Research Involving Human Stem Cells

Research Involving Human Stem Cells

Guidance for Arizona State University

Revised June 7, 2010

Purpose

The purpose of this guidance document is to provide updated information to investigators and the University community to assure that all research at ASU involving human adult or embryonic stem cells is conducted in a responsible and ethical manner and complies with all federal and state laws, ethical guidelines and University policies.

Federal and State Policies and Legislation

Executive Order (EO) 13505: Removing Barriers to Responsible Scientific Research Involving Human Stem Cells, Federal Register Vol. 74, 46; March 11, 2009.

National Institutes of Health (NIH) Guidelines for Human Stem Cell Research (Guidelines),

July 7, 2009.

The Arizona Revised Statutes (“A.R.S.”) contain the following prohibitions:

·  A.R.S. §§ 36-2302 and 36-2303 prohibit the use of a human fetus or embryo (living or dead) resulting from an induced abortion for research purposes or any parts, organs or fluids of any such embryo or fetus without regard to the funding source.

·  A.R.S. § 35-196.04 prohibits the use of public monies for human cloning research.

·  A.R.S. §§ 36-2311 to 36-2313 prohibit: (i) the purchase or sale or the offer to purchase or sell an in vitro human embryo (but does not prohibit payment to a physician by a patient or on a patient’s behalf for otherwise lawful treatment of infertility); (ii) the intentional or knowing creation of or attempt to create an in vitro human embryo by any means other than fertilization of a human egg by a human sperm; (iii) the intentional or knowing creation of or attempt to create a human-animal hybrid; (iv) the intentional or knowing transfer of or attempt to transfer a human embryo into a nonhuman womb; (v) the intentional or knowing transfer of or attempt to transfer a nonhuman embryo into a human womb; (vi) the transportation or receipt for any purpose of a human-animal hybrid; and (vii) the intentional or knowing engagement in destructive human embryonic stem cell research. The statutes do not prohibit research that involves the use of transgenic animal models containing human genes and xenotransplantation of human organs, tissues or cells into recipient animals other than animal embryos as long as such activity does not violate the prohibitions of the statutes.

Definitions

Adult (or somatic) stem cell - Cell that can renew itself and differentiate (with certain limitations) to give rise to all the specialized cell types of the tissue from which it originated.

Destructive Human Embryonic Stem Cell Research – Any research that involves the disaggregation of any human embryo for the purpose of creating human pluripotent stem cells or human pluripotent stem cell lines.

Human Animal Hybrid – Means any of the following: 1) Human embryo into which a nonhuman cell or cells, or any component part of a nonhuman cell or cells have been introduced, 2) Hybrid human-animal embryo produced by fertilizing a human egg with a nonhuman sperm, 3) Hybrid human-animal a embryo produced by fertilizing a nonhuman egg with a humans sperm, 4) Embryo produced by introducing a non-human nuclease into a human egg, 5) Embryo produced by introducing a human nucleus into a nonhuman egg, 6) Embryo containing at least haploid sets of chromosomes from both a human and a nonhuman life form, 7) Nonhuman life form engineered so that human gametes develop within the body of a nonhuman life form, or 8) Nonhuman life form engineered so that it contains a human brain or a brain derived wholly or predominantly from human neural tissues.

Human Cloning - Human somatic cell nuclear transfer which means, more specifically, human asexual reproduction that is accomplished by introducing the genetic material from one or more human somatic cells into a fertilized or unfertilized oocyte whose nuclear material has been removed or inactivated so as to produce an organism, at any stage of development, that is genetically virtually identical to an existing or previously existing human organism.

Human Embryo - A set of rapidly dividing cells in the early stages of development into a human being, usually defined as extending from the time of implantation in the uterus through the end of the first eight weeks (56 Days) after fertilization of a human egg.

Human Embryonic Stem Cells - Cells that are self-replicating derived from human embryos and are capable of developing into cells and tissues of the three primary germ layers. Although human embryonic stem cells are derived from embryos, such stem cells are not themselves embryos.

Human Subject - A living individual about whom an investigator conducting research obtains (1) data through intervention or interaction with the individual, or (2) identifiable private information.

Human Somatic Cell Nuclear Transfer –Human asexual reproduction that is accomplished by introducing the genetic material from one or more human somatic cells into a fertilized or unfertilized oocyte whose nuclear material has been removed or inactivated so as to produce an organism, at any stage of development, that is genetically virtually identical to an existing or previously existing human organism.

In Vitro – outside the human body

Induced pluripotent stem cells (iPSCs) - Adult cells that have been genetically reprogrammed to an embryonic stem cell-like state by being forced to express genes and factors important for maintaining the defining properties of embryonic stem cells.

Institutional Biosafety Committee - University committee responsible for reviewing research involving use of recombinant DNA molecules, infectious and select agents.

Institutional Review Board - University committee established to protect the rights and welfare of human subjects recruited to participate in bioscience, social behavioral, or clinical research investigations.

Public Monies - Tax monies of the State of Arizona or any political subdivision of the State of Arizona, federal monies passing through the state treasury of Arizona or the treasury of any political subdivision of the State of Arizona or any other public monies (money belonging to, received or held by state, county, district, city or town officers in their official capacity.

Purchase of Sell – includes an exchange of cash, an in-kind payment or any other valuable financial or nonfinancial consideration. Does not include payment or costs related to donation of a human embryo for the purpose of implantation in the body of a woman.

Research - Activity undertaken to develop or contribute to generalizable (scholarly) knowledge or to devise new applications for such knowledge. Research activities include, but are not limited to, clinical trials, pilot testing, research development, product testing, evaluation of programs and services, fieldwork and the use or care of animals for research.

Somatic Stem Cells - Non-embryonic stem cells that are not derived from gametes (egg or sperm cells).

Stem cells - Cells with the ability to divide for indefinite periods of time in culture and to give rise to specialized cells.

NIH Guidelines

On March 9, 2009, President Obama signed an Executive Order repealing some of the limitations placed on federal funding for research involving human embryonic stem cells (hESCs) and certain uses of induced pluripotent stem cells. The Executive Order does not alter the prohibition against the use of federal funding for research involving the creation or destruction of embryos for research purposes. However, the Executive Order changes the way NIH can support and conduct research involving hESCs. Pursuant to the Executive Order, the NIH issued the Guidelines on July 7, 2009. Additional information is available on the NIH Stem Cell Research Information website at: http://stemcells.nih.gov/.

Please Note: Federal funds may not be used for the creation of a human embryo for research purposes or research in which a human embryo is destroyed, discarded or knowingly subjected to greater than minimal risk of injury or death.

The Guidelines allow for federal funding of research using human embryonic stem cells (hESCs) derived from human embryos created using in vitro fertilization for reproductive purposes and no longer needed for these purposes. Institutions proposing research using hESCs derived from embryos donated in the United States after the effective date of the Guidelines may use hESCs that are posted on the new NIH Registry or may establish eligibility for NIH funding by demonstrating compliance with the specific procedural requirements of the Guidelines by submitting an assurance with supporting documentation (described in the Guidelines) to the NIH for administrative review. The Guidelines also allow certain uses of induced pluripotent stem cells for research.

The Guidelines permit use of hESCs derived from embryos donated outside the United States either before, on, or after the effective date of the Guidelines. Institutions that seek NIH funding for research involving hESCs derived from embryos donated outside the U.S. must adhere to the processes and criteria described in the Guidelines.

NIH has established a new Registry listing hESCs eligible for use in NIH funded research. All hESCs that have been reviewed and deemed eligible by the NIH in accordance with the Guidelines will be posted on the NIH Registry at: http://grants.nih.gov/stem_cells/registry/current.htm.

Prior to expending NIH funds, a funding recipient must assure NIH that hESCs involved in the funded project appear on the NIH Registry. Such assurances should be provided when endorsing applications and progress reports submitted to NIH for projects using hESCs. In addition, NIH clarified in a July 15, 2009 Notice that use of grant funds for hESC research will not be approved, and no new uses of hESCs may be initiated in ongoing funded studies, until the hESC line(s) to be used is approved through the new NIH process and listed in the Registry. For hESC lines that an institution proposes for addition to the Registry, the institution is required to submit an assurance providing that the donation of the embryo from which the cell line was derived met the eligibility requirements of the Guidelines.

The Guidelines advise that the following research is not eligible for NIH funding:

·  research in which hESCs or human induced pluripotent stem cells are introduced into non-human primate blastocysts;

·  research involving the breeding of animals where the introduction of hESCs or human induced pluripotent stem cells may contribute to the germ line;

·  research involving the derivation of stem cells from human embryos is prohibited by the annual appropriations ban on funding of human embryo research (otherwise known as the Dickey Amendment);

·  research using hESCs derived from other sources, including somatic cell nuclear transfer, parthenogenesis and/or embryos created using in vitro fertilization and created for research purposes.

Federal regulations for the Protection of Human Subjects, 45 C.F.R. 46, Subpart A and University Policy establish safeguards for individuals who are the sources of many human tissues used in research, including non-embryonic human adult stem cells, human induced pluripotent stem cells and, in certain circumstances, hESCs. When research involving biological material from a living individual constitutes human subject research, Institutional Review Board approval and informed consent are required prior to initiation of the research.

Research involving the use of biological material, such as cells derived from human embryos, may meet the definition of human subject research when the material can be linked to specific living individuals by the investigators either directly or indirectly through coding systems. In certain circumstances, IRB review and approval may be required for research involving hESCs.

The description of the Guidelines set forth above is qualified in its entirety by reference to the full terms and provisions of the Guidelines, which are available at: http://stemcells.nih.gov/policy/2009guidelines.htm.

Please Note: The Guidelines apply to the expenditure of NIH funds (as opposed to state funds or public monies) for research using hESCs and certain uses of induced pluripotent stem cells. The Guidelines do not alter or in any way affect ASU’s obligation to comply with Arizona law.

University Requirements

No hESCs may be created, derived, obtained, possessed or used by any person employed by, enrolled at or otherwise associated with the University or its programs unless the scientific protocol describing the proposed use of such embryonic stem cells has been reviewed and approved through the Office of Research Integrity and Assurance (ORIA).

The ORIA will coordinate a review of proposed activities involving hESCs among the relevant University research regulatory review committees such as the Institutional Review Board (for research with human subjects), the Institutional Animal Care and Use Committee (for research with laboratory animals), or the Institutional Biosafety Committee (for research using recombinant DNA, infectious or select agents).

Institutional Review Board Process

IRB review and approval is conducted in accordance with all relevant University policies and federal regulations. The IRB is responsible for determining that all biological materials proposed for use are obtained with the voluntary, informed consent of the donor or the family of the donor (where the donor is deceased or not capable of providing legally effective, informed consent).

Questions can be directed to the Office of Research Integrity and Assurance at or by calling the Director at 480-965-6788.