Probably the best way to cover the topic of stem cell regulation is by questions and answers that are short and to the point. The answers can then go into more detail if necessary.
Q: Who reviews the production and marketing of stem cells?
A: The Food & Drug Association overlooks any therapies that are stem cell based and involve the transplantation of human cells into humans.
Q: Why is it important to understand regulation of stem cells?
A: Researchers in the biotech and pharmaceutical industries as well as doctors need to know basic knowledge about what criteria must be followed before stem cells can be used clinically. Additional knowledge about efficacy of the therapies should also be understood.
Q: When did the first stem-cell based therapies start?
A: Surprisingly to most people, the first stem cell based therapies began with bone marrow transplants back in 1968.
Q: What exactly falls under the category of regulated stem cell therapies?
A: Two types of stem cell applications – 1) embryonic pluripotent stem cells, and 2) adult multipotent stem cells.
These must be used for transplantation in humans with medical conditions that will require the repair of cells, tissues and organs. The final product may not contain actual stem cells but it is still regulated. Also, the stem cells may differentiate in a culture before they are injected into a human. These would also be regulated.
In these cases, stem cell products are named biologic products, drugs, devices or xenotransplantation products, and human cells, tissues, and cellular and tissue- based products.
If stem cells are highly processed, they are subject to the Public Health Safety Act, Section 351. This law requires the submission of an investigational new drug application to the FDA before it can be used in humans. The same law applies to any stem cell product that is used for something other than what its normal function is, including metabolic purposes.
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Q: What types of donor requirements are there for using stem cells?
A: Donors must not have any infectious disease or any type of genetic disease.
Q: What types of questions are asked in the application to the FDA?
A: The application is lengthy but includes questions such as whether or not contamination can occur during tissue processing, what types of cells are used, questions on how pure the final product is, and how safe and effective it will be once injected into or used in a human.
The FDA is also concerned about the transfer of any disease from one person to another with the cells. Screening for communicable disease is necessary and must be outlined in the protocols.
The only exception for screening and testing is when gametes are donated by the recipient’s sexually intimate partner. The other option on the gametes is when extra embryos from in vitro fertilization clinics are provided. In these cases there has to be screening and testing of them.
Q: Is there any requirement for donors or donated tissue to be tested for any predisposition to any serious genetic disease?
A: At this time there is not. Technically someone could donate their stem cells to be used for cardiomyopathy but have a family history of cardiac problems. Or someone could carry a genetic defect that causes one of many types of anemia, and their stem cells would be inappropriate for the use of building up the blood after someone has received chemotherapy and radiation treatments for cancer. In these cases, the person receiving the stem cells would be trading in one disease for another one.
Q: Since there’s a lag time in between taking donor blood samples and the time that they are used, what types of rules does the FDA have on this?
A: Donor blood samples must be clearly labeled and archived so that if there was an issue with a genetic disease or an infection, the sample can be identified quickly. Donor contact information should also be kept current in case rescreening is necessary. All information that is stored on donors must be compliant with the HIPAA laws (Health Insurance Portability and Accountability Act).
Q: When is contamination an issue with stem cells?
A: It’s only when stem cell products are banked, transported, or processed in facilities with other cellular or tissue-based products that this is an issue. In these cases, there has to be rules on “current good tissue practices” that apply for pre-marketing approval and for clinical Phase 1 trials.
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Q: What rules are there for stem cell based products grown in cultures?
A: This is a good question as the use of nonhuman serum may play a role in the development of these stem cells. Often, fetal calf serum is used, and it must be clear of bovine spongiform encephalopathy. This requires a certification from a country that tests for the disease.
Cultures may also include what’s called xenogeneic feeder cells. These are usually from mice. The FDA has stated that the mouse embryonic feeder cells will be allowed in stem cell transplants in humans but they will need additional testing in order to minimize the risk of transmitting infectious diseases from animals.
It’s common now that human embryonic stem cell lines are derived from human cells as feeders and human and recombinant serum components. Human feeder cells will still have to be screened for safety purposes.
Stem cell based products that are derived from human embryonic stem cells usually require manipulation, expansion and culturing time in the laboratory. Research studies have found that over the course of one year, the growth of human embryonic stem cells are stable karyotypically (the chromosomal characteristics of the cell) but there are other problems that occur.
The copy number, mitochondrial DNA, sequence and gene promoter methylation is not stable. Scientists have discovered a process called viral seed-lot systems that help keep the genes stable. What these do is set the permissible number of revisions to a minimum before, during and after their differentiation into tissues for transplants.
Q: What about the purity of the cell or tissues that are produced from stem cells? What types of regulations are necessary for this?
A: In order for stem cell products to work successfully, the cells have to be pure and the right type of cells. To obtain this purity, the history of the cells in the product is important. There are identifying markers (with different staining techniques) that may be used to determine the purity of the product and seeing the actual function of the cells will help too.
For example, cells either produce insulin or they don’t – and that’s important for diabetic patients. Studies must be done to monitor the function of the cells and how long they last after transplantation.
There are times when cell mixtures are desirable because all the different types of cells will then differentiate. Thus, a product does not have to be 100% one type of cell in order to be considered pure. A product is considered contaminated if it has undesirable cell types in its composition as well as cells from feeder layers.
Q: How does the FDA determine whether or not the stem cell-based product is safe and effective in humans?
A: This is done through animal experiments. When looking at whether or not stem cells restore insulin levels in blood, the pancreas does not have to be the site of the stem cell transplantation. Stem cells will often travel to the site where they are needed as in the case of insulin-producers. These cases will require biologic distribution studies that track the location of the stem cells in the body. The longevity of the cells should also be studied.
However, there are cases where site specific integration of cells is necessary such as in Parkinson’s disease. In this case, the dopaminergic neurons are located in the brain.
Q: Is it possible that stem cell-based therapies will cause tumors and if so, how does the FDA prevent this from occurring?
A: Studies are necessary to prove that uncontrolled cell growth is not occurring. Also the level of purity must be determined for acceptable level of risk.
Q: Will these current regulations change over time?
A: Yes, absolutely. They will evolve as new information is revealed and laboratory techniques are improved.