Recently updated guidelines from the International Society for Stem Cell Research address many controversial, rapidly evolving areas.1

The 2021 guidelines offer specific recommendations for embryo research, stem cell embryo models, organoids, chimeras, germline genome editing, and mitochondrial replacement techniques. Public support for controversial research is an overarching goal. “If controversial areas of scientific biomedical research are not trusted by the public, then the benefits of this research are diminished,” says Amander Clark, PhD, guidelines co-author and chair of the UCLA Department of Molecular, Cell, and Developmental Biology.

Ultimately, science aims to serve societal interests. “The ethical duty of beneficence extends beyond the purview of the physician. It also includes biomedical researchers hoping to make a positive impact on future developments in biomedicine,” says Insoo Hyun, PhD, guidelines co-author and faculty member at the Harvard Medical School Center for Bioethics.

For preclinical research, clinical trials, and approval processes, it is important there are “no loopholes or gray areas or gaps. This is something that governments need to confront and address,” says Leigh Turner, PhD, guidelines co-author and an associate professor at the University of Minnesota Center for Bioethics.

Stem cell research requires careful oversight to find out if it is safe and efficacious. “The burden is on researchers to generate that evidence, rather than just assume it,” Turner says.

The 2021 guidelines include a new category: research that is not permitted now, but might be one day. “The 14-day rule is a good example of this,” Clark offers. For jurisdictions that permit research with human embryos, the international consensus is embryos should not be cultured for longer than 14 days from the point of fertilization or formation of the primitive streak, whichever occurs first. This is known as the 14-day rule.

“In most jurisdictions, even those that are permissive to embryo culture rules, a scientific and ethical oversight process monitors experiments to ensure that the 14-day rule is observed,” Clark says.

However, the formation of the primitive streak and the patterning of the embryo, which occur on and after the 14th day, are critical for embryo survival as well as healthy embryo and fetal development during pregnancy. “Therefore, studying these events using embryos cultured in vitro under appropriate regulatory oversight could help scientists understand and, therefore, develop treatments for devastating childhood disorders that begin before birth,” Clark says. Examples could include neural tube defects, heart defects, or neurological disorders.

The gestation and subsequent live birth of animal host embryos containing human stem cells (i.e., nonhuman chimeric embryos) is another example of research no one is actively pursuing, but might one day go forward. “Such research must be aimed at an important scientific question that is of clinical relevance for understanding human disease, and it must be carried out using the least complex animal embryo species,” Hyun says.

Frequent examination of the chimeric embryo’s developmental progress must be conducted along the way at defined points so there are no surprises when the chimeric animal is born. “This ensures that the human contribution is localized to the specific tissue type of clinical interest,” Hyun explains.

The guidance also addresses the ongoing issue of businesses marketing stem cell products. These continue to proliferate across the United States. One can find these products in every state, with hot spots including Texas, Florida, and California.2 This has been the case for years. “What’s changed is the recognition of the extent that this is a serious problem for patient safety and public health,” Turner says.3,4

To better regulate stem cell clinics, the FDA sent warning letters to hundreds of businesses, warning that they may be in violation of federal law, and sought permanent injunctions against several organizations.5,6 “But while the FDA was taking action against some businesses, many more saw a commercial opportunity and set up shop,” Turner notes.

Today, the FDA is confronted with a vastly bigger marketplace, with finite resources. “There’s a limit to the number of businesses that can be dragged into court,” Turner observes. “Some might decide to play the odds — and, in the meantime, can make a pile of money.” 

REFERENCES

  1. Lovell-Badge R, Anthony E, Barker RA, et al. ISSCR guidelines for stem cell research and clinical translation: The 2021 update. Stem Cell Reports 2021;16:1398-1408.
  2. Turner L. The US direct-to-consumer marketplace for autologous stem cell interventions. Perspect Biol Med 2018;61:7-24.
  3. Bauer G, Elsallab M, Abou-El-Enein M. Concise review: A comprehensive analysis of reported adverse events in patients receiving unproven stem cell-based interventions. Stem Cells Transl Med 2018;7:676-685.
  4. Lomax GP, Torres A, Millan MT. Regulated, reliable, and reputable: Protect patients with uniform standards for stem cell treatments. Stem Cells Transl Med 2020;9:547-553.
  5. The Pew Charitable Trusts. Harms linked to unapproved stem cell interventions highlight need for greater FDA enforcement. Issue Brief. June 1, 2021.
  6. U.S. Food & Drug Administration. FDA extends enforcement discretion policy for certain regenerative medicine products. July 20, 2020.