细胞“返老还童”技术获重大突破

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下面文章从微环境角度研究得到类似结论，但是老龄干细胞的遗传稳定性是困扰其应用的障碍。
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Personal Stem Cell Banks Could Be Staple of Future Health Care

$ v; h6 {% t# ~- x1 W3 y* FScienceDaily (Nov. 1, 2011) — Old stem cells can be rejuvenated by being placed in a young microenvironment, research from The University of Texas Health Science Center San Antonio shows. This raises the possibility that patients' own stem cells may one day be rescued and banked to treat their age-related diseases.
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: k1 {& r, ?; h8 ]& P' fStem cells are immature cells that have the potential to convert into bone, muscle, blood vessels, nerve fibers, and other body cells and tissues. It's no wonder medical science seeks to utilize these versatile cells to restore tissues deteriorated by age, disease or injury.
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Older stem cells are not as robust as young ones, however -- a challenge to clinicians who seek to use patients' own stem cells to treat age-related diseases.
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* z8 ~$ a+ k4 K2 J6 L8 W" h"The number and quality of those cells decline with age, that is very clear," said Xiao-Dong Chen, M.D., Ph.D., a stem cell researcher at the UT Health Science Center. "And, using the patient's own cells can impact results."% u% m8 b$ Z3 _9 k

& [1 T: ]5 {5 E8 \+ x" p8 IDr. Chen's team recently made a discovery in mice that, if translated to humans, could solve this predicament.
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Old cells expand when grown on a young scaffold of tissue
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- B) C5 Q9 O% S# L- \) MDr. Chen suspected that giving stem cells a youthful environment for growth would cause them to regenerate faster. His team extracted mesenchymal stem cells from the bone marrow of 3-month-old mice and 18-month-old mice. The group also obtained extracellular matrix (ECM) from mice of both ages. ECM is a scaffold of connective tissue, such as collagen, which constitutes a majority of the body's structure.% F  i# q5 Q7 `$ q" T9 ]4 l
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The lab team seeded half of the older stem cells on ECM from the 3-month-old mice and half on ECM from the 18-month-old mice. Likewise, half of the young stem cells were seeded on the young ECM and half were seeded on the old ECM.
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Young and old cells showed a 16.1-fold and 17.1-fold expansion, respectively, when grown on ECM from young mice, compared to a 4.1-fold and 3.8-fold expansion when grown on ECM from old mice.
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Finding confirmed in rodent implants
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Next, under the skin of mice, Dr. Chen's group implanted artificial scaffolds seeded with stem cells of both ages that had been grown on young or old ECM. These were left to grow for eight weeks. The researchers targeted bone formation. When the implants were removed, the team found that old cells that had been grown on a young ECM produced just as much bone as young cells, while old cells grown on an old ECM produced no bone. The results were published in the FASEB Journal earlier this year.
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"If this research transfers successfully to clinical application in humans, we could establish personal stem cell banks," Dr. Chen said. "We would collect a small number of older stem cells from patients, put those into our young microenvironment to rescue them -- increasing their number and quality -- then deliver them back into the patient.": j. A! j& ]3 i
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This stem cell rescue and infusion could be done as often as disease treatment requires it, he said. The next step is to repeat the study in human stem cells and ECM.9 [' y( |$ g) h: P  w

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Erasing the Signs of Aging in Human Cells Is Now a Reality! s% B$ K7 E) G" I: a* P
ScienceDaily (Nov. 3, 2011) — Scientists have recently succeeded in rejuvenating cells from elderly donors (aged over 100). These old cells were reprogrammed in vitro to induced pluripotent stem cells (iPSC) and to rejuvenated and human embryonic stem cells (hESC): cells of all types can again be differentiated after this genuine "rejuvenation" therapy. The results represent significant progress for research into iPSC cells and a further step forwards for regenerative medicine.; w! J3 }; y- U! C! G
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, s* m. b& g# vReprogramming elderly senescent cells. (Credit: Image courtesy of INSERM)& `/ a: H" T& ~) Z
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Inserm's AVENIR "Genomic plasticity and aging" team, directed by Jean-Marc Lemaitre, Inserm researcher at the Functional Genomics Institute (Inserm/CNRS/Université de Montpellier 1 and 2) performed the research. The results were published in Genes & Development on November 1, 2011." b4 V9 I3 L) c; Z: v( V3 D

2 e" \' w4 A- q" n5 L2 x1 v# C& AHuman embryonic stem cells (hESC) are undifferentiated multiple-function cells. They can divide and form all types of differentiated adult cells in the body (neurons, cardiac cells, skin cells, liver cells, etc.). Since 2007, a handful of research teams across the world have been capable of reprogramming human adult cells into induced pluripotent cells (iPSC), which have similar characteristics and potential to human embryonic stem cells (hESC). This kind of reprogramming makes it possible to reform all human cell types without the ethical restrictions related to using embryonic stem cells.0 m% X' {  F6 a/ ~* a9 ~
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Until now, research results demonstrated that senescence (the final stage of cellular aging) was an obstacle blocking the use of this technique for therapeutic applications in elderly patients. Today, Inserm researcher Jean-Marc Lemaitre and his team have overcome this obstacle. The researchers have successfully rejuvenated cells from elderly donors, some over 100 years old, thus demonstrating the reversibility of the cellular aging process.7 ?9 e$ a# E  n7 N. a/ G
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To achieve this, they used an adapted strategy that consisted of reprogramming cells using a specific "cocktail" of six genetic factors, while erasing signs of aging. The researchers proved that the iPSC cells thus obtained then had the capacity to reform all types of human cells. They have the physiological characteristics of "young" cells, both from the perspective of their proliferative capacity and their cellular metabolisms.( |+ X) N. |6 ]- ~1 L. g

- y- o- j, h0 s- J$ ?) jA cocktail of six genetic factors.../ ?) o) Y$ @* Q6 k

  i# D2 A/ q* K; u5 j8 n7 kResearchers first multiplied skin cells (fibroblasts) from a 74 year-old donor to obtain the senescence characterized by the end of cellular proliferation. They then completed the in vitro reprogramming of the cells. In this study, Jean-Marc Lemaitre and his team firstly confirmed that this was not possible using the batch of four genetic factors (OCT4, SOX2, C MYC and KLF4) traditionally used. They then added two additional factors (NANOG and LIN28) that made it possible to overcome this barrier.
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Using this new "cocktail" of six factors, the senescent cells, programmed into functional iPSC cells, re-acquired the characteristics of embryonic pluripotent stem cells.9 u( Y4 f( C# f" R; \; o$ I; M8 \
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In particular, they recovered their capacity for self-renewal and their former differentiation potential, and do not preserve any traces of previous aging. To check the "rejuvenated" characteristics of these cells, the researchers tested the reverse process. The rejuvenated iPSC cells were again differentiated to adult cells and compared to the original old cells, as well as to those obtained using human embryonic pluripotetent stem cells (hESC).( ?8 ^3 i, i3 j) t7 ^$ c- [

0 o) c* `' C% D; u6 G: f"Signs of aging were erased and the iPSCs obtained can produce functional cells, of any type, with an increased proliferation capacity and longevity," explains Jean-Marc Lemaitre who directs the Inserm AVENIR team.' B0 J* e) k2 N) U# ~* r

5 ~- [% `. l; U% |…tested on cells taken from donors over the age of 100
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9 p/ g7 n' U. @! x- R- VThe results obtained led the research team to test the cocktail on even older cells taken from donors of 92, 94 and 96, and even up to 101 years old. "Our strategy worked on cells taken from donors in their 100s. The age of cells is definitely not a reprogramming barrier." He concluded. "This research paves the way for the therapeutic use of iPS, insofar as an ideal source of adult cells is provided, which are tolerated by the immune system and can repair organs or tissues in elderly patients." adds the researcher.
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