Researchers seek 'safety lock' against tumor growth after stem cell transplantation

PUBLIC RELEASE DATE:

6-Aug-2014

Contact: Robert Miranda cogcomm@aol.com Cell Transplantation Center of Excellence for Aging and Brain Repair

Putnam Valley, NY. (Aug. 6, 2014) Recent studies have shown that transplanting induced pluripotent stem cell-derived neural stem cells (iPS-NSCs) can promote functional recovery after spinal cord injury in rodents and non-human primates. However, a serious drawback to the transplantation of iPS-NSCs is the potential for tumor growth, or tumorogenesis, post-transplantation.

In an effort to better understand this risk and find ways to prevent it, a team of Japanese researchers has completed a study in which they transplanted a human glioblastoma cell line into the intact spinal columns of laboratory mice that were either immunodeficient or immunocompetent and treated with or without immunosuppresant drugs. Bioluminescent imaging was used to track the transplanted cells as they were manipulated by immunorejection.

The researchers found that the withdrawal of immunosuppressant drugs eliminated tumor growth and, in effect, created a 'safety lock' against tumor formation as an adverse outcome of cell transplantation. They also confirmed that withdrawal of immunosuppression led to rejection of tumors formed by transplantation of induced pluripotent stem cell derived neural stem/progenitor cells (iPS-NP/SCs).

Although the central nervous system has shown difficulty in regenerating after damage, transplanting neural stem/progenitor cells (NS/PCs) has shown promise. Yet the problem of tumorogenesis, and increases in teratomas and gliomas after transplantation has been a serious problem. However, this study provides a provisional link to immune therapy that accompanies cell transplantation and the possibility that inducing immunorejection may work to reduce the likelihood of tumorogenesis occurring.

"Our findings suggest that it is possible to induce immunorejection of any type of foreign-grafted tumor cells by immunomodulation," said study co-author Dr. Masaya Nakamura of the Keio University School of Medicine. "However, the tumorogenic mechanisms of induced pluripotent neural stem/progenitor cells (iPS-NS/PCs) are still to be elucidated, and there may be differences between iPS-NS/PCs derived tumors and glioblastoma arising from genetic mutations, abnormal epigenetic modifications and altered cell metabolisms."

The researchers concluded that their model might be a reliable tool to target human spinal cord tumors in preclinical studies and also useful for studying the therapeutic effect of anticancer drugs against malignant tumors.

"This study provides evidence that the use of, and subsequent removal of, immunosuppression can be used to modulate cell survival and potentially remove tumor formation by transplanted glioma cells and provides preliminary data that the same is true for iPS-NS/PCs." said Dr. Paul Sanberg, distinguished professor at the Center of Excellence for Aging and Brain Repair, University of South Florida. "Further study is required to determine if this technique could be used under all circumstances where transplantation of cells can result in tumor formation and its reliability in other organisms and paradigms."

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Researchers seek 'safety lock' against tumor growth after stem cell transplantation

Star Scientist Embroiled in Controversy Found Dead in Apparent Suicide

The stem-cell research community reels after Yoshiki Sasai, a famous name in regenerative medicine, is found dead on August 5

Yoshiki Sasai. Credit: Nick Higgins

Scientists around the world are struggling to get to grips with the loss of one of the brightest stars in stem-cell science. Yoshiki Sasai of the RIKEN Center for Developmental Biology (CDB) in Kobe brought excitement and rigour to the field but died yesteday, August 5, aged 52. The reasons for Sasais apparent suicide are still not clear but a scandal swirling about two stem-cell papers published inNaturein January had wreaked havoc on his career.

Dr. Sasai was a rigorous and innovative scientist and his loss will be deeply felt, saysJanet Rossantat the Hospital for Sick Children in Toronto, Canada, a former head of the International Society for Stem Cell Research. His most important contributions to the stem-cell field came from his background in developmental biology.

Sasais research spanned developmental biology, stem cells, organogenesis and tissue engineering. His success was built on his painstaking efforts to understand exactly which factors needed to be added or removed to cell cultures to guide embryonic stem cells as they differentiated to mature cell types,especially neuronal cells.

He sees things that others dont see,Eddy De Robertistold Naturein a 2012 interview. De Robertis, a developmental biologist at the University of California, Los Angeles, who supervised Sasais postdoctoral work in the mid 1990s, recalled Sasai once retyping a manuscript lost in a computer from memory with word-for-word perfection. Id never seen anything like that, he said.

Lab-grown cortex One of Sasais innovations was thediscovery in 2007of a pharmacological compound that kept embryonic stem cells from dying when separated from each other. Previously, embryonic stem cells had to be manually cut with a cumbersome method and transferred as partial colonies, which resulted in experimental variation. His paper solved that overnight, saysLuc Leynsof the Vrije Universiteit in Brussels.

But Sasai's show-stoppers came shortly after that. Based on his success in differentiating neurons, Sasai started mimicking embryonic development with such fidelity that his cells would organize themselves into three-dimensional structures, including agoblet-shaped clump of retinal tissue known as an optic cupandintricate layers of tissue that resembled a cerebral cortex.

Both these discoveriesopened the field ofin vitrobrain organogenesis. Finally, we have easy access to the developing brain without having to micro dissect embryos, says Leyns. Leyns says he uses Sasais papers to show masters students how a modern scientific discovery is made and progressively built-up to a climax.

Sasais work was inspirational, says Pete Coffey of University College London, where Sasai presented the optical cup research last November. The clarity of his presentation, the excitement and post lecture discussions with fellows and students are still discussed today. He had a major impact on my group, says Coffey. Sasais research will probably contribute to treatments for various disorders, such as macular degeneration. His findings galvanized the ophthalmology community in truly developing a cell therapy for blinding disorders, says Coffey.

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Star Scientist Embroiled in Controversy Found Dead in Apparent Suicide

Yoshiki Sasai Suicide: Japanese Stem Cell Scientist Found Dead In Kobe Facility

A Japanese scientist who was among a team of researchers accused of falsifying the results of two stem cell studies committed suicide Tuesday at a government science institute in western Japan. Yoshiki Sasai, deputy director of the Riken Center for Developmental Biology, was found by a security guard at the Kobe facility with a rope around his neck, the Associated Press reports. Authorities said he had suffered from cardiac arrest and was pronounced dead two hours later.

Sasai, 52, was considered an expert in embryonic stem cell research and co-authored two research papers published in January in the journal Nature that detailed a seemingly groundbreaking method of harvesting stem cells to grow new human tissue. Sasai and lead author Haruko Obokata reported having successfully altered ordinary mouse cells into versatile stem cells by immersing them in a mildly acidic solution. The resulting cells were named stimulus-triggered acquisition of pluripotency (STAP) cells.

The studies were initially praised as being on the cutting edge of stem cell treatment, but were quickly disputed when other scientists could not replicate the experimental procedure. The papers were retracted six months later after the journal found they contained erroneous data, among other flaws.

Scientists at RIKEN Center for Developmental Biology in Kobe are deeply concerned about the allegations regarding the recently reported STAP cells, the center said in a statement released in March. We wish to express our strong commitment to maintaining the highest level of scientific integrity to the public and the scientific community. We are fully aware that trust from the society is crucial for research activities carried out in RIKEN.

The scandal apparently affected Sasais health. Following the initial revelation that the research he was involved in may have been flubbed, he was hospitalized in March for stress, according to Riken spokesman Satoru Kagaya, who told reporters during a televised news conference on Tuesday that Sasai "seemed completely exhausted" when they talked over the phone in May.

Several suicide notes were found on Sasais secretarys desk, according to the Wall Street Journal. The content of the notes has not been made public, but officials said two of the notes were addressed to Riken officials, one of whom was Obokata.

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Yoshiki Sasai Suicide: Japanese Stem Cell Scientist Found Dead In Kobe Facility

Embryonic Stem-Cell Research: Experts Debate Pros and Cons

Experts debate embryonic stem-cell research. What are the pros and cons? Is it necessary? Is it ethical? Get the facts and learn the issues from the experts themselves.

The positions couldnt be more polar.

Some say it could save lives. Others say it kills them. And the embryonic stem-cell research debate shows no signs of dying down any time soon.

We invited each participant to write an argument, then read the opponents argument and write a rebuttal. Neither was allowed to read the others initial argument before writing his own, and neither could read the others response before rebutting.

Opponents point out that research on adult stem cells has yielded more practical results so farfor example, bone marrow transplants. But proponents believe embryonic stem cells hold more promise. Besides, they say, research on adult stem cells has been going on longer than on embryonic ones.

In the end, whatever such cells may or may not be able to give us, the question comes down to: Is embryonic stem-cell research ethical? And thats what we asked our experts to debate.

Share your opinions in the comments section at the end of the article.

Human embryonic stem-cell research is not only ethical, it is an essential field to pursue to make key advances in biomedical research to treat diseases effectively where there are currently no curesincluding, but not limited to, paralysis from spinal cord injury, diabetes, Parkinsons disease and cancer.

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Embryonic Stem-Cell Research: Experts Debate Pros and Cons

Quebec womans leukemia battle highlights need for minority bone marrow and stem cell donors

MONTREALA Quebec womans desperate online plea for a compatible stem-cell donor in her bid to fight cancer a second time is shedding light on the lack of minorities on official lists in Canada and abroad.

Mai Duong finds herself battling leukemia again and doctors say they would like to proceed with a transplant of bone marrow or cord blood stem cells within a month.

But Duong, 34, has discovered that locating the right person can be a needle-in-a-haystack challenge, particularly for those who are from a non-Caucasian background.

This is a global problem, Duong, who is of Vietnamese origin, said in an interview from her room at Montreals Maisonneuve-Rosemont Hospital.

We cant do a scavenger hunt every time someone has this type of problem.

Duong, who returned home a few days after being interviewed, said a recent bone marrow biopsy showed no signs of cancer. She will now begin four weeks of maintenance chemotherapy, which is given in lower doses to assist in prolonging a remission.

The mother of a 4-year-old girl, Duong successfully fought off acute leukemia in 2013 with chemotherapy. She had to terminate a 15-week pregnancy to undergo the treatment. Duong was in remission until a blood test revealed leukemia had returned this past May.

Seventy per cent of people who had that type of leukemia were just cured with chemotherapy, and unfortunately Im in the 30 per cent, she said.

The diagnosis and a lack of a match in her family have touched off a mad scramble to find a fellow Vietnamese donor. An online campaign has taken that hunt global.

I have cancer, I had a relapse, I dont have a bone marrow (donor) these are things I cannot change, Duong said. So I said, what can I do about it?

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Quebec womans leukemia battle highlights need for minority bone marrow and stem cell donors

Disgraced Japanese stem cell scientist found dead

Suspected suicide: Yoshiki Sasai in April. Photo: AFP

Tokyo: A renowned Japanese stem cell scientist who co-wrote research that was later retracted in an embarrassing scandal has been found dead, police say.

The body of Yoshiki Sasai, 52, was discovered hanging inside the stairwell of a building that houses the Riken Centre for Developmental Biology, one of the country's most prestigious scientific research institutions.

The office is in the western city of Kobe.

Haruko Obokata, who was mentored by Yoshiki Sasai. Dr Obokata's research on stem cells published in Nature was found to have been falsified. Photo: AP/Kyodo News

"Yoshiki Sasai was discovered hanging on Tuesday morning inside one of Riken's research buildings and, after being sent to hospital, he was confirmed dead at 11.03am," a spokesman for the Hyogo Prefectural police said.

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"Police are investigating the case as a suspected suicide."

He added that authorities discovered "farewell notes" that Dr Sasai had left behind, with public broadcaster NHK reporting that one was left for Haruko Obokata.

Dr Sasai mentored Dr Obokata, whose study earlier this year was hailed as a "game-changer" in the quest to grow transplant tissue in the laboratory.

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Disgraced Japanese stem cell scientist found dead

Bong Revilla Jr. at Jinggoy Estrada, naalarma sa nangyari kay Lolit Solis

USAPANG CELL at stem cell.

Kuwento ito mismo ni Lolit Solis tungkol sa kanyang ikalawang stem cell treatment sa Germany kamakailan, kasamang muli ang alagang si Lorna Tolentino.

Like the first stem cell treatment she underwent more than a year ago, hindi ikinakailamuch less ikinahihiyani Nay Lolit na amining courtesy of her friend Dra. Vicki Belo ang milyong piso ring halaga ng nasabing medical breakthrough.

Malaki ang iginanda ng kundisyong pisikal ng talent manager-TV host makaraan ng unang gamutan. Mas gumaan daw ang kanyang pakiramdam.

But her diabetesthat manifested when she turned more than 60became burdensome sa puntong kinailangan na niyang mag-insulin. Ito ang itinuturong culprit ni Nay Lolit kung bakit bagamat matagumpay naman ang kanyang ikalawang stem cell treatment ay nawalan siya raw ng malay nang makauwi nat nagpapahinga sa kanyang West Fairview residence.

Dahil naalarma ang kanyang mga kaibigan most specially in showbiz, there was a seemingly endless barrage of phone calls after she regained her consciousness.

A concerned Bong Revillaalso her wardrang her up. Tanong daw nang tanong ang senador kung anong nangyari kay Nay Lolit at kung ano ang kailangan nito.

Moments later, ang nasa kabilang linya naman daw ng telepono ay si Jinggoy Estrada, na noong malamang libre lang naman ang naturang treatment ay ito pa raw ang nanita sa kanya na may halo namang malasakit, Eh, kasi naman, ang hilig-hilig mo sa libre, no! Hayan tuloy nangyari sa yo!

Realizing that Senator Jinggoy had a point, tumawa na lang daw si Nay Lolit.

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Bong Revilla Jr. at Jinggoy Estrada, naalarma sa nangyari kay Lolit Solis

Japanese scientist dies by suicide after stem-cell research scandal

A Japanese researcher at the centre of discredited research that was initially hailed as a potential breakthrough for stem-cell treatment, killed himself after months of stress and exhaustion, officials said on Tuesday.

Yoshiki Sasai, co-author of the high-profile research that had seemed to offer hope for replacing damaged cells or even growing new human organs, was found early on Tuesday at the Riken institute where he worked in Kobe, western Japan, police and the institute said.

It is confirmed as a suicide, said a police spokesman. It was a hanging.

Sasai, 52, had been hospitalized in March for stress and become less receptive to media inquiries during the controversy over the teams research, said Riken spokesman Satoru Kagaya.

The scientist had seemed completely exhausted in their last phone conversation around May or June, Kagaya told a televised news conference.

As deputy director of Rikens Center for Developmental Biology, Sasai supervised the work of lead author Haruko Obokata, which took the world of molecular biology by storm when it was published in the British journal Nature in January.

It was retracted after months of controversy that made front-page news in Japan and tarnished the countrys reputation for scientific research.

The journals editor-in-chief, Phil Campbell, issued a statement in London describing Sasais death as a true tragedy for science and an immense loss to the research community.

Yoshiki Sasai was an exceptional scientist and he has left an extraordinary legacy of pioneering work across many fields within stem cell and developmental biology, Campbell said.

It is very unfortunate that this happened, said the governments top spokesman, Chief Cabinet Secretary Yoshihide Suga. Mr Sasai contributed greatly in the field of developmental biology and was an internationally renowned researcher.

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Japanese scientist dies by suicide after stem-cell research scandal

Japanese scientist stem-cell scientist Yoshiki Sasai commits suicide

Yoshiki Sasai, who was embroiled in a stem-cell scandal, committed suicide He was found with a rope around his neck at science institute Riken in Japan Mr Sasai, 52, was deputy chief of Riken's Center for Developmental Biology He co-authored stem-cell research papers with falsified contents

By Ted Thornhill

Published: 06:20 EST, 5 August 2014 | Updated: 09:29 EST, 5 August 2014

A senior Japanese scientist embroiled in a stem-cell research scandal died on Tuesday in an apparent suicide, police said.

Yoshiki Sasai, who supervised and co-authored stem-cell research papers that had to be retracted due to falsified contents, was found suffering from cardiac arrest at the government-affiliated science institute Riken in Kobe, in western Japan, according to Hyogo prefectural police.

Sasai, 52, was deputy chief of Riken's Center for Developmental Biology.

Tragic:Yoshiki Sasai, who was embroiled in a stem-cell scandal, committed suicide and was found with a rope around his neck at his place of work

A security guard found him with a rope around his neck, according to Riken. Sasai was rushed to a hospital, but was pronounced dead two hours later.

Police and Riken said Sasai left what appeared to be suicide notes, but refused to disclose their contents.

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Japanese scientist stem-cell scientist Yoshiki Sasai commits suicide

Maamba resident awarded Harvard Stem cell institute internship

Yanick Mulumba

Kabungo Yanick Mulumba, a resident of Maamba, Zambia, a graduate of St. Canisius High School, and now a senior at Harvard University in Cambridge, Massachusetts, USA, is one of forty undergraduate students accepted into the 2014 Harvard Stem Cell Institute (HSCI) Internship Program, which provides participants with a challenging summer research experience in a cutting-edge stem cell science laboratory.

Mulumba is spending ten weeks, from June 9 to August 15, in the Harvard University Department of Stem Cell and Regenerative Biology laboratory of HSCI Principal Faculty member Chad Cowan, PhD, known for his research on genetic disease modeling. Mulumbas project this summer is to engineer transplantable white blood cells that dont attack the bodys own cells when used for adoptive immunotherapya treatment that uses biological substances to boost a patients immune system.

The internship has enhanced my critical thinking through troubleshooting and planning of experiments, Mulumba said. Ive also been exposed to leaders in academia and industry who have helped me learn how to combine my interests in medicine, research, and healthcare management.

Over the course of the program, interns participate in a stem cell seminar series, a career pathways presentation, and a weekly stem cell companion course. They present their summer research findings, both orally and in poster format, at an end-of-program symposium.

This program represents an exciting opportunity for undergraduates to gain hands-on experience in stem cell research while working in an HSCI laboratory under the supervision of an experienced researcher, said HSCI Internship Program co-director M. William Lensch, PhD.

The Harvard Stem Cell Institute gratefully acknowledges the generous support of the following sponsors for the 2014 HSCI Internship Program: Biogen Idec, Boehringer Ingelheim Pharmaceuticals Inc., EPSRC Centre for Innovative Manufacturing in Regenerative Medicine, Loughborough University (UK), Novartis Institutes for BioMedical Research, and Vertex Pharmaceuticals.

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Maamba resident awarded Harvard Stem cell institute internship