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Stem Cells for Cell-Based Therapies

Lauren Pecorino


Stem cells have the potential to cure many human diseases because they are:

  • not yet specialized and can become any type of cell in the human body;
  • regenerative and can be used as an endless supply of live cells for self-repair

This article aims to describe the recent progress in stem cell research and the likely future therapeutic applications of such research.

This article update was sponsored by the the Northwest Association for Biomedical Research. *

December 2012

The world of stem cells

We know the human body comprises many cell types (e.g., blood cells, skin cells, cervical cells), but we often forget to appreciate that all of these different cell types arose from a single cell—the fertilized egg. A host of sequential, awe-inspiring events occur between the fertilization of an egg and the formation of a new individual:

Embryonic stem (ES) cells are also called totipotent cells.
  • The first steps involve making more cells by simple cell division: one cell becomes two cells; two cells become four cells, etc.
  • Each cell of early development is undifferentiated; that is, it is not yet specialized to carry out a specific body function. Cells of early development have the capability to contribute to all of the organs in an individual and are called totipotent.
  • These totipotent cells are embryonic stem (ES) cells and have both the capacity to self-renew, thereby maintaining a continuous supply of stem cells, and the ability to give rise to specialized (differentiated) cell types, such as liver cells or brain cells.
  • Generally, as cells differentiate and become specialized, they lose their ability to divide.
Stem cells also exist in adults and have varying abilities to self-renew.

In addition to embryonic stem cells, stem cells also exist in adults (adult stem cells) that allow specific tissues to regenerate throughout an individual’s life. They also have the ability to self-renew and can give rise to a subset of differentiated cells depending upon the nature of the adult stem cell. Such adult stem cells and lineage-specific progenitor cells (with limited self-renewal ability) have long been known to exist in organs that continually regenerate, such as skin and blood. Some adult stem cells are active all the time (e.g., blood), and some only respond to injury (e.g., hair follicle stem cells) or physiological clues such as hormones (e.g., mammary stem cells).

More recently, however, stem cells have been identified in organs previously thought not to have regenerative capability, including reproductive organs. Female infants were previously thought to be born with a finite number of eggs, but a recent report identified egg stem cells in human ovarian tissue that can form egg cells, called oocytes, in the laboratory.1 Many tissues in the adult body (e.g., neural, muscle, and fat tissues) now appear to contain stem/progenitor cells.

The main use of stem cells in medicine is as a source of donor cells to be used as therapy to replace damaged or missing cells and organs. Stem cells are also useful for creating models of human disease and for drug discovery.

Sources of stem cells

Stem cells can be obtained from several sources:

Scientists can obtain stem cells from multiple sources, including embryos, amniotic fluid, adult tissue, and even cadavers.
  • Spare embryos: Stem cells can come from “leftover” embryos stored at fertility clinics that were not used by couples to have children and may otherwise be discarded.
  • Special purpose embryos: Embryos created by in vitro fertilization (artificially in the lab) for the sole purpose of extracting their stem cells.
  • Cloned embryos: Embryos cloned in labs using the somatic nuclear transfer method in order to harvest their stem cells.
  • Aborted fetuses: Stem cells are taken from fetuses in early development that have been aborted.
  • Amniotic fluid stem cells: Cells isolated from the amniotic fluid of pregnant women.
  • Umbilical cords: Stem cells taken from this frequently discarded after-childbirth tissue hold potential for future research.
  • Adult tissue or organs: Stem cells obtained from the tissue or organs of living adults during surgery.
  • Cadavers: Isolation and survival (up to 20 hours after death) of neural progenitor cells from human post-mortem tissues has been reported and provides an additional source of human stem cells.
  • Induced pluripotent stem cells (iPSC): Adult differentiated cells (e.g. skin) that are reprogrammed in vitro to form embryonic stem cell-like cells. Reprogramming requires the introduction of several specific genes or small molecules into the differentiated cells.2
Adult stem cells and induced pluripotent stem cells are generally viewed as posing less of an ethical dilemma.

Embryonic stem cells must be obtained when an embryo is in early development; that is, when the fertilized egg has divided to form about 1000 cells. These cells are then separated and maintained in a cell culture dish, thereby halting embryonic development toward creating an individual. This is why embryonic stem cell research is the subject of ethical debates, as there is disagreement over when dividing cells should be treated as a person. Utilization of adult stem cells and induced pluripotent stem cells poses less of an ethical dilemma.

Comparing embryonic and adult stem cells

Embryonic stem cells have advantages and disadvantages for therapy.

Adult stem cells and ES cells have both positive and negative attributes that must be carefully weighed.

Embryonic stem cells are:

  • Flexible: They have the potential to create any body cell.
  • Immortal: One cell line can potentially supply endless amounts of cells with carefully defined characteristics.
  • Easily available: Human embryos can be obtained from fertility clinics.

Embryonic stem cells could be:

  • Difficult to control: The method for inducing the specialized cell type needed to treat a particular disease must be defined and optimized. Also, embryonic stem cells can cause tumors.
  • At odds with a patient’s immune system: It is possible that transplanted cells would differ in their immune profile from that of the recipient, causing them to be rejected.
  • Ethically controversial: Those who believe life begins at conception maintain that conducting research on human embryos is unethical even if donors give their consent.

Likewise, adult stem cells also have advantages and disadvantages in therapeutical uses:

Adult stem cells are:

  • Already somewhat specialized, meaning that inducement may be simpler in some cases.
  • Immune hardy: Recipients who receive the products of their own stem cells (autologous stem cells) will not experience immune rejection.3
  • Flexible: Adult stem cells may be used to form other tissue types.
  • Mixed degree of availability: Some adult stem cells are easy to harvest and others, such as neural (brain) stem cells, involve harvesting techniques that can be dangerous to the donor.

Adult stem cells could be:

  • Of minimal quantity: They are difficult to obtain in large quantities.
  • Finite: They don’t live as long in a culture as embryonic stem cells.
  • Genetically unsuitable: Harvested stem cells may carry genetic mutations for disease or become defective during experimentation.
In some cases, adult stem cells from specific organs can give rise to cell types other than the host tissue.

The surprising property of adult stem cells: transdifferentiation

Adult stem cells were thought to be restricted to producing differentiated cells specific for the organ from which they were isolated. Recently, however, several examples have been reported which demonstrate that these stem cells, under certain conditions, can be induced to form other cell types (transdifferentiation). For example:

  • Neural stem cells (NSC) can give rise to blood and skeletal muscle;
  • Bone marrow cells can give rise to muscle, liver cells, and astrocytes.

When NSCs were used to form muscle, no inducers were needed other than co-culturing the cells with muscle progenitor cells (myoblasts) or injecting them into muscle. This holds some promise for cell transplantation therapies, as the experiment suggests that host tissue has some ability to instruct transplanted cells to a desired result.

Stem cells show promise for many clinical applications, including skin replacement and bone marrow therapy.

Stem cell therapies

Embryonic and adult stem cells offer the opportunity to transplant a live source for self-regeneration. Bone marrow transplants (BMT) are a well-known clinical application of adult stem cell transplantation for cancer patients. BMTs can repopulate the marrow and restore the blood’s different cell types after high doses of chemotherapy and/or radiotherapy, which are used to eliminate cancer cells. Adult stem and progenitor cells are being developed for many other clinical applications, such as:


Figure 1. Skin graft grown in the lab from stem cells, Melissa Maggioni, Yann Barrandon’s lab. For more information and educational resources about stem cell research, visit www.eurostemcell.org

Skin replacement
One of the most successful applications in medicine of adult stem cells is skin replacement for burn victims. The ability to maintain adult skin stem cells in culture and to grow and expand skin in vitro has been used in the clinic for decades (Figure 1). Recently, more sophisticated approaches have relied on this knowledge and technique.

A combination gene/stem cell therapy approach has been used to treat a skin blistering disease called Epidermolysis bullosa, a genetic disease caused by a mutation in the laminin 5 gene. In this approach, biopsies from the palm of the patient’s hands are used as a source of skin stem cells. A normal version of the laminin 5 gene can be introduced into these cells in a petri dish. The cells containing the normal version of the gene can then be grown into sheets of cells in the laboratory and grafted onto the patient. Such grafts were shown to be healthy during a one year follow-up period and resulted in some relief for the patient.4

Immunodeficiency diseases
The idea of a combination gene/stem cell therapy approach may be extended for use in induced pluripotent stem cells for other diseases. It has already proven successful for patients with a form of X-linked severe combined immunodeficiency caused by a mutation in the adenosine deaminase gene.5 In such cases, blood stem cells are removed and a normal version of the adenosine deaminase gene is introduced into these cells in the laboratory prior to transplantation into the patient. Patients become immune-competent after treatment.

Proof of this principle was also demonstrated in mice with sickle-cell anemia.6 Induced pluripotent stem cells were created and treated to produce blood stem cells. Gene therapy was used to correct the genetic defect in these cells before performing a bone marrow transplant. Although not yet developed for humans, the approach has potential for the future.

Neural stem cells are being considered as treatments for neurodegenerative diseases and brain/spinal cord injuries.

Cell transplantation for spinal cord injury
Neural stem cells were thought to be strictly embryonic, but many recent findings have proven this incorrect.7 The identification and localization of neural stem cells, both embryonic and adult, have been the major foci of current research. Potential targets of neural stem cell transplants include stroke, traumatic brain injury, neurodegenerative diseases such as Parkinson’s disease, and spinal cord injury.

Christopher Reeve, the actor who famously portrayed Superman, became a victim of spinal cord injury after he fell off a horse. His perpetual support for stem cell research, combined with his celebrity status, brought much public support for stem cell research.

A milestone was hit in 2009 when the US Food and Drug Administration (FDA) granted permission to the company Geron to initiate the world’s first human clinical trial of an embryonic stem cell-based therapy for acute spinal cord injury. Rigorous preclinical testing showed the product (embryonic stem cell-derived oligodendrocyte progenitor cells, which can be thought of as neural-supporting cells) was safe and efficient in improving locomotor skills in animal models.8 The neural-supporting cells produce myelin that insulate nerve cells and allow them to send electric impulses; these cells also make products that support nerve cell growth and survival. Importantly, evidence suggested the product would not cause tumors, a potential side effect of using a product derived from human embryonic stem cells.

However, permission was put on hold after Geron reported the observation of tiny cysts at the injection site in some preclinical experiments in rats. After passing further tests for safety, permission to proceed was granted again. Several patients were treated but, soon after, Geron announced they would discontinue the clinical trials because of financial difficulties, leaving a significant hole in the body of work surrounding the use of stem cell-based therapies for spinal cord injuries.

The eyes have it for stem cell therapies

Scientists are also looking to stem cells for the treatment of eye diseases and blindness.

The first embryonic stem cell trial in Europe has been approved for the treatment of one of the main causes of blindness in young people: Stargardt’s macular dystrophy. This genetic disease causes the loss of cells, called retinal pigment epithelial cells (RPE cells) that lie underneath the retina. These cells support the health of the rods and cones; loss of these cells leads to the loss of rods and cones and, eventually, loss of vision. The trial—initiated by Advanced Cell Technology—will involve the injection of embryonic stem cell-derived RPE cells behind the retinas of human subjects. Thus, another milestone to test the safety of stem cell therapy in a clinical trial is underway.

Adults’ eyes contain limbal stem cells that maintain the health of the cornea, a structure crucial for eye protection and vision. Chemical and thermal burns can result in the loss of these stem cells, as well as normal vision. Transplantation procedures using limbal stem cells from the unaffected eye have been demonstrated to be fairly successful for up to 10 years for those with damaged corneas, though large-scale clinical trials are needed.9

An exciting research report gives hope for further breakthroughs in the application of stem cells for eye disease. Researchers have demonstrated the formation of a three-dimensional optic cup structure (a precursor of the eye) in culture from human embryonic stem cells.10 The fact that the cells organized themselves to form a multi-layered retina with rods and cones that could be then be cryo-preserved moves us one step closer to being able to transplant fully functional retinas.


Figure 2. The first synthetic trachea, developed in the lab of Professor Alexander Seifalian at University College London and seeded with stem cells for implantation into a male patient. The creation of “Claudia’s trachea” utilized a similar process.

Claudia’s trachea and other successes

Recently, patients’ own stem cells have been used to grow organs for transplantation.

The ideal application of stem cells is to use them to replace organs damaged from disease. This has been accomplished in a report that has commonly become known as the story of “Claudia’s trachea.” A 30-year old woman with tuberculosis received a successful tracheal (windpipe) transplant (Figure 2), which was constructed using a donor trachea from a deceased donor (after removing donor cells and antigens), seeding it with cells grown in laboratory from the patient’s own stem cells, and surgically replacing the patient’s diseased windpipe.11 The patient did not require immunosuppressive drugs because the cells of the donated windpipe were her own cells. This approach has been extended to treat several patients with tracheal cancer.

Dentistry may someday involve growing your own teeth

The wearing and decay of teeth over a lifetime is inevitable, but the potential for stem cells to replace teeth may not be too far in the distant future. The production of a tooth using non-dental stem cells has been demonstrated in adult mice.13 First, non-dental stem cells were used to construct an embryonic primordium (defined as an organ in its earliest recognizable stage of development) in vitro, and transplantation of the primordium to the mouth of an adult mouse was then shown to form a tooth. The most successful source of non-dental stem cells tested was derived from adult bone marrow, which suggests that growing teeth from a patient’s own stem cells may someday become a reality.

Use of stem cells for drug discovery

Induced pluripotent stem cells may provide a valuable, and renewable, tool in toxicity studies for clinical trials.

Liver and heart toxicity problems account for about 30% of drugs that fail in early stage clinical trials, indicating a need for more efficient and successful means of testing drugs for toxicity before clinical trials. Induced pluripotent stem cells can be an important and limitless source of human liver and heart cells for toxicity studies.14 iPSC-derived heart cells are already being used for this purpose but obstacles still remain for generating fully functional iPSC-derived liver cells. The generation of iPSC cells from patients with specific diseases holds promise for better models of each disease and can include different genotypes. Such cells have been created for Huntington’s disease, Juvenile diabetes, spinal muscular atrophy, and severe combined immunodeficiency.15

Future directions

The generation of new neurons in the adult brain is limited. However, self-repair of neuronal cell death has been recently demonstrated in mice, suggesting that stem cells normally residing in the brain might be able to be stimulated by inducers in a manner similar to how we induce our immune system by vaccination.3 Such a process would bypass the need for cell transplantation. A search has begun to discover regenerative drugs that can prompt endogenous stem cells to differentiate in vivo and repopulate lost or diseased cells in conditions such as stroke. Some regenerative drugs are already available and others are actively being developed. For example, eltrombopag (Promacta/Revolade) is a small molecule that stimulates the production of platelets from blood progenitor cells, and compounds that stimulate bone differentiation from stem cells are being developed as drugs for promoting bone growth. In the meantime, we eagerly await the elongation of the list of regenerative drugs.

Large-scale clinical trials are needed to ensure the safety and efficieny of stem cell therapies.

Research is leading us closer to the routine and broad use of stem cells in the clinic but, before this can become a reality, large scale clinical trials for safety and efficiency are needed. Some of the work described above is demonstrated in mice or in a few human case studies. With the initiation of clinical trials such as those for spinal cord injury and Stargardt’s macular dystrophy, the journey has begun, but it is important to realize that claims of stem cell wonder treatments are not to be trusted without vetted data from clinical trials and the approval of bodies such as the Food and Drug Administration.

Scientists and stem cell research

The majority of Americans are in favor of medical research that utilizes stem cells from human embryos.

Scientists believe that stem-cell research could lead to cures for myriad diseases afflicting humans. Anti-abortion groups, some religious groups, and conservative citizens say that using cells from embryos is immoral because it destroys life. However, a recent poll published in the New England Journal of Medicine showed that 6 out of 10 (62%) Americans believe that medical research involving stem cells obtained from human embryos is morally acceptable and favor conducting medical research that uses stem cells from human embryos, with the majority saying that it should be funded by the federal government.16 The Obama Administration has lifted former-President George W. Bush’s previous restrictions on funding, and the legality of that decision was upheld by federal courts, but the future degree of such funding lies in political hands.

Most scientists do not support applications for human reproductive cloning; that is, they do not want any embryos altered during stem cell research to develop past a defined stage. They agree with governments and concerned citizens that it should be banned worldwide. However, they do want the opportunity to continue stem cell research for clinical applications under appropriate regulation and legislation with the hope of alleviating human suffering.

Dr. Lauren Pecorino received her Ph.D. in Cellular and Developmental Biology from the State University of New York at Stony Brook. She carried out a post-doctoral tenure as an EMBO Fellow at the Ludwig Institute for Cancer Research, London, England, working on limb regeneration. Currently, she is a Biochemistry Programme Leader at the University of Greenwich, U.K. She is the author of the book,’ Why Millions Survive Cancer’ (Oxford University Press, 2011) and the textbook, Molecular Biology of Cancer: Mechanisms,Targets, and Therapeutics (Oxford University Press, 3rd ed 2012).

*This project was supported by Science Education Partnership Award #R25OD011138 to NWABR from the National Center for Research Resources and the Division of Program Coordination, Planning, and Strategic Initiatives of the National Institutes of Health.

Stem Cells for Cell-Based Therapies

National Institutes of Health (NIH) Stem Cell Information

Official resource about research, ethical issues, federal policies for using embryonic stem cells, current research, and FAQs.

NewScientist: Stem Cells

An in-depth topical guide with recent news articles, multimedia content, and current information on the continuing controversy and promise of stem cells.

ScienceDaily: Stem Cells

Up-to-date information and current articles about novel stem cell technologies and recent advances in stem cell research.

Scientific American

Get the latest in stem cell research, news, and technologies from science experts at Scientific American.


The nation’s largest not-for-profit public education and advocacy alliance. Research!America advocates for increased funding for scientific research organizations and a regulatory climate that promotes growth in industry research and development.

National Stem Cell Foundation

The National Stem Cell Foundation is a non-profit organization that supports adult stem cell research and clinical trials that have the potential to treat or cure conditions and diseases affecting people worldwide.

Do No Harm

Against the use of embryonic stem cells for research purposes? Join the Coalition of Americans for Research Ethics and voice your opinion on stem cell research and alternatives. http://www.stemcellresearch.org/



Teaching Resources from the Northwest Association for Biomedical Research (NWABR)

The Northwest Association for Biomedical Research (NWABR) strengthens public trust in research through education and dialogue. Its diverse membership spans academic, industry, non-profit research institutes, health care, and voluntary health organizations. Through membership and extensive education programs, it fosters a shared commitment to the ethical conduct of research and ensures the vitality of the life sciences community.

Stem Cell Research
This unit, which was designed by teachers in conjunction with scientists, ethicists, and curriculum developers, explores the scientific and ethical issues involved in stem cell research. While exploring the ethics of stem cell research, students will develop an awareness of the many shades of gray that exist among positions of stakeholders in the debate.

Planaria Laboratory Activity

Students use planaria as a model organism for understanding stem cell concepts, including stem cell potency. Educator’s lesson plan and student activity.
http://www.nwabr.org/education/pdfs/STEM_CELL_PDF/Planaria_Teacher.pdf http://www.nwabr.org/education/pdfs/STEM_CELL_PDF/Planaria_Student.pdf

Learn.Genetics: University of Utah Genetic Science Learning Center

Teacher resources, lesson plans, and activities to engage students in learning about the changing landscape of stem cell science. Also includes an archive of earlier materials.


More than 100 stem cell educational resources and teaching tools, fully searchable using filters and keywords. Ideal for teachers, science centers and museums, outreach, and more.

Stem Cell Science Education

A variety of resources on stem cell bioscience education, including curricula, case studies, lesson plans, modules, web activities, and teaching/learning standards.

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  8. Kierstead, H.S., et al. (2005). HESC-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after SC injury. J Neuroscience 25 (19): 4694-4705.
  9. Rama, P. et al., (2010) Limbal stem-cell therapy and long-term corneal regeneration. N. Engl. J. Med. 363:147-155.
  10. Nakano, T., et al. (2012) Self-formation of optic cups and storable stratified neural retina from human ESCs. Cell Stem Cell 10:771-785.
  11. Macchiarini, P., Jungebluth, P., Go, T., Asnaghi, M.A., Rees, L.E., Cogan, T.A., Dodson, A., Martorell, J., Bellini, S., Parnigotto, P.P. et al., (2008) Clinical transplantation of a tissue-engineered airway. The Lancet 372:2023-2030.
  12. Olausson, M., et al. (2012). Transplantation of an allogeneic vein bioengineered with autologous stem cells: a proof-of-concept study. The Lancet 380:230-237.
  13. Ohazama, A., Modino, S.A.C., Miletich, I., and Sharpe, P.T. (2004) Stem-cell-based tisuue engineering of murine teeth. J Dent Res 83:518-522.
  14. Hook, L.A. (2011) Stem cell technology for drug discovery and development. Drug Discov. Today 17:336-342.
  15. HD iPSC Consortium. 2012 Induced Pluripotent Stem Cells from Patients with Huntington’s Disease Show CAG-Repeat-Expansion-Associated Phenotypes. Cell Stem Cell 11:264-278
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  17. Blendon, R.J., Kim, M.K., and Benson, J.M. (2011). The public, political parties, and stem-cell research. N Engl. J. Med. 365:1853-1856.


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