Name: reprogramming mature cells into stem cells
Uploaded: 2019-03-11T09:21:22.000Z
Duration: 1 min 13 s
Channel: JoVE

人工多能性幹細胞(iPSC)は、実験室で未分化胚性幹細胞に 近づけて設計された，皮膚細胞などの成熟した分化細胞です。すなわち，分裂，多能性で，体内であらゆる細胞型を産生することができます。例えば、網膜細胞は損傷した網膜組織を 置換するために使用できます。iPSCを作成するには、皮膚線維芽細胞のような成熟細胞を 患者から採取して培養します。次に，ふつうは，転写因子の遺伝子は ウイルスベクターによって細胞核に送達され、そこで遺伝子はゲノムに組み込まれます。転写因子は、胚性幹細胞によって 発現される遺伝子を 効果的に脱分化させ、それらを多能性状態にします。細胞は分裂できるようになり，培養中の特定の細胞型を産生するようにできるのが理想的である。その後、怪我または病気を治療するために、新しい細胞を患者に移植します。患者自身の細胞に由来するので、拒絶反応の危険性は最小限です。

濱崎 隆、Nihal El Rouby、Natalie C. Fredette、Katherine E. Santostefano、寺田 尚弘. "Concise Review: Induced Pluripotent Stem Cell Research in the Era of Precision Medicine." Stem Cells (Dayton, Ohio) 35, no. 3 (March 2017): 545–50.[<a href="https://doi.org/10.1002/stem.2570" target="__blank">ソース</a>]。

誘導多能性幹細胞（ips細胞）

Induced Pluripotent Stem Cells

幹細胞とは、分裂してさまざまな種類の細胞を作り出す未分化な細胞です。通常、特定の種類の細胞に分化した細胞は、もはや分裂しない「ポスト有糸分裂」状態にあります。しかし、科学者たちは、これらの成熟した細胞を再プログラムする方法を発見しました。この方法では、細胞を脱分化させ、特殊化していない増殖可能な状態に戻すことができます。これらの細胞は、胚性幹細胞のように多能性を持ち、あらゆる種類の細胞を作り出すことができるため、人工多能性幹細胞（iPSC）と呼ばれています。
 
 iPSCは医療分野での利用価値があります。例えば、黄斑変性症で網膜が損傷した患者が、自分の体内の別の細胞から必要な細胞を移植できます。これは自家移植と呼ばれ、個人間で組織を移植する際に発生する移植拒絶反応のリスクを軽減できます。 
 
 <h4>プロセス</h4>
 
 iPSCを作るには、人の皮膚の線維芽細胞や血液細胞などの成熟した細胞を培養します。次に、ウイルスベクターを使って複数の転写因子の遺伝子を細胞内に導入し、細胞内の機械を使って転写因子タンパク質を発現させます。そして、転写因子は、胚性幹細胞が発現する他の多くの遺伝子をオンにし、細胞を未分化、増殖性、多能性の状態に戻します。 
 
 iPSCが本当に胚性幹細胞と同等のものかどうかはまだ研究中ですが、類似しているようで、体の3つの生殖細胞層すべてから細胞を作り出すことができます。他の幹細胞と同様に、科学者たちはiPSCから特定の種類の細胞の分化を効率的に促進し、必要な種類の細胞を十分に生産できるようにする方法を学んでいます。
 
 <h4>初期の臨床試験</h4>
 
 最初の臨床試験では、加齢黄斑変性症の患者にiPSCから得られた網膜細胞を移植しました。その後、パーキンソン病、心臓病、脊髄損傷の治療を目的としたいくつかのiPSC臨床試験が承認されました。また、患者から採取した細胞をiPSCにして、実験室で患者の病気を研究することも行われています。一般的に、iPSCは科学研究のためのもう一つの幹細胞の供給源となっています。

誘導多能性幹細胞（iPS細胞）

幹細胞は、さまざまな種類の細胞を分裂させて生成する未分化細胞です。通常、特定の細胞に分化した細胞は......

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reprogramming mature cells into stem cells

Reprogramming mature cells into stem cells lets scientists turn specialized cells back into an unspecialized state. These cells are called induced pluripotent stem cells, or iPSCs. Like embryonic stem cells, iPSCs are pluripotent, which means they can form all cell types.

To make iPSCs, researchers start with mature cells such as skin fibroblasts or blood cells. The cells are grown in culture, and genes for several transcription factors are delivered with a viral vector. The cells then make those transcription factor proteins, which switch on other genes that are active in embryonic stem cells and return the cells to a proliferative, undifferentiated, and pluripotent state.

iPSCs may be useful in medicine because they can come from a patient’s own body. For example, cells needed to repair a damaged retina in age-related macular degeneration could be made from that same patient’s cells. This autologous transplantation lowers the risk of transplant rejection that can happen when tissue is moved between different people.

Scientists are still studying whether iPSCs are truly equivalent to embryonic stem cells, but they appear to be similar and can produce cells from all three germ layers. Researchers are also working on ways to direct iPSCs to become specific cell types in efficient amounts. Early clinical trials have used iPSC-derived retinal cells for macular degeneration, and other trials have been approved for Parkinson’s disease, heart disease, and spinal cord injury. Patient cells turned into iPSCs are also helping scientists study disease in the lab.

Reprogramming Mature Cells into Stem Cells

reprogramming-mature-cells-into-stem-cells

what is genetic engineering?

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Genetic engineering changes an organism’s DNA to add useful traits. Scientists use it in bacteria, plants, animals, and even viruses for research, medicine, agriculture, and industry. It can bring major benefits, but it also raises ethical concerns about humans and the food supply. This work is possible because DNA has the same basic structure and genetic code across life. That shared code lets scientists modify DNA in several ways. One method is CRISPR/Cas9, often called molecular scissors,...

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recombinant dna technology

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Complementary DNA, or cDNA, is made from messenger RNA (mRNA) so scientists can study which genes are active in cells and tissues. Only genes that are transcribed into mRNA are expressed. By extracting mRNA from cells, researchers can compare gene expression across samples. cDNA is produced by reverse transcription. This process copies mRNA into DNA, which is useful because mRNA does not contain introns, or non-coding regions, and other regulatory sequences. As a result, cDNA can help...

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Knockout mice help researchers study gene function by showing what happens when a gene is turned off. These engineered animals are also useful for modeling human diseases such as cancer, Parkinson’s disease, and diabetes. A specific gene can be targeted by using a targeting vector, which is a piece of engineered DNA that replaces the normal gene and inactivates it. The vector has matching DNA sequences on both ends. These homologous sequences let the vector swap in for the target gene through...

crispr

CRISPR-Cas9 Gene Editing in Action

CRISPR-Cas9 is a genome editing tool that lets scientists change DNA at a specific location. It can add, remove, or rearrange genetic material. Researchers study it because it may help treat genetic disorders such as hemophilia and sickle cell anemia. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, and Cas9 is a CRISPR-associated protein 9. The basic system includes a Cas9 endonuclease, which is an enzyme that cuts DNA, and a small RNA that guides Cas9 to the...

gene therapy

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Gene therapy is a technique used to treat serious disease by adding a gene to a person’s cells. The added gene may be a healthy copy of a mutated gene. It may also be a different gene that inactivates or compensates for the disease-causing gene. One example is severe combined immunodeficiency, or SCID, caused by a mutation in the gene for adenosine deaminase. In that case, a working copy of the gene can be inserted so the patient’s cells make the enzyme again. This can cure the disease in some...

embryonic stem cells

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adult stem cells

Adult Stem Cells in the Small Intestine

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induced pluripotent stem cells

Reprogramming mature cells into stem cells lets scientists turn specialized cells back into an unspecialized state. These cells are called induced pluripotent stem cells, or iPSCs. Like embryonic stem cells, iPSCs are pluripotent, which means they can form all cell types. To make iPSCs, researchers start with mature cells such as skin fibroblasts or blood cells. The cells are grown in culture, and genes for several transcription factors are delivered with a viral vector. The cells then make...

reproductive cloning

Cloning Animals with SCNT

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genomics

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Genomics studies the full set of genetic material in an organism. In humans, that genome includes the DNA carried in 23 pairs of chromosomes in the nucleus, along with mitochondrial DNA. Genomics looks at both coding DNA and non-coding DNA, which helps scientists study how living things are built and how they differ. This field is useful in many areas of biology and medicine. Scientists use genomics to build phylogenetic trees, improve crop productivity and sustainability, help with criminal...

key terms and concepts

Learn how mature cells are reprogrammed into induced pluripotent stem cells, why iPSCs matter for transplants, and how they are used in research and clinical trials.

Reprogramming Mature Cells into Stem Cells | JoVE K12

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Reprogramming Mature Cells into Stem Cells

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