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Cloning creates stem cell first
4/29/2014 12:53:04 AM
- In two new studies, adult skin cells were used to make embryos
- Stem cells can grow into any kind of tissue
- Many future medical advances are hoped to arise from stem cells
(CNN) -- For the first time, cloning technologies have been used to generate stem cells that are genetically matched to adult patients.
Fear not: No legitimate scientist is in the business of cloning humans. But cloned embryos can be used as a source for stem cells that match a patient and can produce any cell type in that person.
Researchers in two studies published this month have created human embryos for this purpose. Usually an embryo forms when sperm fertilizes egg; in this case, scientists put the nucleus of an adult skin cell inside an egg, and that reconstructed egg went through the initial stages of embryonic development.
"This is a dream that we've had for 15 years or so in the stem cell field," said John Gearhart, director of the Institute for Regenerative Medicine at the University of Pennsylvania. Gearhart first proposed this approach for patient-specific stem cell generation in the 1990s but was not involved in the recent studies.
Stem cells have the potential to develop into any kind of tissue in the human body. From growing organs to treating diabetes, many future medical advances are hoped to arise from stem cells.
Scientists wrote in the journal Cell Stem Cell this month that they used skin cells from a man, 35, and another man, 75, to create stem cells from cloned embryos.
"We reaffirmed that it is possible to produce patient-specific stem cells using a nuclear transfer technology regardless of the patient's age," said co-lead author Young Gie Chung at the CHA Stem Cell Institute in Seoul, South Korea.
On Monday, an independent group led by scientists at the New York Stem Cell Foundation Research Institute published results in Nature using a similar approach. They used skin cells from a 32-year-old woman with Type 1 diabetes to generate stem cells matched to her.
Both new reports follow the groundbreaking research published last year by Shoukhrat Mitalipov and colleagues at Oregon Health & Science University in the journal Cell. In that study, researchers produced cloned embryos and stem cells using skin cells from a fetus and an 8-month-old baby.
"It's a remarkable process that gives us these master cells, these stems cells that are essentially the seeds for all of the tissues in our bodies," said George Daley, director of the Stem Cell Transplantation Program at Boston Children's Hospital, who was not involved in the recent studies. "That's why it's so important for medical research."
A brief history of stem cells
The first developments in the field of stem cell research used leftover embryos created by the union of sperm and egg from in vitro fertilization.
But embryonic stem cell research is controversial because to use the stem cells for developing medical treatments, the embryo is destroyed. Embryos have the potential to develop into a fully formed human, bringing up ethical questions.
Scientists later realized that it's not necessary to use embryos to obtain stem cells that match patients. Shinya Yamanaka won the 2012 Nobel Prize for Physiology or Medicine for discovering how to make "induced pluripotent stem cells," or IPS cells.
IPS cells are made by inserting genes to "turn back the clock" on mature cells that already have specific functions. It doesn't matter what the cell was before; it can now be reprogrammed as any kind of cell researchers want.
Why, then, would researchers bother to make stem cells using cloning, which requires human eggs and the creation of embryos?
"People have made patient-matched stem cells using IPS methods," said Dieter Egli, senior author on the Nature paper that could have implications for diabetes treatment and researcher at the New York Stem Cell Foundation. "But it is not clear in the U.S. at the very least, and also elsewhere, how and if these are going to be translated into people."
Egli points out that there have been some reports that IPS cells may have shortcomings when converted into specific cell types, and that stem cells produced by cloning may be better.
But which stem cell type is better and safer -- the IPS cells or cells from cloned embryos? That is still an open question. To settle it, there would need to be a comparison of the two stem cell types generated using the DNA of the same person.
Gearhart doesn't see the cloning method replacing the use of IPS cells, which are not controversial and don't require that women donate their eggs.
"As we learn more about the reprogramming process that normally occurs in the egg following fertilization, we can use that information to produce better IPS cells," Gearhart said.
The process of extracting eggs is complex and expensive; having enough supply is a "serious concern," Daley said.
"The more we learn about reprogramming, the more I think IPS will be the one of choice," Gearhart said.
Making stem cells by cloning
An embryo, the earliest stage of human development, is a cluster of cells smaller than the period at the end of this sentence.
To make a cloned embryo, scientists use equipment analogous to "like a half-million-dollar video game," Daley said.
Researchers perform surgery on eggs with needles that are the 10th of the size of a human hair. They use joysticks to manipulate the tiny equipment, spearing the egg, removing its DNA and then transferring the nucleus of a skin cell into the egg.
"That process, which is called nuclear transfer, sets in motion this remarkable process of early human development," Daley said. "We trick this reconstructed egg into thinking it's been fertilized."
Chung's group -- which led the Cell Stem Cell study -- used this cloning method that Mitalipov had pioneered to get two stem cell lines out of 77 eggs. "It seems that the quality of oocyte (egg) plays a pivotal role," Chung said.
Egli and colleagues had their own spin on the cloning process, amending it so that it happens in a more controlled way. Their study in Nature used electricity in combination with chemicals, and manipulating the calcium concentration, to improve the procedure. They generated stem cells specific to the diabetic patient who had donated skin cells; the eggs came from donors.
This group got four cell lines from 71 eggs, said research assistant Lydia Mailander. The average egg donation is 14 to 15 oocytes. Researchers estimate it would take two such donations to get one stem cell line.
In mice, Egli and colleagues showed in a separate study that the cloned stem cells from the diabetic patient mature into glucose-responsive beta cells, which secrete insulin into the bloodstream of the animals.
Further considerations
It's not clear that there are enough eggs in supply to support a large-scale production of stem cells this way, experts said.
For the near-term research purposes, there seem to be enough eggs available for stem cell cloning: About 10,000 egg donor cycles occur annually in the United States, Egli said.
But egg donation for research is generally low, Gearhart said. According to the American Diabetes Association, about 1 million Americans have Type 1 diabetes, the target population for a potential stem cell therapy.
The cloning method takes a few weeks, and is not significantly faster than generating IPS cells, Egli said.
Including compensation to the woman, an egg donation cycle costs about $14,000, Egli said.
"It may not at all be more expensive (than IPS) if the cells that we make are actually better," he said. "That's why it's important to do these comparisons."
Such a comparison would be interesting, said Daley, but the advantages would have to be considerable to beat out IPS, which is "much more efficient and less ethically contentious that Yamanaka (the Nobel winner) taught us."
Still, from a research perspective, the cloning method could help scientists interested in understanding how an egg reprograms the cell, Daley said. It could help answer: "How does an egg reset the whole identity of an adult cell back to an embryonic state?"
Stem cell cloning research might, in this way, teach scientists how to make stem cells more efficiently, he said, and optimize them for medical applications.
We love to hear from our audience. Follow @CNNHealth on Twitter and Facebook for the latest health news and let us know what we're missing.
How about making a clone?
Mitalipov told CNN in 2013 that the embryos created in his study, from skin cells and eggs, would not grow babies. That would have required additional technology, and it wasn't part of the study.
But the same basic "nuclear transfer" principle used in Mitalipov's, Chung's and Egli's studies was used create Dolly the sheep, the first mammal clone.
In Dolly's case, an embryo created by nuclear transfer was transplanted to a ewe, which gave birth to a sheep.
In the case of human embryos generated in these stem cell experiments, "it would be dangerous and unethical to attempt to transfer them into a uterus," Daley said.
Follow Elizabeth Landau on Twitter at @lizlandau
Sponsors dump race row NBA team
4/29/2014 1:50:39 AM
- NEW: Players hope Donald Sterling will have to give up Los Angeles Clippers
- NEW: Opposing NBA coach calls for Clippers fans to boycott playoff game Tuesday
- NBA commissioner will speak about investigation on Tuesday
- State Farm, airline Virgin America cut ties to the L.A. Clippers
(CNN) -- When Commissioner Adam Silver speaks to the media Tuesday about the NBA's findings in the investigation into racist remarks attributed to Clippers owner Donald Sterling, the league's players hope it includes the most severe penalties.
"When a hint of cancer is shown, you have to cut it out immediately, and I feel that's where the players are today," Kevin Johnson, the former all-star who is the chairman of the National Basketball Players Association's executive committee, told CNN's "Erin Burnett OutFront."
Johnson said the players trust that the new commissioner, on the job for less than three months, will find the right penalties for Sterling, who has owned the Clippers for almost 30 years.
"They don't think he's worthy to be an owner," said Johnson, also the mayor of Sacramento, "so whether there's a sanction that includes a suspension, whether there's a sanction that includes a hefty fine ... the players feel very strongly that he's not fit to be an owner and a part of this NBA family."
The NBA has scheduled a news conference for 2 p.m. ET Tuesday.
Monday brought a slew of sponsors distancing themselves from the team and a host of other owners and team officials condemning the comments attributed to Sterling, who has never been disciplined by the league.
On Saturday, the website TMZ posted a 10-minute recording of a conversation, reportedly between Sterling and his girlfriend, whose legal name is V. Stiviano. According to the website, the conversation occurred on April 9.
On the recording, the man and woman argue about photos posted to Instagram in which she appears with African-Americans. The man says he doesn't want the woman bringing any black people to games with her.
Sterling has not commented publicly on the scandal. Team President Andy Roeser issued a statement this weekend that said "what is reflected on that recording is not consistent with, nor does it reflect (Sterling's) views, beliefs or feelings." He suggested that the recording was an attempt by Stiviano to "get even" with Sterling.
Speculation on possible punitive actions
Silver has promised the league would give Sterling due process but would act quickly.
It is unclear whether Silver could order Sterling to sell the Clippers, a team he bought for $12 million in 1981 and is now worth $575 million, according to Forbes magazine. A lifetime suspension and fine of at least $1 million is more likely, experts say.
The commissioner might announce an indefinite suspension while the investigation continues, CNN's Rachel Nichols reported.
Opinion: Sterling has to go
"He (eventually) could suspend Donald Sterling maybe for a year, maybe even two years or even indefinitely," Nichols said. "And the idea and the hope would be that if he made him so uncomfortable, if he was removed from day-to-day operations, if sponsors are pulling out the way that they are, there would be some way to convince Sterling, it's in your best interest and the interest of everyone else to sell the team."
Nichols likened the situation to the late Marge Schott, who owned the Cincinnati Reds and made racist and other insensitive comments. She was suspended twice, the second time in 1996, and sold the team in 1999.
Other NBA owners have called the remarks attributed to Sterling "abhorrent," "reprehensible," "hurtful," and said they have no place in the league or anywhere in society.
And they all said they have confidence Silver will handle the matter well.
Charlotte Bobcats owner and Hall of Fame Michael Jordan made a rare public statement on a controversial subject.
"As an owner, I'm obviously disgusted that a fellow team owner could hold such sickening and offensive views," he said. "As a former player, I'm completely outraged. There is no room in the NBA -- or anywhere else -- for the kind of racism and hatred that Mr. Sterling allegedly expressed."
Five key players in the Donald Sterling uproar
TMZ posts audio recording
In the recording, the man seems mad about a photo the woman posted to Instagram with Magic Johnson, now a part owner of the Los Angeles Dodgers.
"In your lousy f**ing Instagrams, you don't have to have yourself with -- walking with black people," the man says.
"If it's white people, it's OK?" she responds. "If it was Larry Bird, would it make a difference?"
Bird was Johnson's chief rival when Bird's Celtics and Johnson's Lakers ruled the NBA.
"I've known (Magic Johnson) well, and he should be admired. ... I'm just saying that it's too bad you can't admire him privately," the man on the recording says. "Admire him, bring him here, feed him, f**k him, but don't put (Magic) on an Instagram for the world to have to see so they have to call me. And don't bring him to my games."
On Sunday, the sports website Deadspin posted five additional minutes it said was part of the same audio recording.
Neither website has said how it obtained the recordings.
Stiviano's lawyer's office said Sunday that she didn't release the recordings to TMZ but that they are legitimate.
"This office understands that the currently released audio tape of approximately 15 minutes is a portion of approximately one (1) hour of overall audio recording of Mr. Donald T. Sterling and Ms. Stiviano, and is in fact legitimate," Mac E. Nehoray said in a news release. "Ms. Stiviano did not release the tape(s) to any news media."
Sterling has history of fighting discrimination claims in court
Clippers considered boycott
Sterling's wife, who is suing the woman, gave CNN affiliate KABC a statement Sunday night.
"Our family is devastated by the racist comments made by my estranged husband," Rochelle Sterling said. "My children and I do not share these despicable views or prejudices. We will not let one man's small-mindedness poison the spirit of the fans and accomplishments of the team in the city we love."
Los Angeles Clippers coach Doc Rivers told reporters Monday that he was offered an opportunity to speak to Sterling after the comments attributed to the team's owner were posted online, but Rivers said he "passed." Rivers added, "I don't think right now is the time or place, for me at least. And so I just took a pass."
The coach, in his first year with the Clippers, said he believes that Sterling did make the comments but said he wanted to find out if the recording was doctored.
Rivers confirmed the team's players had talked about boycotting a playoff game but decided against it. Whether the coach or a player will address the fans before Tuesday's Game 5 against the Golden State Warriors is being discussed internally, Rivers said. The teams each have two wins in the best-of-seven-games series.
Golden State coach Mark Jackson said Monday that fans should make a statement by staying home.
Poll: Do you think Clippers players should boycott?
Sponsors leave in droves
Twelve Clippers sponsors have taken action. State Farm, Virgin America, CarMax, Red Bull were among companies to pull sponsorships, at least temporarily, CNN Money reported.
Sterling was to receive a lifetime achievement award at an event next month to mark the 100th anniversary of the Los Angeles NAACP, but the national organization said Monday that would not happen.
Sterling had been given a lifetime achievement award from the organization in 2009, according to a brochure obtained by CNN.
Roeser, the Clippers' president, suggested Saturday that Stiviano -- whom he didn't mention by name -- was "getting even" with Sterling over a lawsuit.
Rochelle Sterling filed a lawsuit last month against Stiviano, who she said was having an affair with her husband.
In the complaint, Rochelle Sterling accuses Stiviano of targeting extremely wealthy older men. The suit claims that Donald Sterling used the couple's money to buy Stiviano a Ferrari, two Bentleys and a Range Rover and that Stiviano took possession of a $1.8 million duplex through fraud. Sterling also gave her nearly $250,000 in cash, the court document says.
Stiviano countered in another court document that there was nothing wrong with Donald Sterling giving her gifts and that she never took advantage of the Clippers owner, who made much of his fortune in real estate.
Speaking about the recording, Roeser said, "We do not know if it is legitimate or it has been altered. We do know that the woman on the tape -- who we believe released it to TMZ -- is the defendant in a lawsuit brought by the Sterling family alleging that she embezzled more than $1.8 million, who told Mr. Sterling that she would 'get even.' "
Will the NBA make Sterling the first owner to give up team?
Reaction: 'Disturbing and offensive'
CNN's Paul Vercammen, Ashley Fantz, Stephanie Elam, Ralph Ellis, AnneClaire Stapleton, Joe Sutton, Wayne Sterling and Kevin Dotson contributed to this report.
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