February 4, 2005, Summary

NIH Stem Cell Task Force

Members Present:

James Battey, NIDCD (Chair); Arlene Chiu, NIBIB; Robert Hammond, NIDDK; Ron McKay, NINDS; Mahendra Rao, NIA; Richard Tasca, NICHD; John Thomas, NHLBI; Marion Zatz, NIGMS

Other Participants:

Tony Beck, NCRR; Laura Cole, NIDCD; Don Fink, FDA; Tom Johnson, OD/OSP Lisa Montney, NIDCD; Walter Schaffer, OER; Paul Sheehy, NIGMS; Jack Spiegel, OD/OTT; Baldwin Wong, NIDCD; Heather Zawalick, NINDS

I. Welcome

Dr. Battey welcomed the participants to the twelfth meeting of the NIH Stem Cell Task Force, and thanked them for their continued efforts. Once again, Dr. Battey reviewed the basic findings and implications of the February 2005 Nature Medicine paper by Martin et al. (PDF; get Adobe Reader) "Human embryonic stem cells express an immunogenic nonhuman sialic acid." Interested Task Force members may contact Dr. Battey via email to learn how he has responded to Press questions about this paper.

Approval of Meeting Minutes

The Task Force approved the text of the October 27, 2004, meeting minutes, which will be posted on the NIH Stem Cell website at http://stemcells.nih.gov/policy/taskForce/tfSummaries/2004_10_27tfs.asp.

II. Update of RFA for Centers of Excellence

Dr. Sheehy described NIH's progress on the RFA on Centers of Excellence for Translational Stem Cell Research. Letters of Intent in response to this initiative are due to NIH on February 24th, and the potential applicant pool seems promising. One question that potential applicants have been asking is how they should describe non-grant supported resources provided by their home institute (and not being included in the grant request for support). Potential applicants were told by NIH that these grants could leverage support from other sources. NINDS is referring questions on non-grant support to the following text in the RFA which was published in the NIH Guide for Grants and Contracts:

Task Force members should refer any questions from potential applicants to Dr. Sheehy.

III. Update of RFP for Stem Cell Bank

Dr. Battey gave a brief update on the RFP based on a written summary submitted by NCRR's John Harding. The announcement was posted on NHLBI's website and FedBizOpps in December. The Letter of Intent is due to NIH in February, the proposals are due in March, and the applications will be reviewed in Spring/Summer. NIH expects to award the contract in September 2005.

Dr. Battey reported that the NIH has established an oversight group to coordinate the activities of the extramurally funded Stem Cell Bank and the intramural NIH Stem Cell Unit to avoid duplication of efforts. Dr. Ron McKay will chair the oversight group. Dr. McKay reported that the huge amount of characterization work that still remains on the human embryonic stem cell (hESC) lines available on the NIH Human Embryonic Stem Cell Registry will allow the Bank and the Unit to specialize in their efforts.

IV. Stem Cell Characterization Data

Dr. Rao presented unpublished data on his efforts to determine whether hESC lines on the NIH Registry are stable in long-term culture and whether they are similar to one another. He reported that overall, mouse ESCs are more stable than any mouse adult stem cell line examined, and ESC mitochondrial stability is very good. However, Dr. Rao's group is finding differences between early passage and late passage cells from the same line when examined at the finer level. A majority of the hESC lines he examined showed differences in 4 categories: methylation, high resolution mapping, single nucleotide polymorphism (SNP,) and X-chromosome inactivation. These differences may have implications for intellectual property and biology/clinical utility because they predict that later passages are different when compared to earlier passages.

Dr. Rao serves as the project officer for NIA's contract with the American Type Culture Collection (ATCC) to study the NIH hESC Registry lines. They are examining the lines' karyotype and telomerase activity and are trying to obtain other hESC lines for comparison. ATCC would like to distribute the WiCell lines under a "Deposit and Store" agreement, in which they handle only distribution within the United States and have no rights or licensing fees related to the cells. ATCC is currently distributing BresaGen BG01V, which is a variant and subline to the BG01 parent line. Because of a chromosomal variation, BG01V is not subject to the WiCell licensing fee. The variant line is a valuable resource for researchers and for-profit businesses who cannot afford the high WiCell licensing fee.

Standardized Resources

Dr. Rao reported that several groups are working to develop standardized resources for studying hESCs. These include:

• Bresagen's variant line BG01V, distributed by ATCC
• Cellartis—qPCR quantitative PCR to show how cells differentiate
• FDA—developing an array using long oligonucleotide probes; useful for detecting less frequently-expressed genes; see Blood 103:2956–2964 (PDF; get Adobe Reader).
• R&D Systems—antibodies to look at hESC cell surface markers

V. Stem Cell Intellectual Property Issues

Dr. Jack Spiegel reported that Geron Corporation was issued another U.S. stem cell patent at the end of 2004. Their latest patent covers the use of feeder-free conditions. The wording of the patent is very broad and includes hESCs that were weaned off feeder layers. Thus, for-profit scientists wishing to grow hESCs under feeder-free conditions must first pay WiCell's licensing fee and then pay Geron's licensing fee. Dr. Spiegel expects that academic researchers will either not be required to pay a fee or, if necessary, request relief/rapid action for nonprofit entities, similar to the current terms NIH negotiated with WiCell.

In light of these events, Dr. Battey proposed convening a meeting with the NIH OTT and several IC directors whose institutes fund the majority of the hESC research at NIH. Participants will discuss how NIH might pursue IP rights for stem cell technologies developed in the NIH Division of Intramural Research.

VI. Update of the NIH Stem Cell Report

Mr. Wong reported that his office is working to update the NIH Stem Cell report, Stem Cells: Scientific Progress and Future Research Directions, to be coordinated by Dr. Laura Cole. Dr. Cole reported that the report is to take the form of a collection of review articles by well-known experts in several areas of stem cell research. Dr. Cole also proposes to include an appendix describing current technology for labeling transplanted stem cells to permit tracing of their fate, with the author to be determined. Task Force members agreed to assist in reviewing those chapters already submitted.

Task Force members suggested taking advantage of the web-based format of the report to add new chapters on an ongoing basis, as new areas of research take shape. Members also suggested an author for the appendix on labeling transplanted cells and additional chapters, including limbal stem cells from the eye, cord blood stem cells, mesenchymal stem cells, and liver stem cells.

VII. Identification of Issues for Task Force Consideration—around the table

Dr. John Thomas reported that the recent science advance by Douglas Losordo which appeared in Nature Medicine (Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction) was funded in part by NHLBI. Dr. Thomas also reported that the NIH will re-issue the Program Announcement for the T15 Training Courses for stem cells. Dr. Battey will contact the IC Directors to encourage their participation in cofunding the PA.

Dr. Robert Hammond reported that NIDDK received a letter from an NIDDK grantee describing a proposed project to create a bacterial artificial chromosome (BAC) library from two hESC lines. Such a library would facilitate the development of knockouts in the hESC lines, providing models for human diseases. Since this proposal describes a trans-NIH resource, clearly not specific only to a particular IC, the Stem Cell Task Force recommended that it be considered by the NIH Stem Cell Implementation Committee at their next meeting.

Dr. Don Fink reported that the FDA has received several IND applications for heart repair using human stem cells.

Dr. Tony Beck reported that the T15 Training Grant/R24 Supplement Grantee joint annual meeting will precede the ISSCR meeting in San Francisco in June 2005. He asked NIH Stem Cell Task Force members to send questions for grantee consideration prior to the meeting, in order to focus their discussions.

The Task Force suggested that a progress report on the NIGMS P20 Exploratory Centers be presented at the next meeting. The meeting adjourned at 11:05 a.m.

The next meeting of the NIH Stem Cell Task Force is tentatively scheduled for Friday May 6, 2005, 9:00–11:00 a.m. in Building 31, Room 3C05.

If you have questions about the Task Force, please contact:

Science Policy and Planning Branch
National Institute on Deafness
and Other Communication Disorders, NIH
Bethesda, MD 20892
Phone: (301) 402-2313
Fax: (301) 402-2265
E-mail: stemcell@mail.nih.gov