11/5/15

To:

From:

Subject:

Office of Science Policy, Office of the Director National Institutes of Health (NIH)
California Institute for Regenerative Medicine (CIRM)
CIRM Policy to Ensure the Responsible Conduct of Research with Animals
Containing Human Cells

Introduction:

The NHI Office of Science Policy is conducting a workshop to consider how to ensure the
responsible conduct of research with animals containing human cells. The California Institute
for Regenerative Medicine (CIRM) is authorized, under the California Stem Cell Research and
Cures Act, to support research involving human stem cells. Institute-sponsored research
includes studies involving the transplantation of human cells into vertebrate animals. These
studies are conducted in accordance with CIRM regulations, which include a system of review
and oversight designed to ensure the responsible conduct of research.1

Policy Summary:

CIRM requires review and approval, by a stem cell research oversight committee (SCRO), of
proposed studies involving the transplantation of human pluripotent stem cells into non-human
animals or the introduction of human neural progenitor cells into the brain of non-human
animals at any state of embryonic, fetal or postnatal development. The SCRO committee
evaluates the scientific rationale for the research and the probable pattern and effects of
differentiation and integration of the human cells into the animal.

Policy Impact:

CIRM maintains ongoing initiatives to evaluate and improve the Institutes programs and
policies the Evaluation Initiative (2006) and the Compliance Program (2007). These programs
include workshops, site visits and technical assistance to support oversight and compliance
activities. Site visits are designed to review grantee compliance with stem cell research review
and oversight requirements. Based on these site visits, CIRM determined the following:

All major CIRM grantees have a designated SCRO committee.

SCRO committees have established written procedures and policies consistent with
CIRM regulatory requirements.


1
https://www.cirm.ca.gov/our-funding/cirm-stem-cell-grant-regulations

CIRM Policy to Ensure the Responsible Conduct of Research with Animals Containing Human Cells

The designated SCRO committees membership includes a non-scientist member and a

patient advocate.

Site visits include in-depth review of selected grants. Documentation associated with the
specific grant award (SCRO meeting minutes, approval letters, and correspondence) is reviewed
to verify the institution is adhering to CIRM requirements and its internal SCRO procedures and
policies. During site-visits, CIRM has reviewed twelve protocols at seven different institutions
where stem cells or neural progenitor cells were introduced into vertebrate animals. CIRM
found that all protocols were reviewed and approved by a SCRO committee consistent with
CIRM requirements.

Operational Impact:

By interacting with grantees at workshops, during site visits and through the provision of
technical assistance, CIRM has gained insight into the general approaches to stem cell research
oversight. Major CIRM grantees stem cell research oversight programs include some or all of
the following components:

Staff training and continuing education focused on stem cell research ethics.
Standard SCRO committee application procedures to clearly identify materials and
methods to identify the level of review required (e.g., administrative vs. full committee).
Written operating procedures for SCRO committee staff and members.
Feedback mechanisms designed to provide periodic updates on protocols and inform
annual renewals.


Research Experience:

CIRM has funded, in whole or part, protocols with the aim of introducing human cells to
animals. These studies include blastocyst complementation protocols in animal models
designed to advance the development of therapies. In preparation for this workshop, CIRM
conferred with institutional officials responsible for research oversight. Institutional officials at
one institution described the processes employed for the review and oversight of a blastocyst
complementation protocol. For the protocol in question, the following actions were taken:

The SCRO committee convened for a full protocol review as required by CIRM policy and
the institutional SOPs.
The review included seeking external expert advice and discussion sessions with the
SCRO committee and the investigator focusing on the current practices and ethical
issues surrounding this type of research, and providing input as to how the protocol
could be revised (for example, limiting time of gestation) while still addressing critical
research questions.

CIRM Policy to Ensure the Responsible Conduct of Research with Animals Containing Human Cells

After initial deliberation, the SCRO committee further consulted with the Vice
Chancellor for Research to address broader questions of perspective and perception.
Based on SCRO committee deliberations and consultation with the Vice Chancellor for
Research, a revised protocol was approved with requests for periodic status reports.

Policy Review

CIRM maintains a standing advisory body, the Scientific and Medical Accountability
Standards Working Group2, comprised of external experts to recommend to the Institutes
governing board standards for research oversight. The Standards Working Group recently
reviewed CIRMs policies governing the transplantation of human cell to animals. This
review included consideration of the transplantation of neural progenitor cells to the brains
of pre-natal animals. The working group affirmed CIRM existing policy supporting such
studies provided continued review and oversight by a SCRO committee.

2
https://www.cirm.ca.gov/sites/default/files/files/board_meetings/140924_Standards_Working_Group_List SWG.pdf