor can be used
  • Issues of histocompatibility with donor/recipient transplants can be avoided
  • Very useful for drug development and developmental studies
  • Information learned from the “reprogramming” process may be transferable for in vivo therapies to reprogram damaged or diseased cells/tissues 
 Cons  
  • Limitations on ASC ability to differentiate are still uncertain; currently thought to be multi or unipotent.
  • Cannot be grown for long periods of time in culture
  • Usually a very small number in each tissue making them difficult to find and purify
  • Currently there is no technology available to generate large quantities of stem cells in culture

  • Process to generate ESC lines is inefficient
  • Unsure whether they would be rejected if used in transplants.
  • Therapies using ESC avenues are largely new and much more research and testing is needed
  • If used directly from the ESC undifferentiated culture prep for tissue transplants, they can cause tumors (teratomas) or cancer development  
  • Methods for ensured reproducibility and maintenance, as differentiated tissues are not certain.
  • Viruses are currently used to introduce embryonic genes and has been shown to cause cancers in mouse studies  
Ethical Concerns
  •   No major ethical concerns have been raised 
 
  • To acquire the inner cell mass the embryo is destroyed
  • Risk to female donors being consented

  •  iPS cells have the potential to become embryos if exposed to the right conditions




 

 



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