Juvenile Diabetes Patients Need Real Hope, Not Hype

Date: 03/02/2004

Embryonic Stem Cells, Cloning, Are Not Path To Cures

March 2, 2004

The Juvenile Diabetes Research Foundation (JDRF) plans to conduct a lobby day on Capitol Hill on Wednesday, March 3, reportedly to urge Congress to overturn President Bush’s policy on research using embryonic stem cells (ESCs).

Under the President’s policy, 15 existing embryonic stem cell lines are now available for federally funded research, and many more ESCs are in frozen storage and potentially available for creating new cell lines in the future.  However, federal funds are not used for research that requires destroying new human embryos for stem cells.

In case claims are made by JDRF that ESCs offer the only or best approach to curing juvenile diabetes, members of Congress should be in possession of some basic facts.

1. Embryonic stem cells have produced disappointing results for juvenile diabetes.

The latest example: While some studies have claimed progress in getting ESCs to differentiate into insulin-producing cells in culture, those claims are called into doubt in the most recent issue of the journal Diabetologia.  There researchers from the University of Calgary found that the insulin-producing cells derived from ESCs are not the “beta cells” needed to reverse diabetes.  While the cells produced some insulin, they did not do so in response to changes in glucose levels; when placed in mice they did not reverse diabetes but formed teratomas (tumors).1

This pattern — false hope, followed by a sobering dose of reality – has become a common feature of efforts to use ESCs for diabetes.  When researchers claimed to have produced cellular structures similar to pancreatic islets from ESCs in 2001, hopes ran high — but when placed in animals the cells provided no benefit, and all the animals died of diabetes.2 Then in 2003, other researchers showed that the first team probably had not managed to create insulin-producing cells at all – rather, the cells had only absorbed pre-existing insulin from their culture medium and released it again.3

Because of the difficulty of getting ESCs to differentiate into desired tissues, the risk of tumor formation, the genetic instability of ESCs in culture, and other problems, ESCs cannot be expected to provide treatments for juvenile diabetes anytime soon.

2. ADULT islet cells have reversed juvenile diabetes in hundreds of patients in clinical trials.

The most promising new treatment for juvenile diabetes in recent years is the “Edmonton protocol,” using adult pancreatic islet cells from adult cadavers.  It is ironic that this life-saving protocol had to be developed by Canadian researchers in Edmonton, Alberta, as many U.S. researchers were pursuing false leads in ESC research.

A recent news report notes that “of the 250 patients who have received the newest version of the transplant, more than 80 percent have been free from insulin shots or insulin pumps for more than a year.”4

The Edmonton protocol has two deficiencies: Insufficient volume of islet cells to treat all patients in need (each successful transplant may require cells from two or three cadavers); and patients must take immunosuppressive drugs for the rest of their lives to prevent tissue rejection.  But these problems are being solved, without use of ESCs.

3. Problems of supply and tissue rejection in the Edmonton protocol are being addressed.

– Harvard researchers, funded by the JDRF, have developed a new drug therapy that may enable islet cell recipients to retain their transplants permanently after only short-term use of anti-rejection drugs.  The drugs leave the germ-fighting abilities of the immune system intact, while preventing tissue rejection.5

– NIH researchers have shown that a prior transplant of adult bone marrow stem cells can prevent rejection of islet cell transplants in mice, without use of anti-rejection drugs.6

– University of Alberta researchers have been able to triple the number of beta cells obtained from islet cell donations, by culturing the islets with a growth factor.  Stem cells in the pancreatic tissue mature into beta cells, which have been shown capable of reversing diabetes in mice.7

For other advances in preventing tissue rejection see JDRF’s web site, www.jdrf.org.

4. ADULT stem cells are advancing to create entirely new therapies for juvenile diabetes.

– As the JDRF’s own newsletter reports: “Researchers in Canada have shown that transplanted adult stem cells from bone marrow can cause pancreatic tissue to repair itself, restoring normal insulin production and reversing symptoms of diabetes.”  The team has reversed diabetes in mice and hopes to move to human trials.8   Most amazing of all, the bone marrow cells did not turn into insulin-producing cells but induced “a natural regeneration of the body’s own islets,” and this “opens up a promising new avenue of research toward possible therapies using adult stem cells.”9

– Researchers at Massachusetts General Hospital have used adult cells from the spleen to regenerate insulin-producing cells and cure diabetes in mice.  Essentially the spleen cells “retrain” the body’s immune system to stop attacking its own islet cells, and new cells then naturally regenerate from the spleen cells and the body’s own cells, eliminating the need for an islet cell transplant.  The Boston Globe calls this “a surprising breakthrough that could soon be tested in local patients and pen a new chapter in diabetes research.”10

These and other advances promise new approaches to treating diabetes that require no destruction of human embryos.

5. “Therapeutic Cloning” is Useless in Treating Juvenile Diabetes

Proponents have long admitted that therapies based on ESCs may still prompt tissue rejection; they have proposed solving this problem by using cells from cloned embryos genetically matched to the patient.  But a leading cloning expert now admits that such “therapeutic cloning” is useless for treating autoimmune diseases like juvenile diabetes.

In a recent issue of the British Medical Journal, Ian Wilmut (the leader of the team that succeeded in cloning “Dolly” the sheep) writes:

“In any treatment regime we must avoid immunological rejectionof the transferred cells, but the immune response is likelyto vary from one disease to another… [S]everal of the conditions that are mentioned as candidates forcell therapy are autoimmune diseases, including type 1 diabetes.  In such cases transfer of immunologically identical cells toa patient is expected to induce the same rejection.11

In short, cells from cloning will have the same genetic makeup that prompts the body to attack its own cells as though they were foreign in the first place.  “Therapeutic cloning” is useless for juvenile diabetes.

ESCs have produced disappointing results for juvenile diabetes, and cloning is likely to be irrelevant to a cure.  But adult cell therapies are advancing to provide juvenile diabetes patients and their families with a healthy dose of well-grounded hope. 

  1. S. Sipione et al., “Insulin expressing cells from differentiated embryonic stem cells are not beta cells,” 47 Diabetologia 499-508 (2004).
  2. N. Lumelsky et al., “Differentiation of Embryonic Stem Cells to Insulin-Secreting Structures Similar to Pancreatic Islets,” 292 Science 1389-94 (2001).
  3. J. Rajagopal et al., “Insulin Staining of ES Cell Progeny from Insulin Uptake,” 299 Science 363 (2003).
  4. D. Wahlberg, “New islet cells put into liver,” The Atlanta Journal- Constitution, June 1, 2003, at www.ajc.com/health/content/health/special/0603/01exdiabetic_sidebar.html.
  5. JDRF Research News, “New Therapy Could Block Transplant Rejection With Short-Term Dosage,” October 29, 2003.  See X. Zheng et al., “Favorably tipping the balance between cytopathic and regulatory T cells to create transplantation tolerance,” 19 Immunity 503-14 (2003).
  6. News Release, American Society of Hematology, “Researchers Look to Stem Cell Therapy and Bone Marrow Transplants to Find a Cure for Diabetes,” December 8, 2003, at www.hematology.org/news/press/press_120903_5.cfm?pagemode=print.
  7. “U of A Makes Medical Breakthrough by Growing Insulin-Producing Cells,” The Daily Herald-Tribune (Grande Prairie, Alberta), August 1, 2003.
  8.  “Transplanted Bone Marrow Stem Cells Reverse Diabetes in Mice,” JDRF Countdown, Fall 2003, p. 6.  See D. Hess et al., “Bone marrow-derived stem cells initiate pancreatic regeneration,” 21 Nature Biotechnology 763-70 (2003).
  9. “New Mechanism Reverses Diabetes Symptoms,” Biotech Week, Editor’s Choice, July 30. 2003, p. 2.
  10. R. Mishra, “Juvenile diabetes cured in lab mice,” The Boston Globe, November 14, 2003, p. A2.  See S. Kodama et al., “Islet Regeneration During the Reversal of Autoimmune Diabetes in NOD Mice,” 302 Science 1223 (2003).
  11. I. Wilmut, “Human cells from cloned embryos in research and therapy,” 328 British Medical Journal 415-6 (2004).