Cell therapy

Definition

Cell therapy is the transplantation of human or animal cells to replace or repair damaged tissue and/or cells.

Origins

The theory behind cell therapy has been in existence for several hundred years. The first recorded discussion of the concept of cell therapy can be traced to Phillippus Aureolus Paracelsus (1493–1541), a German-Swiss physician and alchemist who wrote in his Der grossen Wundartzney ("Great Surgery Book") in 1536 that "the heart heals the heart, lung heals the lung, spleen heals the spleen; like cures like." Paracelsus and many of his contemporaries agreed that the best way to treat an illness was to use living tissue to restore the ailing. In 1667, at a laboratory in the palace of Louis XIV, Jean-Baptiste Denis (1640–1704) attempted to transfuse blood from a calf into a mentally ill patient—and since blood transfusion is, in effect, a form of cell therapy, this could be the first documented case of this procedure. However, the first recorded attempt at non-blood cellular therapy occurred in 1912 when German physicians attempted to treat children with hypothyroidism , or an underactive thyroid, with thyroid cells.

In 1931, Dr. Paul Niehans (1882–1971), a Swiss physician, became known as "the father of cell therapy" quite by chance. After a surgical accident by a colleague, Niehans attempted to transplant a patient's severely damaged parathyroid glands with those of a steer. When the patient began to rapidly deteriorate before the transplant could take place, Niehans decided to dice the steer's parathyroid gland into fine pieces, mix the pieces in a saline solution, and inject them into the dying patient. Immediately, the patient began to improve and, in fact, lived for another 30 years.

Benefits

Cell therapy has been used successfully to rebuild damaged cartilage in joints, repair spinal cord injuries, strengthen a weakened immune system, treat autoimmune diseases such as AIDS , and to help patients with neurological disorders such as Alzheimer's disease, Parkinson's disease , and epilepsy . Further uses have shown positive results in the treatment of a wide range of chronic conditions such as arteriosclerosis, congenital defects, and sexual dysfunction . The therapy has also been used to treat cancer patients at a number of clinics in Tijuana, Mexico, although this application has not been well supported with controlled clinical studies.

In September 2002, clinical trials were announced involving a French biotechnology company to develop cell therapy to treat heart disease . The cell therapy program would test the theory that cell therapy could reverse the damage done to heart muscle during a heart attack , stopping progression to congestive heart failure. Another new study was working on ways to use stem cells for patients with diabetes. New trials in 2002 showed promise for tissure regeneration of b-cells, restoring the ability of the pancreas to secrete insulin.

Description

Cell therapy is, in effect, a type of organ transplant which has also been referred to as live cell therapy, xeno-transplant therapy, cellular suspensions, glandular therapy, or fresh cell therapy. The procedure involves the injection of either whole fetal xenogenic (animal) cells (e.g., from sheep, cows, pigs, and sharks) or cell extracts from human tissue. The latter is known as autologous cell therapy if the cells are extracted from and transplanted back into the same patient. Several different types of cells can be administered simultaneously.

Just as Paracelsus' theory of "like cures like," the types of cells that are administered correspond in some way with the organ or tissue in the patient that is failing. No one knows exactly how cell therapy works, but proponents claim that the injected cells travel to the similar organ from which they were taken to revitalize and stimulate that organ's function and regenerate its cellular structure. In other words, the cells are not species specific, but only organ specific. Supporters of cellular treatment believe that embryonic and fetal animal tissue contains active therapeutic agents distinct from vitamins, minerals, hormones, or enzymes.

Swedish researchers have successfully transplanted human fetal stem cells into human recipients, and the procedure is being investigated further as a possible treatment for repairing brain cells in Parkinson's patients. However, because the cells used in these applications must be harvested from aborted human fetuses, there is an ethical debate over their use.

Currently, applications of cell therapy in the United States are still in the research, experimental, and clinical trial stages. The U.S. Food and Drug Administration has approved the use of one cellular therapy technique for use in repairing damaged knee joints. The procedure involves removing healthy chondrocyte cells, the type of cell that forms cartilage, from the patient, culturing them in a laboratory for three to four weeks, and then transplanting them back into the damaged knee joint of the patient.

PAUL NIEHANS 1882–1971

Paul Niehans was born and raised in Switzerland. His father, a doctor, was dismayed when he entered the seminary, but Niehans quickly grew dissatisfied with religious life and took up medicine after all. He first studied at Bern, then completed an internship in Zurich.

Niehans enlisted in the Swiss Army in 1912. When war erupted in the Balkans, Niehans set up a hospital in Belgrade, Yugoslavia. The war provided him the opportunity to treat numerous patients, gaining a firsthand knowledge of the body and its workings.

Since 1913, Niehans had been intrigued with Alexis Carrel's experiments concerning the adaptive abilities of cells, though Niehans himself specialized in glandular transplants and by 1925 was one of the leading glandular surgeons in Europe.

Niehans referred to 1931 as the birth year of cellular therapy. That year, he treated a patient suffering from tetany whose parathyroid had been erroneously removed by another physician. Too weak for a glandular transplant, the patient was given injections of the parathyroid glands of an ox, and she soon recovered. Niehans made more injections, even experimenting on himself, and reported he could cure illnesses through injections of live cells extracted from healthy animal organs. He believed adding new tissue stimulated rejuvenation and recovery.

Niehans treated Pope Pious XII with his injections and was nominated to the Vatican Academy of Science following the pope's recovery.

Niehans remained a controversial figure throughout his life. As of 2000, the Clinique Paul Niehans in Switzerland, founded by his daughter, continued his work.

Lisa Frick

Preparations

There are several processes to prepare cells for use. One form involves extracting cells from the patient and then culturing them in a laboratory setting until they multiply to the level needed for transplant back into the same patient. Another procedure uses freshly removed fetal animal tissue, which has been processed and suspended in a saline solution. The preparation of fresh cells then may be either injected immediately into the patient, or preserved by being freeze-dried or deep-frozen in liquid nitrogen before being injected. Cells may be tested for pathogens, such as bacteria, viruses, or parasites, before use.

Precautions

Patients undergoing cell therapy treatments which use cells transplanted from animals or other humans run the risk of cell rejection, in which the body recognizes the cells as a foreign substance and uses the immune system's T-cells to attack and destroy them. Some forms of cell therapy use special coatings on the cells designed to trick the immune system into recognizing the new cells as native to the body.

There is also the chance of the cell solution transmitting bacterial or viral infection or other disease and parasites to the patient. Careful screening and testing of cells for pathogens can reduce this risk.

Many forms of cell therapy in the United States are still largely experimental procedures. Patients should approach these treatments with extreme caution, should inquire about their proven efficacy and legal use in the United States, and should only accept treatment from a licensed physician who should educate the patient completely on the risks and possible side effects involved with cell therapy. These same cautions apply for patients interested in participating in clinical trials of cell therapy treatments.

Side effects

Because cell therapy encompasses such a wide range of treatments and applications, and many of these treatments are still experimental, the full range of possible side effects of the treatments are not yet known. Anaphylactic shock (severe allergic reaction), immune system reactions, and encephalitis (inflammation of the brain) are just a few of the known reported side effects in some patients to date.

Side effects of the FDA approved chondrocyte cell therapy used in knee joint repair may include tissue hypertrophy, a condition where too much cartilage grows in the cell-transplanted joint and the knee joint begins to stiffen.

Research & general acceptance

There is a growing debate in the medical community over the efficacy and ethical implications of cell therapy. Much of the ethical debate revolves around the use of human fetal stem cells in treatment, and the fact that these cells must be harvested from aborted fetuses.

In 2002, a new study attempted to increase the amount of stem cells that could be used for a Parkinson's disease treatment while decreasing the amount of fetal tissue required. With careful timing of the cells' harvesting and development, scientists successfully harvested more cells that proved useful by using less tissue.

While some cell therapy procedures have shown proven success in clinical studies, others are still largely unproven, including cell therapy for cancer treatment. Until more large, controlled clinical studies are performed on these procedures to either prove or disprove their efficacy, they will remain fringe treatments.

Training & certification

Cell therapy should only be performed by a licensed physician with experience in prescribing and administering the treatment. Surgical cell therapy procedures, such as the arthroscopic surgery involved in chondrocyte cell therapy, should only be performed by a surgical specialist.

Resources

BOOKS

Sheridan, William, and George Morstyn. Cell Therapy: Stem Cell Transplantation, Gene Therapy, and Cellular Immunotherapy. Cambridge, UK: Cambridge University Press, 1996.

PERIODICALS

"Cardiac Cell Therapy Collaboration Forged." Heart Disease Weekly (September 29, 2002):15.

"In vitro-expanded Neural Stem Cell Therapy Improves Rats." Stem Cell Week (September 30, 2002):2.

Lawrence, David. "Stem-cell Researchers Offer Possible Therapy for Diabetes." The Lancet (July 20, 2002):233.

Sinha, Gunjan. "On the Road to Recovery: Fetal Pig Cell Therapy has put Parkinson's Patient Jim Finn back in the Driver's Seat." Popular Science 255, no. 4 (October 1999): 77-82.

ORGANIZATIONS

Center for Cell and Gene Therapy. Baylor College of Medicine. 1102 Bates St, Suite 1100, Houston, Texas 77030-2399. (713) 770-4663. http://www.bcm.tmc.edu/genetherapy.

Paula Ford-Martin

Teresa G. Odle

Cell Therapy

Definition

Cell therapy is the transplantation of human or animal cells to replace or repair damaged tissue and/or cells.

Purpose

Cell therapy has been used successfully to rebuild damaged cartilage in joints, repair spinal cord injuries, strengthen a weakened immune system, treat autoimmune diseases such as AIDS, and help patients with neurological disorders such as Alzheimer's disease, Parkinson's disease, and epilepsy. Further uses have shown positive results in the treatment of a wide range of chronic conditions such as arteriosclerosis, congenital defects, and sexual dysfunction. The therapy has also been used to treat cancer patients at a number of clinics in Tijuana, Mexico, although this application has not been well supported with controlled clinical studies.

Description

Origins

The theory behind cell therapy has been in existence for several hundred years. The first recorded discussion of the concept of cell therapy can be traced to Phillippus Aureolus Paracelsus (1493–1541), a German-Swiss physician and alchemist who wrote in his Der grossen Wundartzney ("Great Surgery Book") in 1536 that "the heart heals the heart, lung heals the lung, spleen heals the spleen; like cures like." Paracelsus and many of his contemporaries agreed that the best way to treat an illness was to use living tissue to restore the ailing. In 1667, at a laboratory in the palace of Louis XIV, Jean-Baptiste Denis (1640–1704) attempted to transfuse blood from a calf into a mentally ill patient—and since blood transfusion is, in effect, a form of cell therapy, this could be the first documented case of this procedure. However, the first recorded attempt at non-blood cellular therapy occurred in 1912 when German physicians attempted to treat children with hypothyroidism, or an under-active thyroid, with thyroid cells.

In 1931, Dr. Paul Niehans (1882–1971), a Swiss physician, became known as "the father of cell therapy" quite by chance. After a surgical accident by a colleague, Niehans attempted to transplant a patient's severely damaged parathyroid glands with those of a steer. When the patient began to rapidly deteriorate before the transplant could take place, Niehans decided to dice the steer's parathyroid gland into fine pieces, mix the pieces in a saline solution, and inject them into the dying patient. Immediately, the patient began to improve and, in fact, lived for another 30 years.

Cell therapy is, in effect, a type of organ transplant which has also been referred to as "live cell therapy," "xenotransplant therapy," "cellular suspensions," "glandular therapy," or "fresh cell therapy." The procedure involves the injection of either whole fetal xenogenic (animal) cells (e.g., from sheep, cows, pigs, and sharks) or cell extracts from human tissue. The latter is known as autologous cell therapy if the cells are extracted from and transplanted back into the same patient. Several different types of cells can be administered simultaneously.

Just as Paracelsus's theory of "like cures like," the types of cells that are administered correspond in some way with the organ or tissue in the patient that is failing. No one knows exactly how cell therapy works, but proponents claim that the injected cells travel to the similar organ from which they were taken to revitalize and stimulate that organ's function and regenerate its cellular structure. In other words, the cells are not species specific, but only organ specific. Supporters of cellular treatment believe that embryonic and fetal animal tissue contain active therapeutic agents distinct from vitamins, minerals, hormones, or enzymes.

Swedish researchers have successfully transplanted human fetal stem cells into human recipients, and the procedure is being investigated further as a possible treatment for repairing brain cells in Parkinson's patients. However, because the cells used in these applications must be harvested from aborted human fetuses, there is an ethical debate over their use.

Currently, applications of cell therapy in the United States is still in the research, experimental, and clinical trial stages. The U.S. Food and Drug Administration has approved the use of one cellular therapy technique for repairing damaged knee joints. The procedure involves removing healthy chondrocyte cells, the type of cell that forms cartilage, from the patient, culturing them in a laboratory for three to four weeks, and then transplanting them back into the damaged knee joint of the patient.

PAUL NIEHANS (1882–1971)

Paul Niehans was born and raised in Switzerland. His father, a doctor, was dismayed when he entered the seminary, but Niehans quickly grew dissatisfied with religious life and took up medicine after all. He first studied at Bern, then completed an internship in Zurich.

Niehans enlisted in the Swiss Army in 1912. When war erupted in the Balkans, Niehans set up a hospital in Belgrade, Yugoslavia. The war provided him the opportunity to treat numerous patients, gaining a firsthand knowledge of the body and its workings.

Since 1913, Niehans had been intrigued with Alexis Carrel's experiments concerning the adaptive abilities of cells, though Niehans himself specialized in glandular transplants and by 1925 was one of the leading glandular surgeons in Europe.

Niehans referred to 1931 as the birth year of cellular therapy. That year, he treated a patient suffering from tetany whose parathyroid had been erroneously removed by another physician. Too weak for a glandular transplant, the patient was given injections of the parathyroid glands of steer, and she soon recovered. Niehans made more injections, even experimenting on himself, and reported he could cure illnesses through injections of live cells extracted from healthy animal organs. He believed adding new tissue stimulated rejuvenation and recovery.

Niehans treated Pope Pious XII with his injections and was nominated to the Vatican Academy of Science following the pope's recovery.

Niehans remained a controversial figure throughout his life. As of 2000, the Clinique Paul Niehans in Switzerland, founded by his daughter, continued his work.

Preparations

There are several processes to prepare cells for use. One form involves extracting cells from the patient they are to be used on and then culturing them in a laboratory setting until they multiply to the level needed for transplant back into the patient. Another procedure uses freshly removed fetal animal tissue, which has been processed and suspended in a saline solution. The preparation of fresh cells then may be either injected immediately into the patient, or preserved by being freeze-dried or deep-frozen in liquid nitrogen before being injected. Cells may be tested for pathogens, such as bacteria, viruses, or parasites, before use.

Precautions

Patients undergoing cell therapy treatments which use cells transplanted from animals or other humans run the risk of cell rejection, in which the body recognizes the cells as a foreign substance and uses the immune system's T-cells to attack and destroy them. Some forms of cell therapy use special coatings on the cells designed to trick the immune system into recognizing the new cells as native to the body.

There is also the chance of the cell solution transmitting bacterial or viral infection or other disease and parasites to the patient. Careful screening and testing of cells for pathogens can reduce this risk.

Many forms of cell therapy in the United States are still largely experimental procedures. Patients should approach these treatments with extreme caution, should inquire about their proven efficacy and legal use in the United States, and should only accept treatment from a licensed physician who should educate the patient completely on the risks and possible side effects involved with cell therapy. These same cautions apply for patients interested in participating in clinical trials of cell therapy treatments.

Side effects

Because cell therapy encompasses such a wide range of treatments and applications, and many of these treatments are still experimental, the full range of possible side effects of the treatments are not yet known. Anaphylactic shock (severe allergic reaction), immune system reactions, and encephalitis (inflammation of the brain) are just a few of the known reported side effects in some patients.

Side effects of the FDA-approved chondrocyte cell therapy used in knee joint repair may include tissue hypertrophy, a condition where too much cartilage grows in the joint where the cells were transplanted to and the knee joint begins to stiffen.

Research and general acceptance

There is a growing debate in the medical community over the efficacy and ethical implications of cell therapy. Much of the ethical debate revolves around the use of human fetal stem cells in treatment, and the fact that these cells must be harvested from aborted fetuses.

While some cell therapy procedures have had proven success in clinical studies, others are still largely unproven, including cell therapy for cancer treatment. Until more large, controlled clinical studies are performed on these procedures to either prove or disprove their efficacy, they will remain fringe treatments.

Resources

PERIODICALS

Sinha, Gunjan. "On the Road to Recovery: Fetal pig cell therapy has put Parkinson's patient Jim Finn back in the driver's seat." Popular Science 255, no. 4 (Oct 1999): 27.

ORGANIZATIONS

Center for Cell and Gene Therapy. Baylor College of Medicine. 1102 Bates St, Suite 1100, Houston, Texas 77030-2399. (713) 770-4663. 〈http://www.bcm.tmc.edu/genetherapy〉.

KEY TERMS

Anaphylactic shock— A severe allergic reaction that causes blood pressure drop, racing heart, swelling of the airway, rash, and possibly convulsions.

Culturing— To grow cells in a special substance, or media, in the laboratory.

Encephalitis— Inflammation of the brain.