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InStorySTEM_TissueRepair 美國聖地牙哥的諾華研究基金會基因體中心,發現一種稱作Kartogenin分子,可以促進間葉幹細胞分化成軟骨細胞。經由小鼠的動物實驗證實,注射Kartogenin可以改善因關節炎引起的軟骨損傷,重獲關節功能且無疼痛感。這項治療退化性關節炎--骨關節炎(osteoarthritis;OA)的新發現,刊登於4月份科學期刊<Science>。
 
軟骨含有間葉幹細胞,能分化成軟骨細胞(chondrocytes)形成結締組織。因受傷或長期使用關節而罹患骨關節炎(最常見的關節炎)的病患,其軟骨受到嚴重破壞,Kartogenin能促進間葉幹細胞的分化,為軟骨修復的重要步驟。
 
參與這項研究的主要作者- 諾華研究基金會基因體中心的分子生物學家Kristen Johnson,與研究團隊共同篩選軟骨中22000個分子,發現誘導間葉幹細胞分化成軟骨細胞的Kartogenin。在患有類似骨關節炎的小鼠實驗證實,該分子可以啟動蛋白聚醣(aggrecan)和膠原蛋白II(collagen II)基因表現,降低發炎物質-軟骨低聚基質蛋白(cartilage oligomeric matrix protein)含量,使小鼠受損膝關節能在42天內重獲承重能力。另外,kartogenin可以抑制間葉幹細胞中的細絲蛋白A(filamin A),促使間葉幹細胞分化成軟骨細胞,保護並修復受損軟骨。 
 
 
許多人到老年時期會發生骨關節炎,然而透過外科手術清除受損軟骨的成功率有限,此外,以手術促進骨末端纖維狀軟骨增生,又因失去自然軟骨帽而成功率不高。軟骨再生已經成為整形外科醫學的主要目標,而這項研究帶來重大的意義。
 
 
Stem cell treatment spurs cartilage growth

A small molecule dubbed kartogenin encourages stem cells to take on the characteristics of cells that make cartilage, a new study shows. And treatment with kartogenin allowed many mice with arthritis-like cartilage damage in a knee to regain the ability to use the joint without pain.

The findings provide new clues in the long-running effort to find ways to regenerate cartilage, a central puzzle in the battle against osteoarthritis, scientists report online April 5 in Science.

The new approach taps into mesenchymal stem cells, which naturally reside in cartilage and give rise to cells that make connective tissue. These include chondrocytes, the only cells in the body that manufacture cartilage. Kartogenin steers the stem cells to wake up and take on cartilage-making duties. This is an essential step in the cartilage repair that falls behind in people with osteoarthritis, the most common kind of arthritis, which develops from injury or long-term joint use.

Johnson and her colleagues screened 22,000 compounds in cartilage and found that one, kartogenin, induced stem cells to take on the characteristics of chondrocytes. The molecule turned on genes that make cartilage components called aggrecan and collagen II. Tests of mice with cartilage damage similar to osteoarthritis showed that kartogenin injections lowered levels of a protein called cartilage oligomeric matrix protein. People with osteoarthritis have an excess of the protein, which is considered a marker of disease severity. Kartogenin also enabled mice with knee injuries to regain weight-bearing capacity on the joint within 42 days.

Lab work revealed that kartogenin inhibits a protein called filamin A in the mesenchymal stem cells. This unleashes other compounds that can then orchestrate the activity of genes useful in turning the stem cells into functional chondrocytes. In so doing, Johnson says, kartogenin seems to protect and repair cartilage.

Millions of people develop osteoarthritis as they reach old age. Cartilage serves as the shock absorber of the skeleton, but surgery to clean out torn cartilage has limited success, as does surgery to induce growth of a fibrous kind of coating at the ends of bones that have lost their natural cartilage caps. This losing battle leaves bone-on-bone friction, inflammation and pain.

Source from http://www.sciencenews.org/view/generic/id/339669/title/Stem_cell_treatment_spurs_cartilage_growth

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