Frequently Asked Questions About Stem Cells

For maximum efficiency of the treatment by using stem cells, the “cell therapy product” must pass the certification in the pharmaceutical procedure, the immunology procedure, or the product metabolic procedure so that the safe product could be obtained for therapeutic use, the prevention and the diagnosis of disease in human. In addition, cell therapy must have qualified long-term safety examination such as the immunogenicity, the immunosuppression and may also include the malignant transformation, in order to ensure that the use of stem cells is safe.

Therefore, the Food and Drug Administration (FDA) has issued the Announcement of the Food and Drug Administration on the registration of the Advanced Therapy Medical Product (ATMP), to control, monitor, and consider the registration of the in Thailand. According to the international standard, the specifications related to the biological properties of cell therapy products, the verification of donor, product, and recipient, or the verification of the product-recipient for autologous product, shall conform to the international standard and related laws.

Good Manufacturing Practice or GMP is the very important standard that identifies that such product or medicine already passes the strict standard control and can be traced back even in the slightest detail, in order to confirm and certify the safe use.

This is the manufacturing of stem cells – it is necessary to have strict standard control in order to obtain efficient and safe cell also it must be legal for use in treatment. Bringing stem cells, which are cultured in the laboratory where there is no standard or quality control may increase the risk of infection to patient caused by the cells of no quality, as reported in the United States that there was a patient receiving stem cells that were not standard controlled, to treat his cornea and finally such patient became blind (AE Kuriyan et al., 2017).

Furthermore, the treatment in form of stem cell tourism where there is no process of checking for the source of stem cell also increases the risk in the treatment, for example, the multiple myeloma disease (AL Berkowitz et al., 2016) was found from the use of stem cells without quality control to treat patient who had backache.

Stem cell therapy products both autologous stem cells that are collected from a person and then give back to treat only that person, and autologous stem cells that are collected from other persons are manufactured according to the regulations of FDA on the guidelines for Advanced Therapy Medicinal Product (ATMP) registration. The manufacturer has to go through the registration of drug formulation for such product, covering product development, manufacturing and quality control.

For the process of storing and separating stem cells from blood, SCL laboratory has used a semi-automatic process that allows to control potential risks in many points. If any potential risk is found, the separation process will be optimized promptly. In comparison with the process with reduction of human costs by adopting an automatic machine–this type of machine can only resolve the final separation process, which may affect the quality of stem cells separated prior to storage.

The mesenchymal stem cell production process of SCL laboratory has been granted permission to operate according to the above requirements. SCL is the only company in Thailand that has been legally licensed and has been certified ISO 9001: 2015 stem cell manufacturing , as well as adopting the world-class international standard in identifying each type of cell to be coded (ISBT 128 standards), complying with the Good Manufacturing Practice (GMP), Pharmaceutical Inspection Convention, Pharmaceutical Inspection Co- Operation Scheme (PIC/S), and Standard Operating Procedure (SOP) . Moreover, stem cell characteristics are investigated according to the ISCT requirements (International Society forCellular Therapy) to ensure that the stem cells produced from SCL laboratory are legally valid to produce the best and safest stem cells, in order to be ready for the future application.

The manufacturing and the quality control would affect the quality of the cell therapy product or the manufactured stem cells. The procedures are range from the selection of raw materials to be used in the production, separation, expansion and storage of stem cells. The raw materials are diverse and different, for example, the media for culturing cells are different under the quality analysis including the media for research only, the cell specific media, as well as the GMP-grade media or Clinical grade. The supplement from the media would directly affect the cell properties, the cell efficiency and the “stemness of stem cell”. Besides, it might cause contamination that comes from the foreign substances of raw materials and materials that are low quality or are not suitable for the right work.

SCL laboratory has realized the risk that might happen in the procedure, the quality and the cells of the clients of SCL laboratory. Therefore, we selected raw materials and materials concerned with the whole process of manufacturing to be clinical grade, which is of the best quality, with low risk of contamination, and passes the good manufacturing practice (GMP) process to prevent mistakes that might happen in culturing cells, even though, this might increase the cost of the culturing and the storage process.

The modern medicine called the Regenerative Medicine is a new branch of medicine that focuses on the replacement, repair, and regeneration of cells, tissues, or the degenerative human organs, by using new technology with the use of advanced therapy medicinal products (ATMPs).

The medicinal products that consist of living cells on part of the cell therapy medicinal products with cells as the elements for an efficient in treating many diseases. In addition, the ATMPs also considered use of gene therapy medicinal product, the use of tissue engineered product and the combined ATMP products.

The Cell Therapy products are different depending on the source of cells, type of cells, and the complexity and variety of products, that may include the self-renewing stem cell, more committed progenitor cell, and terminally differentiated cell, to focus on the effective treatment for health, structure of the body, or functioning of the human body.

Stem cells are undifferentiated cells that can differentiate into various types of specific cells and proliferate indefinitely to produce more of the same stem cell. Based on their source of origin, stem cells can be categorized into the following types:

Type 1 : Embryonic Stem Cells (ESCs) are pluripotent stem cells derived from the inner cell mass of blastocyst, an early-stage pre-implantation embryo. However, using this type of stem cells has been suspended because the isolation of ESCs is unethical and importantly, the control of their actual use is not well regulation.

Type 2: Adult or Somatic Stem Cells are found throughout the body and can be isolated from various parts of the body such as bone marrow, adipose tissue, placenta, and umbilical cord. Stem cells are the origin of cells in the body systems, including organs, for example, hepatic stem cells which are used to promote the repair of abnormal liver function; muscle stem cells that help to restore the functioning of the degenerative muscular system. The important stem cells in this group are Hematopoietic Stem Cell (HSCs) and Mesenchymal Stem Cell (MSC).

Hematopoietic stem cells (HSCs) are blood element stem cells that replacing the damaged or expired blood cells and elements. They can differentiate to be red blood cells which carry oxygen around the body, white blood cells that help fight foreign bodies or pathogens and platelets that help stop bleeding when a wound occurs. Sources of HSCs are bone marrow, peripheral blood, and Umbilical cord blood

The flowing diseases can be treated with hematopoietic stem cells (HSCs):

1. Diseases related to disorders of the bone marrow
2. Blood cancers such as leukemia or other cancers requiring chemotherapy
3. Congenital immunodeficiency
4. Platelet disorders
5. Red cell disorder such as Aplasia
6. Anemia from various causes and needed regular blood transfusion.
7. Thalassemia diseases
8. Inherited metabolic disorders such as Osteopetrosis

Advantages of collecting Hematopoietic Stem Cells (HSCs) from umbilical cord blood

1. Can be collected easily and takes no more than 5 minutes, no pain or risk to the mother and baby.
2. Can be immediately used to treat the child who is the owner of the stem cells.
3. A high comparability for use to the donor’s family members of or other persons related by blood
4. HSCs from cord blood has a higher quantity and efficiency than bone marrow.
5. Lower risk of contamination.

There is the expectation of using stem cells in the treatment of various diseases. In addition to blood diseases, there are continually studies on the use of stem cells and the results of the studies are promising in many diseases, including brain and nervous system disorders: Parkinson and Alzheimer; bone diseases: osteoarthritis and rheumatoid arthritis, and vascular disease caused by acute inflammation: spinal cord injury and stroke, as well as other common diseases such as heart disease and diabetes.

The culturing of stem cells to be standardized and safe requires the controlling and the monitoring of laboratory—the temperature, pressure, incoming and outgoing wind must be managed, and the particles in the air must be controlled by using High Efficiency Particulate HEPA Filter to filter small particles so that they would not enter into the laboratory. T has been categorization of laboratory under the quantity of particles found in the air in the unit of particles/ m 3 of air, where for the clean room Class 100 (ISO 5), there would be particles with the size of larger than 0.5 microns but not exceeding 100 particles/ m 3 of air. Therefore, in culturing stem cells, it is vital to control the conditions of room to be clean under the requirement in order to obtain the good and safety cell products. Using Class100 clean room could help establish the standard of manufacturing the stem cells to be equal to the international standard.

AABB or the American Association of Blood Bank is an association established for governing and setting standards for blood banks for 50 states in the United of America. Later, it becomes to be an international association that brings together scholars who are expert on medical science, all examination techniques in blood bank, and blood disease treatment, and sets the standards for quality inspection and accreditation.

In addition, there are other international organizations that play a role in blood service- -including World Health Organization (WHO), International Federation of Red Cross and Red Crescent Societies – IFRC/RC), International Society of Blood Transfusion – ISBT) , International Federation of Blood Donor Organizations – IFBDO/ FIODS), Council of Europe – COE, and International Plasma Fractionation Association – IPFA).

For the blood banks in Thailand, the National Blood Center, Thai Red Cross Society, has collaborated with Ministry of Public Health and the University Bureau as the main organization for building cooperation and determining the National Blood Policy to be the master plan and guideline. For the blood service in 1989. The master plan and guideline are updated in 1995 and 2010, and become to be the version used today. Many standard systems are set to cover a wide variety of tasks and to ensure that they can be performed to achieve the goals and to meet the guidelines of the World Health Organization. It has been certified according to ISO 9001 in 2000, and ISO 15189 and ISO 15190 for medical laboratory in 2014, and recently GMP certification for the manufacturing sector in 2017.

Due to an increase in stem cell operations and development in Thailand today, National Blood Center – which is responsible for and is part of this development nationally–has therefore planned and implemented the system in accordance with World Marrow Donor Association (WMDA) standard, which is the international Standards for Unrelated Hematopoietic Stem Cell Donor Registries, for providing allogeneic stem cell donation service, with the schedule for completion in 2020. Moreover, National Blood Center still commits to raise the standards to be strengthen and to cover all departments and responsible missions.

For SCL laboratory, blood stem cell separation has been performed in accordance with the requirements of the National Blood Center, the Thai Red Cross Society in order to conform with the World Health Organization guidelines strictly. The quality control system of production standard (Good Manufacturing Practice: GMP) , the inspection of product quality (Qualification & Safety Control) for use of cell therapy will be based on the requirements of Advanced Therapy Medicinal Products (ATMPs), as well as characterization of the cell product before use.

In addition, for mesenchymal stem cell (MSCs), there is a preliminary agreement for product verification by The International Society for Cellular Therapy (ISCT). It can be seen that all of these requirements are the standard of validation for obtaining the good quality and safe hematopoietic stem cells according to the standard of National Blood Center, the Thai Red Cross Society, which meet the goals and guidelines of World Health Organization.

We have a team of scientists specializing in stem cells. They supervise stem cell samples from collection, separation, culture, and storage. With our work experiences in stem cells for more than 10 years , you can be assured that the need of our customers or any potential problems will be explained precisely and prompt for customer’s decision about stem cell collection. Moreover, we have a team of doctors who have experience in the use of cell therapy stationed at our office , which they can provide advice our customers promptly about treatment possibility or opportunity of using stem cells correctly for the best clinical benefits.