by    0   0
AbledResearch Banner shows two scientists sitting by a microscope in a lab checking a vial of something. The image is in the foreground with a photo of the earth at sunrise as seen from space with the AbledResearch logo at the top.
AbledResearch Post banner shows a close-up photo of someone holding a lancet in one hand just after pricking the forefinger of their other hand to be able to take a blood sugar reading from the drop of blood on that finger. The headline reads: Abled research: Diabetes breakthrough: 15 years of work pays off getting stem cells to produce insulin.
AbledResearch photo shows an image of highlighted cells in a mouse. The caption reads: Human stem cell-derived beta cell islet-like clusters are producing insulin in a mouse.

A Giant Leap Forward Towards A Cure For Diabetes

Researchers never want to jinx their work by using black and white terms like ‘cure’, but Harvard stem cell researchers are tantalizingly close to what amounts to a cure for Type 1 Diabetes.

For millions of diabetics around the world, this is the biggest hope yet that might bring an end to daily insulin injections, the thousands of times each year they have to prick their finger with a lancet to test their blood sugar levels, or having to wear external insulin pumps while also fearing the disease’s potential long-term side effects such as blindness, kidney disease, amputations, strokes and heart attacks.

Doug Melton, Harvard’s Xander University Professor and a Howard Hughes Medical Institute investigator who leads the team of researchers at the lab that bears his name, says  “we are now just one-pre-clinical step away from the finish line.” That’s about as close to saying ‘cure’ as you can get without actually saying it.

And he’s got two good reasons for not wanting to over-state the possible outcomes before the definitive conclusions are reached – he has two grown children with Type 1 diabetes. When his, then, infant son Sam was diagnosed 23 years ago, Professor Melton dedicated his career to finding a cure for the disease.

In work that has just been published in the journal Cell, the Melton lab researchers have, after 15 years of trying and failing and trying and failing, have finally made a giant leap forward in diabetes research by being able to use human embryonic stem cells to produce human insulin-producing beta cells equivalent in most every way to normally-functioning beta cells.

As Professor Melton told the Harvard Gazette“There have been previous reports of other labs deriving beta cell types from stem cells. No other group has produced mature beta cells as suitable for use in patients,” he said. “The biggest hurdle has been to get to glucose sensing, insulin-secreting beta cells, and that’s what our group has done.”

Part of that hurdle is being able to produce those beta cells in the massive quantities needed, not only for cell transplantation, but also for pharmaceutical purposes. In this research, some stem cells came from human embryos, but Professor Melton’s team was able to reprogram human skin cells into a stem-cell-like-state  – a technique that is obviously more ethically acceptable.

The challenge with Type 1 diabetes is that it’s a metabolic response in the body’s immune system that goes rogue and kills off all the beta cells in the pancreas that produce insulin. About 150 million beta cells are needed for transplantation into a single patient and the final pre-clinical step involves protecting those cells from the immune system by using an implantation device. The device Melton is collaborating on with Professor Daniel G. Anderson and his colleagues at MIT and the Koch Institute has, so far, protected beta cells implanted in mice from immune system attacks for many months while they continue to produce insulin.

The lab-grown cells, currently being tested in primates, are just one step – albeit a few years – away from being clinically-trialled in humans.

And what do the Melton offspring think of this? Their father who also is Co-Scientific Director of the Harvard Stem Cell Institute and the University’s Department of Stem Cell and Regenerative Biology  — both of which were created more than a decade after he began his quest — said that when he told his son and daughter, they were surprisingly calm. “I think like all kids, they always assumed that if I said I’d do this, I’d do it,” he said with a self-deprecating grin.

Others are more willing to make a big deal about this. Richard A. Insel, M.D., the Chief Scientific Officer at the Juvenile Diabetes Research Foundation (JDRF) which along with the Helmsley Charitable Trust has contributed funding, says“JDRF is thrilled with this advancement toward large-scale production of mature, functional human beta cells by Dr. Melton and his team.”

Elaine Fuchs,  the Rebecca C. Lancefield Professor at Rockefeller University, and a Howard Hughes Medical Institute investigator who is not involved in the work, hailed it as “one of the most important advances to date in the stem cell field.”

Jose Oberholzer, Associate Professor of Surgery, Endocrinology, and Diabetes, as well as Bioengineering, at the University of Illinois at Chicago, Director of the Islet and Pancreas Transplant Program and Chief of the Division of Transplantation, called the discovery bigger than the discovery of insulin and says the work “will leave a dent in the history of diabetes. Doug Melton has put in a lifetime of hard work in finding a way of generating human islet cells in vitro. He made it. This is a phenomenal accomplishment.”

Felicia W. Pagliuca, Jeff Millman and Mads Gurtler of the Melton Lab are co-first authors on the Cell paper.

Other funding for the research, for which Professor Melton and his colleagues are extremely grateful, came from the National Institutes of Health, The Harvard Stem Cell Institute, the JPB Foundation, and Howard and Stella Heffron.

Description of Video

The beginning shows a spinner flask containing red culture media and cells, the cells being too small to see. Inside the flask you can see a magnetic stir bar and the flask is being placed on top of a magnetic stirrer. 

This is followed by a time-lapse series of magnified images showing how cells start off as single cells and then grow very quickly into clusters over the next few days. The size of the clusters is the same as the size of human islets at the end.

The final image shows 6 flasks, enough for 6 patients, spinning away. If you look closely, you can see particles spinning around, the white dust or dots are clusters of cells, each containing about 1000 cells.

Credit: Mikey Segel

AbledResearch photo shows Harvard's Xander University Professor Doug Melton whose team has announced a major breakthrough in Diabetes Research.
Abled.com Banner: Related Coverage.

Transcript of NPR Report

Copyright ©2014 NPR. For personal, noncommercial use only. See Terms of Use. For other uses, prior permission required.

MELISSA BLOCK, HOST:

We’re going to turn now to health news of an advance that could eventually lead to a cure for diabetes. Before the discovery of insulin in the 1920s, diabetes was a feared disease that often led to a rapid death. Today, insulin injections to control blood sugar levels are a mainstay of therapy for Type 1 diabetes. They’re also used by many with the Type 2 form of the disease.

But insulin injections aren’t a cure. People can still suffer complications, including heart attacks and blindness. NPR’s Rob Stein reports on work by scientists at Harvard that could someday eliminate the need for injections.

ROB STEIN, BYLINE: For Harvard cell biologist Doug Melton, the search for something better than insulin shots for diabetes has been a very personal quest.

DOUG MELTON: My six-month-old son Sam came down with diabetes some 20 years ago. And some years later, my 14-year-old daughter Emma also came down with Type 1 diabetes. Since that time, I don’t know how to say it except that I’d do what any parent would do, is to say that I’m not going to put up with this. And I want to find a better way.

STEIN: Now, Melton and his colleagues are reporting in the journal Cell that they finally found that better way. They figured out how to mass-produce the kind of cells that naturally produce insulin in the body – cells that could be transplanted into patients so their bodies could control their blood sugar normally.

MELTON: We are reporting the ability to make hundreds of millions of cells – the cell that can read the amount of sugar in the blood which appears following a meal and then squirt out or secrete just the right amount of insulin.

STEIN: They did this using human embryonic stem cells. They can be turned into almost any kind of cell in the body. But for 15 years the researchers tried and failed and tried and failed to find just the right mix of chemical signals that would coax human embryonic stem cells into becoming insulin cells. Finally, they came up with a recipe that works.

MELTON: A short way of saying this might be like if you were going to make a very fancy kind of new cake – like I do know, a raspberry chocolate cake with vanilla frosting or something. You pretty much know all the components you have to add. But it’s the way you add them and the order and the timing, how long you cook it, et cetera. The solution to that just took a very long time.

STEIN: And when Melton and his colleagues transplanted the cells into mice with diabetes, the results were clear and fast.

MELTON: We can cure their diabetes right away in less than 10 days. This finding provides the kind of unprecedented cell source that could be used for cell transplantation therapy in diabetes.

STEIN: Other scientists are hailing the research as a big advance.

MELTON: Well, it’s a huge landmark paper. I would say it’s bigger than the discovery of insulin.

STEIN: Jose Olberholzer is a professor of bioengineering at the University of Illinois.

JOSE OLBERHOLZER: The discovery of insulin is important and certainly saved millions of people. But it just allowed patients to survive but not really to have a normal life. The finding of Doug Melton would really allow to offer them really something that I would call a functional cure, you know. They wouldn’t really feel any more being diabetic if they got a transplant of these kinds of cell.

STEIN: Now, Melton and others caution there’s still a lot more work to do before they’re ready to try this in people with diabetes. For one thing, they need to come up with a way to hide the cells from the immune system, especially for people with Type 1 diabetes, so the immune system doesn’t attack and destroy the cell. Melton and his colleagues are working on that. And they think they may have come up with a solution – a kind of protective shell.

MELTON: We’re thinking about it as sort of like a teabag were the tea stays inside, the water goes and then the dissolved tea comes out.

STEIN: And so if you think about a teabag analogy, we would put ourselves inside this teabag.

STEIN: But that’s not the only problem. Some people have moral objections to anything that involves human embryonic stem cell research because it destroys human embryos. Daniel Sulmasy, a doctor and bioethicist at the University of Chicago shares that view.

DANIEL SULMASY: If, like me, someone considers the human embryo to be imbued with the same sorts of dignity that the rest of us have, then in fact this is morally problematic. It’s the destruction of an individual unique human life for the sole purpose of helping other persons.

STEIN: Melton says he’s also found a way to use another kind of stem cell – cells that don’t destroy any embryos. He’s trying to figure out if they work as well and hopes to start testing his insulin cells in people with diabetes within three years. Rob Stein, NPR News.

Copyright © 2014 NPR. All rights reserved. No quotes from the materials contained herein may be used in any media without attribution to NPR. This transcript is provided for personal, noncommercial use only, pursuant to our Terms of Use. Any other use requires NPR’s prior permission. Visit our permissions page for further information.

NPR transcripts are created on a rush deadline by a contractor for NPR, and accuracy and availability may vary. This text may not be in its final form and may be updated or revised in the future. Please be aware that the authoritative record of NPR’s programming is the audio.

Click the + sign to the right of AbledHearing to close this window.

Abled.com Banner: Related Videos.

Previous Breakthrough Discovery About New Hormone To Treat Type 2 Diabetes

In 2013, HSCI Co-Director Doug Melton and postdoctoral fellow Peng Yi discovered a hormone that holds promise for a dramatically more effective treatment for type 2 diabetes. The researchers believe that the hormone might also have a role in treating type 1, or juvenile, diabetes.

Harnessing The Potential Of Stem Cells

HSCI Co-Director Doug Melton speaks at TEDxBeaconStreet in 2013 about the potential of stem cell biology for regenerative medicine, with a focus on finding new treatments for diseases such as diabetes.

Related Agencies Banner
AbledEvents Public Service Ad for Worlf Diabetes Day, 14 November, 2014. Click here to go to the International Diabetes Federation website for the event.
Abled Public Service Ad link to the International Diabetes Federation
Abled Public Service Ad for The International Diabetes Federation 2015 World Congress in Vancouver, Canada. Click here to go to the Congress website.
Abled.com Public Service Ad for the European Coalition for Diabetes. Click here to go to their website.
Abled Public Service Ad link to the Asia DIabetes Foundation
Abled Public Service Ad link to the American DIabetes Association.
Abled Public Service Ad link to the Canadian DIabetes Association
Abled.com Public Service Ad for DIabetes UK. Click here to go to their website.
Abled.com Public Service Ad for Diabetes Australia.
AbledResearch More Posts Banner.
AbledResearch Post banner shows a silhouette of Abled.com Co-Founder Laura Meddens walking with her Seeing Eye guide dog Wagner against a magnified golden-hued image of Wagner's T-Cells as seen through an electron microscope. The headline reads: Cancer: A Brave Guide Dog's Legacy In T-Cell Immunotherapy Research for Humans.
AbledNews - More Posts banner
AbledConditions post link banner shows a background graphics montage of slides from a brain CT scan slightly blurred behind a side profile view of an X-ray of a person's head and shoulders with the brain area highlighted with an orange glow. The headline reads: AbledConditions: Alzheimer's Disease: Ground-breaking treatment at UCLA improves failing memory. Click here to go to the post.
AbledAlert link banner Shows a photograph of healthcare workers dressed in turquoise blue surgical gowns , hairnets and pink medic al gloves set against a world map and chart showing data on Ebola outbreaks since 1976. The headline reads: Abled Alert: Outbreak: Tracking the deadliest yet. Click here to go to our Special Ongoing Coverage on the Ebola Virus outbreak in West Africa.
AbledALERT-Outbreak post link banner shows 13 year old Will Cornejo of Lone Tree, Colorado breathing with the help of an oxygen mask while lying in a hospital bed, while text in the foreground reads: Enterovirus. The headline reads: Outbreak: Virus Primer For Parents. Click here to go to the report.
AbledAlert link box shows a photograph of an Asian Tiger Mosquito set against a transparent red layer covering a map of the Caribbean region with the word Chikungunya in WHite at the top. The headline reads: Outbreak: 'Contorted With Pain Virus. CLick here to go to our special ongoing coverage.
Abled Warriors post link banner shows sketches of the American Veterans Disabled For Life Memorial dedicated on October 5, 2014 in Washington, D.C. A stone wall bears the name of the inscribed into it in the background while we see two men observing an eternal flame in the granite star centerpiece of the memorial while we see the left profile of an Armed Forces officer and another man in the center foreground looking off to the left. The headline reads: AbledWarriors: Moving Memorial: The Dedication. Click here to go to the post.
Abled Conditions Special Report link banner shows a black and white photo of Robin Willieams kneeling on one knee and clasping his hands around his other leg which is bent at the knee. He is looking at the camera with an impish grin on his face. There is a candle burning in the right foreground. The Headline reads: AbledConditions: Depression | Parkinson's: Tears of a Clown. Click here to go to our Special Report.
AbledRx link box shows a photo of various Aspirin bottles and boxes. The headline reads: AbledRx; Aspirin: Linked to Huge Cut in Cancer. Click here to go to the post.
AbledCauses link box shows Nick Auden hugging his three children. The headline reads: Locky's Dad: His 'Right To Try' Legacy. Click here to go to the story.
AbledKids post link box shows a screen grab from a new App for emergency preparedness for children produced by Sesame Workshop, the prodders of Sesame Street. It shows a video frame featuring Grover in a construction helmet. The headline reads: AbledKids: Sesame Street: Disaster Apps for Kids. Click here to go to the post.
AboutAbled link Banner shows Abled Co-Founder Laura Meddens looking out at the seaside at sunset in Curaçao with the text Laura Meddens: An Abled Vision For Global Accessibility, Inclusion and Equality. Click here to go to the AboutAbled page.
Return to the Abled.com Homepage banner. Click here.

thoughts on this post

Back to Top