Frequently Asked Questions: Cell Therapy and Regenerative Medicine

What is regenerative medicine?

Regenerative medicine is a broad definition for innovative medical therapies that will enable the body to repair, replace, restore and regenerate damaged or diseased cells, tissues and organs. Scientists worldwide are engaged in research activities that may enable repair of damaged heart muscle after a heart attack, replacement of skin for burn victims, restoration of movement after spinal cord injury and regeneration of pancreatic tissue to produce insulin for people with diabetes. Regenerative medicine promises to extend healthy life spans and improve the quality of life by supporting and activating the body’s natural healing.

This broad field encompasses a variety of research areas including cell therapy, tissue engineering, biomaterials engineering, growth factors and transplantation science.


What is cell therapy?

The FDA defines cell therapy as, “The prevention, treatment, cure or mitigation of disease or injuries in humans by the administration of autologous, allogeneic or xenogeneic cells that have been manipulated or altered ex vivo.”1 The goal of cell therapy, overlapping with that of regenerative medicine, is to repair, replace or restore damaged tissues or organs.

Cell therapy may take the form of a stem cell transplant such as a hematopoietic cell transplant that is used to restore the blood and immune system of patients with leukemia, lymphoma or other blood disorders.

Activation of the body’s own immune system to fight cancer is referred to as adoptive immunotherapy. This type of cell therapy is most commonly used in the fight against cancer. One type of adoptive immunotherapy treatment artificially increases the number of T killer cells (a form of white blood cell) in the patient and involves collection of patient T cells, ex vivo expansion, then reinfusion to the patient. The result is an increase in the number of T cells and a stronger patient immune response to the cancer.

Regardless of the type of cellular therapy, production of the therapeutic product may require several complex techniques to alter or manipulate the cell. Cell engineering techniques may include:

  • Propagation of cells
  • Expansion of cells
  • Selection of cells
  • Pharmacological treatment of cells
  • Alteration of biological characteristics of cells


What are stem cells and why are they important?

A stem cell is a cell (either adult or embryonic) that is capable of indefinite renewal through cell division and retention of its generic or unspecialized state while at the same time maintaining its potential to give rise to daughter cells of a more specialized type.

Classification of stem cells as totipotent, pluripotent and multipotent describes the breadth of the stem cells’ ability to create specialized cell types. Stem cells represent a continuum or spectrum from embryonic stem cells to adult stem cells. The primary distinguishing factor is plasticity - the stem cell's capacity to differentiate into multiple specialized cell types.

Totipotent stem cells are known as the “master” cells of the body because they have the capacity to differentiate into the 216 specialized cell types that comprise the human body plus the placenta. A fertilized egg is an example of a totipotent cell.

Pluripotent stem cells are highly versatile cells and can give rise to any specialized cell type in the body except those needed to develop a fetus. Embryonic stem cells are pluripotent.

Multipotent stem cells can give rise to several specialized daughter cells but are limited to the particular tissue, organ or physiological system of origin. For example, hematopoietic stem cells can produce many types of blood cells in the circulatory system but cannot differentiate into a brain cell. Hematopoietic stem cells are an example of adult stem cells and are multipotent. Stem cells from umbilical cord blood are also multipotent based on evidence to date.

Take a look at totipotent, pluripotent and multipotent stem cells as they relate to the human development continuum:

Scientists expect enormous benefits from stem cell research and anticipate that it will revolutionize the practice of medicine. Stem cells may even lead to the creation of healthy tissues and organs for replacement of damaged and diseased body parts. Basic research to understand cell differentiation and human development may lead to a greater understanding of how birth defects occur. Stem cells may also be used during development of traditional pharmaceuticals. Stem cells stimulated to differentiate into specialized liver cells could be used for toxicology screening during the evaluation of drug candidates. Although the clinical benefits of cell-based therapies are already being seen, unlocking the full potential of stem cells will take decades of dedicated research. With each day, we move closer to realizing the promises of cell therapy and regenerative medicine.


What are embryonic stem cells?

Embryonic stem cells are derived from embryos, specifically the inner cell mass of a blastocyst, a hollow ball of cells that forms approximately five days after conception. Embryonic stems cells are the most primitive stem cells and as a result contain the most long-term promise for novel cell therapies and tissue regeneration.

Embryonic stem cells are pluripotent, meaning they have the ability to differentiate into any of the 200-plus cell types required by the body. Understanding and controlling embryonic stem cell differentiation and growth will require years of intensive research. Growing these cells in the laboratory is a time-consuming and painstaking process. Scientists must monitor embryonic stem cells closely and provide constant care to ensure continued growth and prevent uncontrolled or spontaneous differentiation.

Most embryonic stem cells used for research today have been donated from excess blastocysts created during in-vitro fertilization. The University of Wisconsin-Madison presents fascinating images on their Stem Cell Research web site.


What are adult stem cells?

Adult (Somatic) stem cells are unspecialized cells that are found in different parts of the body and, depending on the source tissue, have different properties. Adult stem cells are capable of self-renewal and give rise to daughter cells that are specialized to form the cell types found in the original body part.

Adult stem cells are multipotent, meaning that they appear to be limited in the cell types that they can produce based on current evidence. However, recent scientific studies suggest that adult stem cells may have more plasticity than originally thought. Stem cell plasticity is the ability of a stem cell from one tissue to generate the specialized cell type(s) of another tissue. For example, bone marrow stromal cells are known to give rise to bone cells, cartilage cells, fat cells and other types of connective tissue (which is expected), but they may also differentiate into cardiac muscle cells and skeletal muscle cells (this was not initially thought possible).

Hematopoietic stem cells that give rise to all blood and immune cells are today the most understood of the adult stem cells. Hematopoietic stem cells from bone marrow have been providing lifesaving cures for leukemia and other blood disorders for over 40 years. Hematopoietic stem cells are primarily found in the bone marrow but have also been found in the peripheral blood in very low numbers. Compared to adult stem cells from other tissues, hematopoietic stem cells are relatively easy to obtain.

Mesenchymal stem cells are also found in the bone marrow. Mesenchymal stem cells are a mixed population of cells that can form fat cells, bone, cartilage and ligaments, muscle cells, skin cells and nerve cells.

Hematopoietic and stromal stem cell differentiation:4

Umbilical cord blood from newborns is a rich source of hematopoietic stem cells. Research has found that these stem cells are less mature than other adult stem cells, meaning that they are able to proliferate longer in culture and may contribute to a broader range of tissues. Research is ongoing to determine whether umbilical cord stem cells are pluripotent or multipotent and the extent of their plasticity.

Cord blood, which traditionally has been discarded, has emerged as an alternative source of hematopoietic stem cells for the treatment of leukemia, lymphoma and other lethal blood disorders. It has also been used as a life-saving treatment for children with infantile Krabbe’s disease, a lysosomal storage disease that produces progressive neurological deterioration and death in early childhood.

Regardless of the adult stem cells' source – bone marrow, umbilical cord blood or other tissues – these cells are present in minute quantities. This makes identification, isolation and purification challenging. Scientists are currently trying to determine how many kinds of adult stem cells exist and where they are located in the body.


Where do stem cells come from?

Multipotent stem cells for transplant from bone marrow were used experimentally from the 1950’s and 1960's with the work of Thomas and Storb and others, leading to stem cell transplant in the 1970's for hematologic malignancies. This work coined the term “stem cell.” The first human pluripotent cells were isolated in 1998 by Dr. James Thompson at the University of Wisconsin. These cells were isolated from excess embryos obtained from in-vitro fertilization clinics. Subsequently, scientists have isolated stem cells from a variety of adult tissues, but these are multipotent, not pluripotent.

Adult stem cells have been found in the bone marrow, peripheral blood and umbilical cord blood. More recently, scientists have found stem cells in fat, skeletal muscle, skin, blood vessels, retina, liver, pancreas and the brain. Adult stem cells are extremely rare and difficult to identify, isolate and purify.


How is cell therapy being used today and what are the potential uses in the future?

Bone marrow transplants have been used for the past 40 years to regenerate the blood and immune systems of patients with leukemia, lymphoma, severe aplastic anemia or inherited metabolic diseases. Unfortunately, the major limitation with allogenic bone marrow transplants is the availability of matched donors.

Stem cells from Umbilical Cord Blood (UCB) have emerged as an alternative to bone marrow transplants, providing an easily obtainable and readily available source of treatment. UCB transplants may result in a lower incidence of transplant complications, specifically graft-versus-host disease, common in patients receiving a transplant from an unrelated donor. UCB transplants also have less stringent requirements for donor matching compared to bone marrow transplants, increasing the likelihood that an appropriate donor can be found for patients. Until recently, UCB transplants were limited to pediatric patients due to the low cell stem cell dose. But in 2004, researchers demonstrated that combining stem cells from two UCB units could increase the cell dose to extend this lifesaving hematopoietic treatment to adult patients.

In addition to regenerating the blood and immune systems, scientists anticipate that stem cells will be used to replace damaged or diseased tissues and organs. Clinical trials are ongoing to repair scarred or dying heart muscle after a heart attack or during congestive heart failure. On-going research in diabetes is focused on understanding how stem cells might be trained to become the type of pancreatic islet cells that secrete needed insulin. Repair of debilitating spinal cord injuries is also a goal of researchers through the regeneration of neurons, myelin and nerve cells.

As basic research continues, researchers hope to learn how cells replicate and give rise to specialized daughter cells, which may provide insight into inborn cell errors that cause birth defects. Understanding cell signaling pathways can also provide clues to how stem cells are able to hone in on the site of injury to initiate repair of damaged or diseased tissues.

Harnessing stem cells for use as drug delivery systems is another goal of researchers. Stem cells may be able to bring chemotherapeutic agents directly to the targeted cancerous cells. Stem cells may also be used to generate liver cells or other tissues that can be used in screening new drug candidates for safety in pharmaceutical drug development. Using human cells and/or tissues may provide a better model for toxicology testing than the traditional animal models in use today.

Cancer vaccines, a type of adoptive immunotherapy, are in clinical trials for prostrate, breast, ovarian and colorectal cancers. Combining tumor cells from the patient with dendritic cells can lead to a vaccine that will seek out and destroy the cancerous cells. Other adoptive immunotherapies can artificially increase the number of T killer cells (a form of white blood cell) in a cancer patient. This involves collection of patient T cells, ex vivo expansion, then reinfusion to the patient. The result is an increase in the number of T cells and a stronger patient immune response to the cancer.


What obstacles must be overcome before these potential uses will be realized?

Before cell therapies move from basic research laboratories and into widespread use in the clinic, several technical obstacles must be overcome. Scientists must be able to:
  • Understand and control the mechanism of turning undifferentiated cells into specialized cells. This involves identifying the complex signals needed to turn the genes on and off that initiate and govern the differentiation of cells.
  • Identify, isolate and purify different adult stem cell types. Purified and/or expanded stem cells will be required for safe, efficacious treatments.
  • Control the differentiation of stem cells to target cell types needed to treat disease such that sufficient quantities of the correct stem cell or differentiated cell can be generated for treatment.
  • Learn to make stem cell transplants patient-compatible to avoid rejection by the immune system.
  • Demonstrate clinical improvement and normal cell development and function once stem cells have been transplanted into the patient’s body. Stem cells must become integrated with the patient’s own tissues and learn to function as one of the patient’s natural body cells.



  1. Application of Current Statutory Authorities to Human Somatic Cell Therapy Products and Gene Therapy Products, Notice, Oct 14, 1993 (Federal Register). (Notice from the Center for Biologics Evaluation and Research, Center for Drug Evaluation and Research, Center for Devices and Radiological Health, U.S. Food and Drug Administration.)
  2. Where are adult stem cells? Research in Focus – Stem Cell Therapy from the Medical Research Council (MRC) funded through the UK Government through the Office of Science and Technology (OST).
  3. Weiss, Rick. The Power To Divide. National Geographic Magazine, July 13, 2005: p13.
  4. Stem Cell Information; The official National Institutes of Health resource for stem cell research:
  5. International Society of Stem Cell Research: