Stem Cells: Ethics and Oversight May 24, Sidney H. Golub, Ph.D. Interim Director Sue & Bill Gross Stem Cell Research Center

Transcription

1 Stem Cells: Ethics and Oversight May 24, 2017 Sidney H. Golub, Ph.D. Interim Director Sue & Bill Gross Stem Cell Research Center

2 Nobel Laureates 2012 John Gurdon Shinya Yamanaka

3 Pluripotent Stem Cell PLURIPOTENT STEM CELLS

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5 Human Stem Cells Ethical Issues Blastocysts as a potential human life Respect for fetal-embryonic materials Nuclear transfer technology raises the possibility of human reproductive cloning. Use of stem cells to make gametes Research use of human-animal chimeras might alter our definition of human. Defining the rights of the donors of the genetic material. Fair distribution of costs, risks, benefits Access to unproven or unapproved clinical treatments

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7 California Proposition 71: Stem Cell Research and Cures Initiative Passed in 2004 with 59% statewide, 52% in Orange County. Authorized $3 billion in 10 years toward stem cell research (annual spending limit of $350 million). Established constitutional right to conduct stem cell research; prohibited reproductive cloning. Created California Institute for Regenerative Medicine as a state agency with rule making authority.

8 Stem Cell Professional Regulation Guidelines from National Academy of Sciences (2005), ISSCR, other groups Consensus on key points: Local oversight (SCROs) Altruistic and consented donations of genetic materials No reproductive cloning, no reproducing chimeras Provenance of cells and tissues

9 Stem Cell Issues Requiring IRB Review Informed consent of donors of embryos, fetuses, gametes or somatic cells for derivation of stem cell lines or other research Informed consent of donors of oocytes for SCNT or parthenogenesis Transplantation safety issues Contaminants Production of biologically active molecules Tumorigenesis Inappropriate differentiation Immune rejection Other

10 UCI Human Stem Cell Research Oversight (hscro) Committee Initially appointed October members (stem cell science, clinical investigation, fertility medicine, ethics, science policy, patient advocates) Policy compliance and scientific review Coordination with other oversight bodies

11 CIRM Regulations Scope, definitions Activities Not Eligible for CIRM Funding Compliance SCRO Committee Membership and Function Acceptable Research Materials (including fetal materials) Special Considerations (including oocytes) Informed Consent Requirements Fairness and Diversity in Research

12 Activities Not Eligible for CIRM Funding Human reproductive cloning Transfer to a uterus of a genetically modified human embryo In vitro culture of a human embryo past 12 days or beyond appearance of primitive streak Introduction of hesc into non-human primate embryo Introduction of any stem cells of any origin into human embryo Breeding any animal which has received hesc

13 What to Do if I want to derive a hesc line Derivation of hesc lines from donated embryos is allowed. Must have hscro approval Must have an acceptable scientific rationale, appropriate expertise, acceptable plan for evaluation, distribution, storage of materials IRB and hscro will evaluate informed consent and risk-benefit No valuable considerations allowed (NIH and CA regulations)

14 What to Do if I want to use a hesc line in vitro hscro review (may be expedited) (varies by institution) Must document that line was acceptably derived NIH Registry, UK Cell Bank, or other approved guidelines Documented provenance of other cell lines

15 What Constitutes Acceptable Provenance? Proof of IRB or equivalent review and approval of original donation Proof of freely consented noncompensated donation (sample consent form) Procedures to guard confidentiality

16 What to Do if I want to use a hesc line in vivo No breeding of animals that have received hesc hscro approval necessary IACUC approval required No injection of human ESCs into nonhuman primate embryos

17 What to Do if I want to use fetal cells Strict federal and state regulations govern donation of aborted tissue No abortions for research only; decision to abort must precede decision to use for research; no compensation. All other fetus derived cells treated by hscro in a manner similar to ESCs and provenance must be documented

18 In vitro routes to pluripotent stem cells Nature June 13, 2013

19 The Special Case of ips: CIRM "Covered stem cell line" means a culture derived, human pluripotent stem cell population that is capable of: (1) sustained propagation in culture; and (2) self renewal to produce daughter cells with equivalent developmental potential. This definition includes both embryonic and non-embryonic human stem cell lines regardless of the tissue of origin. "Pluripotent" means capable of differentiation into mesoderm, ectoderm, and endoderm.

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21 What to Do if I want to use adult stem cells No hscro review required for: Mesenchymal stem cells Cancer stem cells Hematopoietic stem cells including cord blood stem cells Any other adult non-pluripotent stem cells IRB may ask hscro for scientific review

22 Regenerative Medicine Stem cell source Expansion Differentiation IVF Embryo Fetal cells ips Adult cells IRB Clinical Trials Phase I- safety Phase II- dose, effects Phase III- efficacy hscro Pre-clinical testing IACUC

23 Marketing Stem Cell Therapies Celltex patients Mexico therapy ad California ad

24 Turner and Knoepfler, Cell Stem Cell, 2016

25 Links and Contacts 2005 NAS Report CIRM Regulations UCI policies and procedures One page summary available Sidney Golub Mani Nistor, hscro Administrator