生物谷報(bào)道：斯洛伐克科學(xué)院癌癥研究所的研究人員最近成功從人類脂肪組織中提取出間充質(zhì)干細(xì)胞（mesenchymal stem cells），并通過基因工程方法使其合成,、分泌導(dǎo)向并破壞腫瘤的“自殺基因”,。這種基因療法能夠進(jìn)攻逃避現(xiàn)有檢測技術(shù)、治療方法的小腫瘤遷移物,。詳細(xì)內(nèi)容刊登于7月1日Cancer Research雜志,。
課題負(fù)責(zé)人Cestmir Altaner博士說，這些脂肪來源的干細(xì)胞有望用于以細(xì)胞為基礎(chǔ)的個性化治療,。每個人都多多少少有些多余的脂肪,，脂肪組織也許會成為治療癌癥所需的細(xì)胞源。
間充質(zhì)干細(xì)胞通過更新細(xì)胞,，修復(fù)受損的組織和器官,。研究人員發(fā)現(xiàn)在混有癌細(xì)胞準(zhǔn)備向?qū)嶓w腫瘤發(fā)展的正常細(xì)胞群中也有間充質(zhì)干細(xì)胞，推測這些間充質(zhì)干細(xì)胞會將腫瘤當(dāng)作受損器官并向腫瘤遷移,，因此可被用來尋找原發(fā)腫瘤和小的轉(zhuǎn)移瘤。這些干細(xì)胞還有一定的可塑性,，即能夠根據(jù)給定組織的微環(huán)境發(fā)生特化,。
從人類脂肪組織提取出間充質(zhì)干細(xì)胞后，研究人員開始尋找一種比治療結(jié)腸癌標(biāo)準(zhǔn)化療劑5-fluorouracil (5-FU)對正常細(xì)胞毒副作用更小的途徑,。他們將得到的間充質(zhì)干細(xì)胞在培養(yǎng)基中大量擴(kuò)增,，然后用反轉(zhuǎn)錄病毒載體將胞嘧啶脫氨基酶(cytosine deaminase，CD)基因插入細(xì)胞的基因組中,，這種基因?qū)⒏杉?xì)胞中一種毒副作用較小的藥物5-fluorocytosine (5-FC)轉(zhuǎn)化為5-FU,。接著,，研究人員用化療法殺滅腫瘤，產(chǎn)生一個致死性的旁觀者效應(yīng)（by-stander effect,，是指殺腫瘤細(xì)胞的導(dǎo)彈，在靶向腫瘤細(xì)胞集中營給以殺傷外,，也可殺傷一部腫瘤鄰近地帶的腫瘤細(xì)胞）,。
在移植有人類結(jié)腸癌的裸鼠（沒有免疫功能）中，研究人員首先注射遺傳工程得到的間充質(zhì)干細(xì)胞,，然后注射5-FC,。結(jié)果顯示，腫瘤生長抑制率達(dá)到68.5％,，沒有一只小鼠出現(xiàn)毒副作用,。研究人員說，雖然沒有一只小鼠被完全治愈,，但我們的程序卻非常有效,，甚至只用了一次干細(xì)胞。很明顯,，重復(fù)治療效果會更好,。
普通的間充質(zhì)干細(xì)胞有多種來源（比如骨髓）但產(chǎn)量原沒有脂肪組織中得到的多。最簡單的方法是從切除腫瘤的外科手術(shù)中獲得脂肪組織,，吸脂法也可以用于分離間充質(zhì)干細(xì)胞,，這兩個過程都比從患者中收集骨髓容易的多。
英文原文：
http://www.aacr.org/home/about-us/news.aspx?d=786
Fat Kills Cancer: Turning Stem Cells Taken from Fat Tissue into Personalized, Cancer-Targeted Therapeutics
July 3, 2007
PHILADELPHIA - Researchers in Slovakia have been able to derive mesenchymal stem cells from human adipose, or fat, tissue and engineer them into "suicide genes" that seek out and destroy tumors like tiny homing missiles. This gene therapy approach is a novel way to attack small tumor metastases that evade current detection techniques and treatments, the researchers conclude in the July 1 issue of Cancer Research, a journal of the American Association for Cancer Research.
"These fat-derived stem cells could be exploited for personalized cell-based therapeutics," said the study's lead investigator, Cestmir Altaner, Ph.D., D.Sc., an associate professor in the Cancer Research Institute of the Slovak Academy of Sciences in Bratislava. "Nearly everyone has some fat tissue they can spare, and this tissue could be a source of cells for cancer treatment that can be adapted into specific vehicles for drug transport."
Mesenchymal stem cells help repair damaged tissue and organs by renewing injured cells. They are also found in the mass of normal cells that mix with cancer cells to make up a solid tumor. Researchers believe mesenchymal stem cells "see" a tumor as a damaged organ and migrate to it, and so might be utilized as a "vehicle" for treatment that can find both primary tumors and small metastases. These stem cells also have some plasticity, which means they can be converted by the micro environment of a given tissue into specialized cells, Altaner says.
After extracting the stem cells from human fat tissue the researchers worked to find a less toxic way to treat colon cancer than the standard-of-care chemotherapy agent, 5-fluorouracil (5-FU), which can produce toxic side effects in normal cells. They expanded the number of mesenchymal stem cells in the laboratory and then used a retrovirus vector to insert the gene cytosine deaminase into the cell. This gene can convert a less toxic drug, 5-fluorocytosine (5-FC), to 5-FU inside the stem cells, and the chemotherapy can then seep out into the tumor, producing a lethal by-stander effect.
In nude mice - animals with an inhibited immune system - engrafted with human colon cancer, the researchers first injected the engineered mesenchymal stem cells, then 5-FC. They found tumor growth was inhibited by up to 68.5 percent in the animals, and none of the mice exhibited any signs of toxic side effects.
However, none of the animals remained tumor-free. "The procedure was quite effective even though we applied the stem cells just once. Obviously, repeated treatment will increase the efficacy, as would using this strategy in combination with other treatments," Altaner said.
Normal mesenchymal cells can be isolated from various sources, including bone marrow, but the yield is not nearly as great as what the researchers derived from fat tissue. Removal of fat tissue during surgery to remove a tumor would be simple, says Altaner. Liposuction could also be used to isolate mesenchymal stem cells can also be gathered and isolated through liposuction, and the cells frozen in liquid nitrogen for future therapeutic use. Both processes would be easier than taking bone marrow from a patient, Altaner said.
The study was funded by grants from the Slovak Academy of Sciences and the League Against Cancer, and support from the Slovakian national cancer genomics program.
The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.
