National Ethical Standards
- Part one
- Part two
- 1. Scope of the Standards
- 2. Ethical principles
- 3. Research and Māori
- 4. Research and Pacific peoples
- 5. Disability research
- 6. Ethical management of vulnerability
- 7. Informed consent
- 8. Research benefits and harms
- 9. Research development and design
- 10. Ethical features of studies
- 11. Research conduct
- 12. Health data
- 13. Health data and new technologies
- 14. Human tissue
- 15. Biobanks
- 16. Research with stem cells and reprogrammed cells
- 17. Compensation for injury in commercially sponsored intervention studies
- 18. Quality improvement
- Part three
16. Research with stem cells and reprogrammed cells
Adding to the general considerations that apply to the ethics of research presented in these Standards, and specifically to research with human tissue, this chapter focuses on research with stem cells. Human stem cells are characterised by their capacity for self-renewal and their ability to differentiate into different types of cells under the right conditions. Stem cells can be divided into a number of broad categories, each of which have different ethical considerations.
These categories include:
- tissue-derived stem cells
- embryonic stem cells, and
- induced pluripotent stem cells.
Stem cell research has two broad arms: 1) clinical interventions whereby stem cells are administered to patients, and 2) scientific investigations whereby the biology of stem cells is studied in various ways but the cells are not administered to patients. These Standards recognise that the risks associated with the two arms are very different. They set out special considerations about collecting and using stem cells, a stepped-level of informed consent (which distinguishes research and treatment), and health and disability ethics committee approval for establishing tissue banks for the storage of stem cells. They also distinguish the future use of stem cells from protocol-specific research, especially the requirements for separate consent.
Research with stem cells, stem cell lines and foetal tissue are subject to specific legislation and national guidelines, including:
- Human Tissue Act 2008 – in terms of the collecting, storing and disposing of stem cells (although section 7 of the Act states that cell lines are not tissue, section 74 provides for regulations for their use in research)
- He Tangata Kei Tua: Guidelines for Biobanking with Māori (Hudson et al 2016a)
- Te Ara Tika: Guidelines for Māori Research Ethics (Hudson et al 2010)
- Guidelines for Using Cells from Established Human Embryonic Stem Cell Lines for Research (Ministry of Health 2006)
- the International Society for Stem Cell Research’s Guidelines for Stem Cell Research and Clinical Translation (ISSCR 2016).
Use of stem cells in scientific non-clinical research
The risks involved in the use of stem cells for non-clinical research are much lower than the risks for the use of stem cells in clinical research.
16.1 Researchers should seek approval from an ethics committee for all research involving the isolation and derivation of stem cells or cells that will be used for reprogramming, and undertake such research only following written informed consent.
16.2 In some exceptional situations, consent for such research may be impossible or impracticable to obtain. In this case, researchers may only conduct the research after an ethics committee has considered and approved it.
Use of stem cells in clinical research
16.3 All research involving the clinical application of stem cells or reprogrammed cells must be subject to prospective ethical review, approval and ongoing monitoring by an independent ethics committee and registration with a recognised clinical trials registry. Such research must also be monitored by a data safety monitoring committee.
16.4 All researchers intending to conduct research involving the clinical application of stem cells or reprogrammed cells must demonstrate an appropriate level of quality control in the production of the cells, including in terms of the purity of the cells and the absence of oncogenic potential.
16.5 Researchers creating a stem cell line or reprogrammed cell line for clinical use must obtain informed consent for the future use of the tissue separately from informed consent for clinical treatment.
16.6 Research involving the development of stem cells or reprogrammed cells for clinical use must be scientifically justified. It must be conducted (and peer reviewed) by individuals with appropriate expertise.
16.7 For products derived from totipotent or pluripotent stem cells, researchers must plan to minimise the persistence of any remaining undifferentiated cells, and demonstrate that these cells do not result in tumours in long-term animal studies, where appropriate (ISSCR 2016).
16.8 The appropriate therapeutic committee (typically SCOTT or GTAC) must review preclinical data and the trial protocols of research involving stem cells or reprogrammed cells.
16.9 Before any research employing stem cells or reprogrammed cells for therapeutic use begins, researchers must establish the specific risks and benefits associated with the particular type of cell research. In addition, they must adopt practices that address long-term risks associated with the procedures.
16.10 Where applicable, an intervention employing stem cells or reprogrammed cells must aim at being clinically competitive with or superior to existing therapies, or meet a unique therapeutic demand, or provide unique therapeutic outcomes.
16.11 Where applicable, researchers should recruit participants in clinical stem cell or reprogrammed cell research from populations that can benefit from the results of the research.
16.12 Early-phase clinical trials in which there will be an intervention involving stem cells or reprogrammed cells may enrol research participants who have run out of standard treatment options.
16.13 Researchers must not require participants to pay to participate in studies about stem cells.
16.14 Where research proves that stem cells or their derivatives have therapeutic benefit, researchers should disseminate this information as widely as possible.
16.15 Research employing stem cells or reprogrammed cells for clinical or therapeutic use may be associated with specific risks (such as cell contamination). Researchers must consider these risks in advance of their research, and address them in their protocols.
16.16 As stem cell or reprogrammed cell research may use identifiable human material or data (such as data contained in biobanks or similar repositories), researchers must seek informed consent for collecting, storing and reusing it. In some exceptional situations, consent for such research may be impossible or impracticable to obtain (e.g. in the case of cells obtained from a cell repository such as the American Type Culture Collection). In such situations, researchers may only conduct the research after a research ethics committee has considered and approved it.
16.17 Consent procedures for stem cell-based or reprogrammed cell-based interventions should promote a full understanding of any possible benefits or therapeutic aspects of participating, so that potential research participants do not overestimate or misunderstand them.
16.18 Researchers should distinguish the protocol-specific intentions of their research from any future use of the material or data, and obtain separate consent for each of these activities.
16.19 When a clinical trial involves human research participants with less advanced disease, or when researchers anticipate using invasive delivery approaches (for example, the intramyocardial method) for stem cells or reprogrammed cells, researchers must follow stringent design and reporting standards.
16.20 All stem cell research must only be conducted by people with appropriate expertise and/or training. Relevant expertise includes previous experience with tissue culture techniques, embryo culture and stem-cell derivation in animal systems, and competence in the culture and maintenance of cell lines.
Human embryos and embryonic stem cells
In 2006, the Ministry of Health released Guidelines for Using Cells from Established Human Embryonic Stem Cell Lines for Research (Ministry of Health 2006). These guidelines provide health and disability ethics committees with an ethical framework for assessing applications to use established human embryonic stem cell (hESC) lines.
The International Society for Stem Cell Research’s Guidelines for Stem Cell Research and Clinical Translation (ISSCR 2016) holds that scientific research on pre-implantation stage human embryos (especially research in human development, genetic and chromosomal disorders, reproduction and potential disease therapies) is ethically permissible when performed under rigorous scientific and ethical oversight.
16.21 In the New Zealand context, the Human Assisted Reproductive Technology Act 2004 provides specific legislation relating to research on non-viable embryos up to 14 days. It prohibits:
- incorporating human totipotent or pluripotent cells into animal hosts to achieve chimerism
- modifying the nuclear genome of human embryos for the purpose of human reproduction (this includes mitochondrial replacement therapy)
- culturing in vitro any embryo-like cellular structure with human organismal potential, regardless of derivation method, beyond 14 days.
Embryonic stem cells
Under the Ministry of Health’s 2006 guidelines, researchers are able to use cells from established hESC lines with ethical approval.
Once established, hESCs are not embryos, and their use does not require the same level or type of regulation.
16.22 When considering research projects with hESCs, researchers must assess their research goals within an ethical framework to ensure that proposed research with human embryonic stem cells proceeds in a transparent and responsible manner. Their study proposal should discuss alternative methods (if available), and provide a rationale for using the requested human materials. This rationale must include a justification for the derivation or use of hESC, for the proposed methodology and for performing the experiments in a human rather than animal model system.
16.23 All research involving hESCs must comply with relevant documents and legislation, namely, the Guidelines for Using Cells from Established Human Embryonic Stem Cell Lines for Research (Ministry of Health 2006), the Human Tissue Act 2008 and the relevant guidelines of the Advisory Committee on Assisted Reproductive Technology.
16.24 The genetic modification or import of genetically modified human cells, tissues, gametes or embryos grown outside of the human body requires an approval from ERMA. Where researchers plan to import a cell line into New Zealand for the purpose of using established hESCs involving genetic modification must receive approval from ERMA, in addition to any other approvals required, before the cell line can be imported into New Zealand.
16.25 Researchers wanting to use New Zealand-derived embryos to create genetically modified hESC lines need to seek approval from both ECART and ERMA. If these hESC lines are to be used in clinical research or therapy (non-reproductive), the researcher also needs to seek approval from a health and disability ethics committee.
16.26 All research that involves totipotent or pluripotent cells derived from the inner cell mass of pre-implantation stages of human development, human embryos or embryo-derived cells is subject to ethical review, approval and ongoing monitoring by ECART. It must address the uniquely sensitive elements of hESC research.