NIH Guidelines for Human Stem Cell Research (Proposed Changes) & Internal NIH Steering Committee on Human-Animal Chimera Research (Proposed Scope)

The Policy

What it does

Expands restrictions surrounding human stem cell research in animals and establishes a new NIH steering committee to advise internal agency stakeholders on chimera research funding.


Stem cell research has the potential to inform many new therapeutics to treat disease, however, the acquisition of stem cells and the applications of this technology raise ethical concerns. Because of these ethical concerns, funding of certain stem cell research proposals through the National Institutes of Health (NIH) is restricted. This proposal (noticed via the Federal Register, 81 FR 51921, on August 5, 2016) includes a request for public comment on 1) pending changes to the NIH Guidelines for Human Stem Cell Research and on 2) the duties of an NIH created steering committee, established to provide input to NIH institutes and centers on human/animal stem cell research proposals submitted for funding consideration.

1) Currently, the NIH Guidelines for Human Stem Cell Research:

  • Bans the introduction of human embryonic stem cells (hESCs) or induced human pluripotent stem cells (iPSCs) into non-human primate animal embryos at the blastocyst stage, an early stage of embryonic development; and
  • Prohibits research that involves breeding of animals where introduced hESCs and iPSCs could contribute to the germ line (i.e. be able to be passed onto offspring).

The amended regulation would:

  • Expand the existing ban to restrict introduction of stem cells into non-human primate animal embryos, to include the preblastocyst stage.
  • Expand the current prohibition to include restricting the breeding of animals using any human cells that could contribute to the germ line.

2) A new NIH steering committee will review research proposals related to human/animal stem cell research and provide input to appropriate NIH centers and insitutes making funding decisions. This input will be in addition to the normal peer-review process undergone by all NIH research proposals. The committee will address:

  • The type and characteristics of cells being introduced;
  • The characteristics of the animal set to receive the cells;
  • Other information about the proposed research that could affect the receiving animal’s cognition, physical appearance or behavior;
  • Details about monitoring of the receiving animal after stem cell introduction; and
  • The order of the proposed studies and data required from a first experiment before continuing with a follow-up study or experiment.

The NIH proposes to define steering committee responsibilities to include oversight of research proposals that include:

  • Introduction of iPSCs into non-human vertebrate animals up through the end of the gastrulation stage, an early stage of embryonic development that falls after the blastocyst stage, or
  • Post gastrulation stage introduction of any human cells into non-human mammals that have the potential to alter the brain of the receiving animal.


The Science

Science Synopsis

Stem cells are unspecialized cells capable of forming, through cell division, either another stem cell, or a cell of a specific organ or tissue. Stem cells are responsible for the original creation of the body’s different organs and tissues during development, and also serve to regenerate and repair tissues in adults. Because of the regenerative properties of these cells, they have great potential in human health and disease treatment. Stem cells studied in the laboratory are generally one of three types:

  • Embryonic stem cells: Stem cells derived from embryos. These embryos usually come from eggs that are fertilized in a laboratory. These cells can differentiate into any cell of the body.
  • Adult (somatic) stem cells: Undifferentiated cells within a specialized organ or tissue. These cells usually function to repair or regenerate the organ in which they are found.
  • Induced pluripotent stem cells: Adult cells that have been reprogrammed to act like embryonic stem cells, making them capable of dividing into any cell type.

New avenues of stem cell research involve the introduction of induced human pluripotent stem cells into animal embryos. Animals containing human cells are called ‘chimeras’. This type of research could allow for the modeling of organ function and human disease in animals. It also has the potential for growing human organs in animals for transplantation. Ethical concerns arise from this type of research as introduction of foreign cells into the animal could potentially affect other organ systems of the receiving animal, including the nervous system and the brain.

The timing of stem cell introduction into animal embryos is highly restricted. The process of cell division and differentiation that occurs after fertilization of an egg is called embryogenesis. Fertilization of an egg results in a single fused cell called a zygote. The first ten days of development is known as the germinal stage. These cells divide and compact, eventually forming a hollow ball of cells known as a blastocyst. The blastocyst has two layers: tightly compacted outer cells, called trophoblasts, and an inner cell mass, called embryoblasts. The inner cell mass consists of pluripotent cells. Following the blastocyst stage, these pluripotent cells begin to differentiate to form the germ layers of the body during gastrulation. There are three germ layers that form during gastrulation:

  • Ectoderm: Develops into the skin and nervous system;
  • Mesoderm: Develops into muscle, cartilage, blood, bone and connective tissue; and
  • Endoderm: Develops into the digestive and respiratory systems.

Introduction of stem cells during gastrulation would allow the cells to divide and differentiate during gastrulation, effectively integrating into the receiving animal. Following gastrulation, organogenesis occurs during which time cells of the germ layers differentiate to form specific organs and tissues.

Certain cells are set aside during initial embryonic cleavage that will form gametes (eggs or sperm). These cells can be passed on to offspring and therefore would contribute to the germ line.

The Debate