Future of transplant medicine : Stem Cells

Regrowing Organs
3 min - Jan 7, 2011

Dr. Manny sits down with physicist, Dr. Michio Kaku, to talk about the future of transplant medicine and how doctors are regrowing organs in labs

,'

,

A new study reports on the success of growing human liver cells; To be used for transplantation

Scientists grow human liver tissue to be used for transplantation

Science Centric 21 January 2011 19:11 GMT

A new study reports on the success of growing human liver cells on resorbable scaffolds made from material similar to surgical sutures. Researchers suggest that this liver tissue could be used in place of donor organs during liver transplantation or during the bridge period until a suitable donor is available for patients with acute liver failure. Findings of this study appear in the February issue of Liver Transplantation, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases.

As of January 2011, more than 16,000 Americans are on the waiting list to receive a suitable liver according to data from the Organ Procurement and Transplantation Network. Liver cell (hepatocyte) transplantation offers a possible solution in overcoming the organ shortage. In addition, liver cells have excellent regenerative potential making liver cell transplantation a viable therapeutic approach for patients with metabolic defects or fulminant hepatic failure as the native liver is preserved while liver dysfunction may resolve as regeneration occurs.

Dr Joerg-Matthias Pollok, Head of the Laboratory for Tissue Engineering and Cell Transplantation, Department of Hepatobiliary and Transplantation Surgery at the University Medical Centre in Hamburg, Germany explains, 'Currently isolated liver cells are used for liver cell transplantation, but these cells suffer during cell isolation and cryopreservation, which is one reason there is limited success with this type of transplant procedure.' In applying their tissue engineering approach, the German researchers were able to successfully create new liver tissue providing a potential solution to the obstacles challenging liver cell transplantation.

The team isolated liver cells from 12 human liver specimens with a viability of 82%. After a two-day culture period, liver cells formed tightly packed cellular aggregates, called spheroids, and took on a liver-like appearance. Human liver cells were distributed across a three-dimensional porous structure of the polymer scaffolding. From day two to four, the average number of spheroids more than doubled from 18 to 41 per visual field. 'Our experimental model represents a promising technique to culture human liver cells and prepare them for transplantation on a biodegradable polymer scaffold into the peritoneal cavity,' concluded Dr Pollok. 'Further studies are underway to confirm our results and may ultimately offer viable clinical options for liver cell transplantation in the future.'

A related editorial also published in Liver Transplantation this month acknowledges the huge clinical potential for liver cell transplantation. Humphrey Hodgson, M.D., from the UCL Medical School in London wrote that a number of liver cell transplantation approaches have been used in uncontrolled trials, but effective clinical protocols have not yet been established. He noted that while no technique has emerged as a proven clinical approach, the use of human rather than rodent cells as demonstrated by Pollok et al. is an important step in advancing the science behind liver cell transplantation.

Source: Wiley-Blackwell

This study is published in Liver Transplantation. Media wishing to receive a PDF of this article may contact healthnews@wiley.com.

Full citation: "Primary Human Hepatocytes on Biodegradable PLLA-Matrices: A Promising Model for Improving Transplantation Efficiency Using Tissue Engineering." Eva Török, Marc Lutgehetmann, Jeanette Bierwolf, Stefan Melbeck, Jochen Düllmann, Bjoern Nashan, Peter X. Ma, Joerg M. Pollok. Liver Transplantation; Published Online: October 11, 2010 (DOI: 10.1002/lt.22200); Print Issue Date: February 2011.
http://onlinelibrary.wiley.com/doi/10.1002/lt.22200/abstract.

Editorial: "Liver Cell Implants – A Long Road." Sanjaya Humphrey Hodgson and Clare Selden. Liver Transplantation; Published Online: January 10, 2011 (DOI: 10.1002/lt.22245); Print Issue Date: February 2011. http://onlinelibrary.wiley.com/doi/10.1002/lt.22245/abstract.

About the Journal
Liver Transplantation is published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society . Since the first application of liver transplantation in a clinical situation was reported more than twenty years ago, there has been a great deal of growth in this field and more is anticipated. As an official publication of the AALSD and the ILTS, Liver Transplantation delivers current, peer-reviewed articles on surgical techniques, clinical investigations and drug research — the information necessary to keep abreast of this evolving specialty. For more information, please visit Liver Transplantation.

About Wiley-Blackwell
Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world's leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols.

For more information, please visit http://www.wileyblackwell.com/ or our new online platform, Wiley Online Library (wileyonlinelibrary.com), one of the world's most extensive multidisciplinary collections of online resources, covering life, health, social and physical sciences, and humanities.
,
,

Custom-made hearts, lungs, kidneys, and other organs could revolutionize organ transplantation

Watch the full episode. See more NOVA scienceNOW.

Coming Soon

Check Local Listings

Replacing Body Parts
Custom-made hearts, lungs, kidneys, and other organs could revolutionize organ transplantation.

Program Description
Scientists are learning how to grow custom-made body parts so they can be ready when you—and your vital organs—start falling apart. At the University of Minnesota, Doris Taylor and her colleagues strip organs of their cells, reseed the organ "skeletons" with living cells, and watch as the organs start working right in front of their eyes.

Airs January 26, 2011 on PBS

Regenerative Medicine: Growing more than 20 types of tissues

From Standford

Regenerating organs from scratch

By Bruce Goldman
Tony Atala, MD, was the guest speaker yesterday at Stanford's 5th annual Oscar Salvatierra, Jr., M.D. lecture in transplantation. Atala, a pediatric urologist and the director of the Wake Forest Institute for Regenerative Medicine in Winston-Salem, NC, is a highly regarded tissue-engineering pioneer. He and his colleagues are now growing more than 20 types of tissues, with some notable successes in delivering them to patients with failing or defective organs.

In general, the approach involves creating a scaffold that can be seeded either with the patient's cells, if those of the appropriate type can be harvested, or with stem cells.

The scaffold itself can be the collagenous extracellular matrix of a donor organ whose cells have been removed with detergents, or it can be a wholly artificial construct - Atala's team has been able to create off-the-shelf organ scaffolds using a desktop inkjet printer. The printer is modified to spray not ink but a cell-filled gel, layer by layer, according to a computer program. The output is an intricate three-dimensional structure. When fetal cardiomyocytes - the cells that compose heart muscle - were seeded onto a heart-specific scaffold generated this way, the resulting entity started beating within four hours, Atala told his attentive audience.

As for which kinds of starter-material cells to use, Atala spoke in some detail about a promising class of stem cells isolated from amniotic fluid and placenta. These cells seem somewhat more mature than either embryonic stem (ES) cells or induced pluripotent stem (iPS) cells. Yet they multiply robustly and have, so far, been shown capable of differentiating into bone, cartilage, liver, lung, kidney, blood, pancreatic beta cells, intestine and cardiac and endothelial tissues. On the other hand, they do not form teratomas or tumors, a major drawback of both ES and iPS cells. Cherry on the sundae: They appear to suppress immune rejection.
Sounds like progress to me.

I've said it before. One reason I love my job so much is that it's the opposite of writing obituaries.

Regenerative medicine workshops to debut at TERMIS North America Annual Conference

WINSTON-SALEM, N.C. – Tuesday, Nov. 16, 2010 –

Tying in with this year's conference theme, "Where Discovery Meets Innovation," two new pre-conference workshops will debut at this year's TERMIS-North America 2010 Conference and Expo (December 5-8, 2010) in Orlando, Fla.

The TERMIS (Tissue Engineering & Regenerative Medicine International Society) North America meeting is hosted by the Wake Forest Institute for Regenerative Medicine, and chaired by Anthony Atala, M.D., institute director. James Yoo, M.D., Ph.D., an associate director and chief scientific officer at the institute, is the meeting's scientific program chair.
The workshops, which are co-sponsored by Forecast Technology Group Inc., will offer attendees an opportunity to learn at a more in-depth level about the latest advancements in bone tissue regeneration and biomaterials for cell therapy.

Bone Tissue Engineering and Regeneration, will be held from 7 a.m. to 5 p.m. on Sunday, Dec. 5, and will focus on how to accelerate the translation from discovery science to clinical applications, highlight solutions that have been investigated to date, and discuss specific, practical clinician-based approaches versus opting for off-the-shelf products. The scientific organizing committee includes: Jeremy Mao, D.D.S., Ph.D., professor of dental medicine, Columbia University, Regis O'Keefe, M.D., Ph.D., professor of orthopaedics, University of Rochester, and Fei Wang, Ph.D., program director, Musculoskeletal Tissue Engineering and Regenerative Medicine Program, the National Institute of Arthritis and Musculoskeletal and Skin.

Hyaluronan Biomaterials for Cell Therapy, will also debut on Sunday, Dec. 5 from 1 p.m. to 5 p.m. Co-sponsored by Glycosan BioSystems, and organized by Glenn Prestwich, Ph.D., presidential professor of medicinal chemistry at the University of Utah, this educational program will focus on the chemistry and engineering of novel HA-derived biomaterials, by highlighting the design criteria for clinically useful HA biomaterials, as well as preclinical and clinical applications of HA-derived biomaterials.

A post-conference workshop, TERMIS-NA NIH Grant Writing, will close the annual conference on Wednesday, Dec. 8. The workshop, scheduled for noon to 6 p.m, is designed to help investigators write successful National Institutes of Health (NIH) grant applications through better understanding of the NIH grant processes, especially in light of the new application and review format. Each component of the new NIH application format will be discussed in detail and tips on how to interpret summary statement and prepare resubmission will be provided. Faculty members include experienced, funded investigators with first-hand NIH review experience. NIH program directors and review officers will be on hand to discuss NIH funding opportunities and review procedures. Students, postdoctoral fellows, clinical fellows, and faculty members are encouraged to attend to gain information and knowledge which will aid them to write competitive NIH grant applications.

The goal of these programs is to offer additional educational opportunities for conference and non-conference participants. More than 35 experts will share case studies and knowledge. Registration for all workshops is separate from the main conference. Due to limited seating, advanced registration is encouraged. For more information, visit www.termis.org/na2010.
###

Media Contacts: Karen Richardson, krchrdsn@wfubmc.edu, 336-716-4453.

About TERMIS-NA 2010
The TERMIS (Tissue Engineering & Regenerative Medicine International Society) North America's general conference will cover a wide range of topics within the fields of tissue engineering, biomaterials, stem cells and regenerative medicine. The meeting is designed to foster interactions among basic scientists engaged in discovery and development, translational researchers who bring scientific discoveries to the clinical forefront, clinicians, and those engaged with funding, regulatory and commercial endeavors. The goal of the event is to present and exchange new results and advances in tissue engineering and regenerative medicine. Register now for the conference by visiting the conference website at http://termis.org/na2010 or contact Anita Caufield, Executive Producer, Forecast Technology Group Inc., anita@conferencestrategists.com.

About the Wake Forest Institute for Regenerative Medicine
The Wake Forest Institute for Regenerative Medicine (http://www.wfirm.org/) is an established center dedicated to the discovery, development and clinical translation of regenerative medicine technologies by leading faculty. The institute has used biomaterials alone, cell therapies, and engineered tissues and organs for the treatment of patients with injury or disease. The Institute is based at Wake Forest University Baptist Medical Center (www.wfubmc.edu), an academic health system comprised of North Carolina Baptist Hospital, Wake Forest University Health Sciences, which operates the university's School of Medicine, and Wake Forest University Physicians. The system is consistently ranked as one of "America's Best Hospitals" by U.S. News & World Report.

About Forecast Technology Group Inc, http://www.conferencestrategists.com/
Forecast Technology Group Inc. is the executive producer of TERMIS-NA's annual conference and the creator/producer of Innovation Discovery Labs (IDL), a custom-developed educational program designed especially for professional societies and the industries they serve. Forecast provides conference management and educational development services for a variety of professional associations, universities, and businesses.

*Liver Growing Body Parts *Regenerative medicine

In case You Missed It

.

Advances in regenerative medicine

.

July 2010

Advances in regenerative medicine means it's possible for damaged body parts to be regrown from human cells, and 60 Minutes featured the growing area of study.
The Wake Forest Institute for Regenerative Medicine is working on this with all kinds of organs and parts of the body and hopes to fight the fact people are dying while on the transplant wait list.

Dr. Anthony Atala of the Wake Forest Institute told CBS the goal is to "provide replacement tissues and organs that can be used to help [such patients] survive."
Atala says some body parts are easier to recreate than others, such as the ear, though the hope is eventually all body parts can be regenerated.
So far, human bladders have already been replicated based on cells and replaced into the body. Each replication takes approximately 6 to 8 weeks.

.

Nov 2010

.

Liver Regeneration:Opening The Door To New Treatments for Regenerating Liver and Bone Marrow

.

Also See :Skin cells transformed into blood

.

AASLD:Human Cells Grow on Animal Liver Scaffolds

.

Regenerating body parts lost by soldiers who have been injured in war is the topic of our story from McGowan Institute for Regenerative Medicine at the University of Pittsburgh. “Powder Regenerates New Muscle” covers the encouraging results of an experimental procedure using a biologic compound made from harvested pig bladder. Watch to see how the experimental powder, when placed near a wound, actually signals the human body to begin generating new cells and has already been effective for regenerating the human esophagus, in addition to muscle regeneration.

..

Salk scientists discovered how stem cells respond to nutrient availability

,

New method to create bioartificial organs

.

Stem Cells/Presented at AASLD

,

AASLD:Human Cells Grow on Animal Liver Scaffolds

By Kristina Fiore, Staff Writer, MedPage
TodayPublished: October 31, 2010
Reviewed by Robert Jasmer, MD;
Associate Clinical Professor of Medicine,
University of California, San Francisco

BOSTON -- Researchers reported here that they have pared down animal livers to their basic vascular structure and repopulated them with human liver progenitor and endothelial cells -- taking a small step toward ultimately creating completely bioartificial livers.

After a week in a bioreactor, human liver cells placed onto this liver "scaffolding" began to express signature proteins such as albumin, and the endothelial cells expressed von Willebrand factor -- clues that the cells were functioning normally, according to Pedro Baptista, PhD, PharmD, of Wake Forest University in Winston-Salem, N.C., and colleagues.

Baptista reported the group's findings during an oral session at the American Association for the Study of Liver Diseases meeting.

"We're looking into organ scaffolding because it offers a vascular system, and you can't really tissue engineer an organ without a vascular system," Baptista told MedPage Today.

"It's amazing because the cells recognize the chemistry of the matrix on their own and localize and attach in what we think are their native niches -- the endothelial cells attach to vascular structures and the hepatocytes attach in more parenchymal areas," he added.

Yet Baptista cautioned that the work is still very preliminary and his group is currently working on increasing the percentage of organ that gets repopulated with cells -- which currently stands at about 30%.

The purpose of creating bioartificial livers is to mitigate the organ donor shortage -- a persistent and growing problem in the U.S. During his talk, Baptista said the most recent statistics show that 109,000 people are awaiting organ transplants, 16,000 of whom are waiting for a donor liver.

Generating a liver scaffold has been done in the past -- and the technique can also be applied to other organs including the kidney and lungs -- but the organs had only been repopulated with animal cells.

To test the ability of growing human cells on these animal matrices, the researchers removed all existing cells from ferret livers with a detergent solution (Triton X-100 with a bit of ammonium hydroxide) to wash away cellular components such as membranes, nucleic acids, and cellular proteins.

That left behind an extracellular matrix that retains most of its microarchitecture, Baptista explained.

Next, the group seeded 70 million human liver progenitor cells and 30 million endothelial cells onto the matrix through the portal vein or vena cava, and left the organs in a bioreactor for a week.

During that time they found that the endothelial cells attached to the existing vascular channels, and the liver progenitor cells clustered throughout the bioscaffolding.

Baptista said that the "seeding is not quite there" at a 30% level, but his group is now looking at increasing the number of human cells initially infused -- perhaps to 300 or 400 million instead of 100 million.

The results still show, however, that the liver scaffold is biocompatible and can provide a sufficient substrate.

"It shows the cells are really able to recognize the native tissues and attach and engraft in those selected tissues," he said.

In fact, the liver cells were excreting higher levels of signature proteins including albumin and urea, and the endothelial cells expressed higher levels of von Willebrand factor and nitric oxide than comparator cells grown in Petri dishes, Baptista said.

He said a next step is to transplant the new organs back into animals to measure function and survival.

Another group, from Massachusetts General Hospital in Boston, which presented its findings during a poster session at the AASLD meeting, used the same scaffolding technology and retransplanted the livers back into rats.

They found similar 30% function in the new organs, but the transplanted animals only survived for eight hours, Basak Uygun, PhD, told MedPage Today.

She said in an interview that her team used large doses of blood thinner to prevent the clotting that's typical when a scaffolded organ is reperfused, which may have had an effect on mortality.

But when the livers remained outside of the animals, they functioned well for 24 hours but were not followed-up longer, she added.

The next step is to reperfuse greater than 30% of the matrix with functioning cells, Uygun added.

Arun Sanyal, MD, of Virginia Commonwealth University Medical Center in Richmond, Va., and president of the AASLD, remarked that the findings of both groups "are in a very early stage, but they provide proof-of-concept that you can take these extracellular matrices and create functioning artificial livers."

"It's very interesting even though these are emerging technologies," Sanyal added.

Baptista said he can't forecast when these bioartificial organs would be available for use in the general population, though he predicted porcine livers would be good candidates for providing the extracellular matrices for human transplants.

In the meantime, he said the engineered livers could be used for drug discovery and development.

"I hope in the future," Baptista said, "there will be some type of bioengineered livers that will be suitable for transplant."

Baptista and Uygun said they had no disclosures.

The Wake Forest University work was supported by the Portuguese Foundation for Science and Technology.


Primary source: American Association for the Study of Liver Diseases
Source reference:
Baptista PM, et al "The use of whole organ decellularization for the bioengineering of a human vascularized liver" AASLD 2010; Abstract 12.

Additional source: American Association for the Study of Liver Diseases meeting
Source reference:
Uygyn BE, et al "Engineering of a transplantable liver graft" AASLD 2010; Abstract 293.


http://www.medpagetoday.com/MeetingCoverage/AASLD/23073

AASLD:Scientists grow human livers in laboratory

Scientists grow human livers in laboratory


WINSTON-SALEM, N.C. – Saturday, Oct. 30, 2010 – Researchers at the Institute for Regenerative Medicine at Wake Forest University Baptist Medical Center have reached an early, but important, milestone in the quest to grow replacement livers in the lab. They are the first to use human liver cells to successfully engineer miniature livers that function – at least in a laboratory setting – like human livers. The next step is to see if the livers will continue to function after transplantation in an animal model.

The ultimate goal of the research, which will be presented Sunday at the annual meeting of the American Association for the Study of Liver Diseases in Boston and published in an upcoming issue of the journal Hepatology, is to provide a solution to the shortage of donor livers available for patients who need transplants. Laboratory-engineered livers could also be used to test the safety of new drugs.

“We are excited about the possibilities this research represents, but must stress that we’re at an early stage and many technical hurdles must be overcome before it could benefit patients,” said Shay Soker, Ph.D., professor of regenerative medicine and project director. “Not only must we learn how to grow billions of liver cells at one time in order to engineer livers large enough for patients, but we must determine whether these organs are safe to use in patients.”

Pedro Baptista, PharmD, Ph.D., lead author on the study, said the project is the first time that human liver cells have been used to engineer livers in the lab. “Our hope is that once these organs are transplanted, they will maintain and gain function as they continue to develop,” he said.

The engineered livers, which are about an inch in diameter and weigh about .20 ounces, would have to weigh about one pound to meet the minimum needs of the human body, said the scientists. Even at this larger size, the organs wouldn’t be as large as human livers, but would likely provide enough function. Research has shown that human livers functioning at 30 percent of capacity are able to sustain the human body.

To engineer the organs, the scientists used animal livers that were treated with a mild detergent to remove all cells (a process called decellularization), leaving only the collagen “skeleton” or support structure. They then replaced the original cells with two types of human cells: immature liver cells known as progenitors, and endothelial cells that line blood vessels.

The cells were introduced into the liver skeleton through a large vessel that feeds a system of smaller vessels in the liver. This network of vessels remains intact after the decellularization process. The liver was next placed in a bioreactor, special equipment that provides a constant flow of nutrients and oxygen throughout the organ.

After a week in the bioreactor system, the scientists documented the progressive formation of human liver tissue, as well as liver-associated function. They observed widespread cell growth inside the bioengineered organ.

The ability to engineer a liver with animal cells had been demonstrated previously. However, the possibility of generating a functional human liver was still in question.

The researchers said the current study suggests a new approach to whole-organ bioengineering that might prove to be critical not only for treating liver disease, but for growing organs such as the kidney and pancreas. Scientists at the Wake Forest Institute for Regenerative Medicine are working on these projects, as well as many other tissues and organs, and also working to develop cell therapies to restore organ function.

Bioengineered livers could also be useful for evaluating the safety of new drugs. “This would more closely mimic drug metabolism in the human liver, something that can be difficult to reproduce in animal models," said Baptista.

Co-researchers were Dipen Vyas, B.Pharm., M.S., Zhan Wang, M.D., Ph.D. and Anthony Atala, M.D., director of the institute.

http://www.wfubmc.edu/News-Releases/2010/Researchers_Engineer_Miniature_Human_Livers_in_the_Lab.htm

Media Relations Contacts:
Karen Richardson: krchrdsn@wfubmc.edu, 336-716-4453