「凍物園」研發幹細胞分化精卵 可望避免物種滅絕 | 環境資訊中心
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「凍物園」研發幹細胞分化精卵 可望避免物種滅絕

2011年09月19日
摘譯自2011年9月7日ENS美國,加州,拉荷雅報導;林可麗編譯;洪美惠審校

遺傳學家萊德(Oliver Ryder)展示他的冷凍動物園所蒐集的標本。圖片來自:聖地牙哥動物園。美國加州斯克雷普斯研究所(Scripps Research Institute)的科學家們由瀕危物種的正常皮膚細胞作為起始點,首次替這些物種製造出幹細胞。他們表示,這些幹細胞也許可改善某些瀕危物種的生殖與遺傳學的多元性,甚至可能拯救他們免於遭受滅絕。幹細胞也可能改善圈養的瀕危物種健康狀態。

在生命的初期以及成長過程,幹細胞具有發展成體內許多不同種類細胞型態的潛力。在許多組織中,幹細胞是內部的修復系統,只要人體或是動物還活著,就可無止境地進行細胞分裂,以替其他的細胞補充更新。

當一個幹細胞分裂時,每個新的細胞將可能保持在幹細胞的狀態,或是分化為另一種具有特定功能的細胞類型,例如肌肉細胞、紅血球細胞、大腦細胞、卵子或精子。

萊德博士是聖地牙哥動物園保育研究所所長,當在他與斯克雷普斯研究所的發展神經生物學教授蘿鈴(Jeanne Loring)博士進行聯繫,以便討論瀕危物種幹細胞的採集事宜時,他已經建立了「凍物園」(Frozen Zoo),當時他的「凍物園」裡儲存了超過800個物種的皮膚細胞與其他生物材料的貯存庫。

萊德博士認為,瀕危物種的幹細胞也許可以開發出足以拯救生命的醫學療法,或藉由新的繁殖方式保存或拓展遺傳多元性的潛力。

當蘿鈴的工作團隊在2008年初跟萊德見面時,他們了解到,將正常成人細胞轉化成幹細胞的新穎科技也許可能運用在瀕危物種上。

稱作「誘導式多功能」(induced pluripotency)的技術,是科學家藉由將基因植入正常細胞中,將正常細胞轉化為幹細胞的機制。

萊德建議由兩項物種展開這項工作。

芝加哥林肯公園動物園的鬼狒。圖片節錄自:Thomas Kost相本。

第一個物種是靈長類動物,俗稱鬼狒(drill)或灰狒狒(Mandrillus leucophaeus),鬼狒是一種與狒狒跟西非大猴(mandrill)血緣相近的猴子。鬼狒因雨林棲息地受到砍伐而迫離家園,是非洲最嚴重瀕絕哺乳動物之一。

在野外,鬼狒只能在奈及利亞的十字河州(Cross River State)、喀麥隆(Cameroon)、西非比奧柯島(Bioko Island),以及赤道幾內亞的部分區域發現。

萊德選擇鬼狒的原因是因為它與人類的遺傳特性相似,而且因為圈養的動物經常受糖尿病症所擾,研究學者正致力於以幹細胞療法來治療人類的糖尿病。

聖地牙哥動物園野生公園中的北非白犀牛。圖片來自:聖地牙哥動物園。北非白犀牛(Ceratotherium simum cottoni)則是第二順位。萊德選擇它的原因是因為北非白犀牛跟靈長類動物遺傳基因差距大,而且它是全球最嚴重瀕絕的動物之一。目前全球僅剩下7隻,全部都受到圈養,其中兩隻在聖地牙哥動物園野生公園裡。

北非白犀牛主要分布於烏干達西北部、查德南部、南蘇丹的南部、中非共和國的東部,以及剛果共和國的東北部。在1970年代與1980年代間,盜獵者把北非白犀牛的數量自500隻降低到15隻。最後一批存活下來的野生北非白犀牛原本居住在剛果的加蘭巴國家公園。原先在2005年將這批野生北非白犀牛遷移到肯亞禁獵區的計畫,則因為盜獵者趕盡殺絕的悲劇下未曾付諸實現。

萊德表示,「管理瀕危物種最好的方式就是禁獵物種與保護棲息地,但並不一定有用。」

萊德說,「幹細胞科技提供了某些程度的希望,即使動物已經被趕出野生的棲息地,這些動物仍可能得以免於受滅絕,我認為如果人類想要拯救這個物種,我們必須發展新的方法。」

對於如北非白犀牛這樣小的族群數目物種而言,最值得憂心的事情就是,即便牠們繁殖,它們的遺傳多樣性低將是無可避免的命運,而北非白犀牛已經多年沒有繁殖的現象了。況且,這樣的近親繁殖將導致下一代不健康。

在實驗室裡反覆嘗試多年後,研究學者發現在人類體內具有誘導式多功能的基因,對鬼狒與犀牛也具有相同的作用。研究學者因此得以開始建立一個新的動物園,也就是幹細胞動物園。

研究學者現在正朝誘導幹細胞分化為精子或卵子細胞的方向努力。

一旦能夠成功誘導幹細胞分化為精子或卵子細胞,科學家們也許將能夠把凍物園中保存的絕種動物皮膚細胞轉變為幹細胞,再觸發其分化機制,將幹細胞轉化為精子細胞。然後,再將這些精子細胞與活體動物的卵子透過體外授精結合。

藉由這樣的方式,將能再把遺傳多元性重新引入現有的族群中,讓動物族群更健康,數量更多,並且發展更為健全。

科學家表示,另一種方法是利用幹細胞製造出精子與卵子,將其授精結合後的胚胎植入活體動物中。現有的研究發展認為這樣的過程將比目前的複製科技更為可靠。

蘿鈴表示,研究小組希望能夠藉由製造瀕危物種的幹細胞,來擴充他們的幹細胞動物園。

這些研究學者目前正致力於尋找經費來源來資助這條嶄新的研究路線。

其他的科學家正在研究由幹細胞製造精子與卵子的可能性,以作為人類不孕症的潛在解決方案。蘿鈴希望一些研究人員可以考慮在先期的技術發展階段利用瀕危物種的幹細胞進行試驗。

她表示,「我認為道德上而言,對瀕危物種進行實驗會比對人類實驗更容易進行。我也懷疑在這個領域的研究者會想要利用人類的細胞來進行實驗。」

這篇研究論文在2011年9月4日於「自然方法」(Nature Methods)期刊中發表。

Stem Cells of Endangered Species Could Stave Off Extinction
LA JOLLA, California, September 7, 2011 (ENS)

Starting with normal skin cells from endangered species, scientists with The Scripps Research Institute have for the first time produced stem cells from these species. They say such cells could improve reproduction and genetic diversity for some endangered species, possibly saving them from extinction. Stem cells also could improve the health of endangered animals in captivity.

Stem cells have the potential to develop into many different cell types in the body during early life and growth. In many tissues they serve as an internal repair system, dividing without limit to replenish other cells as long as the person or animal is still alive.

When a stem cell divides, each new cell has the potential either to remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, a brain cell, an egg or a sperm.

Oliver Ryder, PhD, the director of genetics at the San Diego Zoo Institute for Conservation Research, had already established the Frozen Zoo, a bank of skin cells and other materials from more than 800 species when he contacted Jeanne Loring, PhD, professor of developmental neurobiology at Scripps Research to discuss collecting stem cells from endangered species.

Dr. Ryder thought stem cells from endangered species might enable lifesaving medical therapies or offer the potential to preserve or expand genetic diversity by offering new reproduction possibilities.

When Loring's team met with Ryder in early 2008, they realized that a new technique that turns normal adult cells into stem cells might work for endangered species.

Called "induced pluripotency," the technique works when scientists insert genes into normal cells that transform them into stem cells.

Ryder suggested two species to begin the work.

The first is a primate called a drill, Mandrillus leucophaeus, a monkey closely related to the baboons and to the mandrill. Displaced by logging of their rainforest habitat, drills are among Africa's most endangered mammals.

In the wild, drills are found only in Cross River State in Nigeria, in southwestern Cameroon and on Bioko Island, part of Equatorial Guinea.

Ryder chose the drill because of its close genetic connection to humans, and because in captivity the animals often suffer from diabetes, which researchers are working to treat in humans using stem cell-based therapies.

The northern white rhinoceros, Ceratotherium simum cottoni, was the second candidate. Ryder chose this animal because it is genetically far removed from primates, and because it is one of the most endangered species on the planet. There are only seven animals still in existence, all in captivity. Two of them reside at the San Diego Zoo Safari Park.

The northern white rhino formerly ranged across northwestern Uganda, southern Chad, southern South Sudan, the eastern part of Central African Republic, and northeastern Democratic Republic of the Congo. Poachers reduced their population from 500 to 15 in the 1970s and 1980s. The last surviving wild northern white rhinos were located in the DRC's Garamba National Park. Their planned relocation in 2005 to a wildlife sanctuary in Kenya did not occur because the animals were killed by poachers.

"The best way to manage extinctions is to preserve species and their habitats," said Ryder, "but that's not working all the time."

"Stem cell technology provides some level of hope that they won't have to become extinct even though they've been completely eliminated from their habitats," said Ryder. "I think that if humankind wants to save this species, we're going to have to develop new methodologies."

One of the greatest concerns with small populations such as the northern white rhino is that even if they do reproduce, which has not happened in many years, their genetic diversity is inevitably low, and such inbreeding leads to unhealthy animals.

After a year of trial and error in the lab, the researchers found that the same genes that induce pluripotency in humans also work for the drill and the rhino, and they have the start of a new zoo - the stem cell zoo.

Researchers now are moving toward inducing stem cells to differentiate into sperm or egg cells.

With that accomplished, one possibility is that scientists could take skin cells in the Frozen Zoo from long dead animals, change normal skin cells into stem cells, trigger differentiation into sperm cells, and then combine these with a living animal's eggs through in vitro fertilization.

Genetic diversity would then be reintroduced into the population, making it healthier, larger and more robust.

Or, the scientists say, both eggs and sperm might be produced from the stem cells, with the resulting embryos implanted in live animals, a process that current research suggests could be much more reliable than existing cloning techniques.

Loring said the research team hopes to produce stem cells from other endangered species to expand their stem cell zoo.

For now, they're working to secure funding for this unconventional line of research.

Other scientists are exploring the possibility of producing sperm and eggs from stem cells as a potential solution to human infertility. Loring hopes that some of these researchers might consider initial technique development using stem cells from endangered species.

"I think that work would be a lot easier ethically with endangered species than with humans," she said, "so I suspect some people working in this area would love to have our cells for experiments."

The research appears in an advance online edition of the journal "Nature Methods" dated September 4, 2011.