2012年10月9日 訊 /生物谷BIOON/ --來(lái)自美國(guó)希達(dá)-西奈醫(yī)學(xué)院馬克辛-多尼茲神經(jīng)外科研究所(Cedars-Sinai's Maxine Dunitz Neurosurgical Institute)的研究人員發(fā)現(xiàn)一種血管形成基因促進(jìn)人骨髓干細(xì)胞能夠持續(xù)修復(fù)胰島素依賴(lài)性糖尿病小鼠模式動(dòng)物的受損胰腺,。相關(guān)研究發(fā)表在PLoS ONE期刊上,。
這些發(fā)現(xiàn)為人們理解胰島素產(chǎn)生細(xì)胞(insulin-producing cell)的再生機(jī)制提供新的深入認(rèn)識(shí)和，同時(shí)提供新的證據(jù)表明有朝一日可能利用糖尿病患者自己的骨髓來(lái)治療疾病,。
十年前,，科學(xué)家們就開(kāi)始研究利用骨髓干細(xì)胞來(lái)再生胰腺,。最近的研究涉及利用幾個(gè)胰腺小鼠相關(guān)的基因和被稱(chēng)作“移植到胰腺或注射到血液中”的遞送方法，這些研究在一些實(shí)驗(yàn)室小鼠體內(nèi)已證實(shí)骨髓干細(xì)胞療法能夠逆轉(zhuǎn)或改善糖尿病病情,。但是很少有人知道干細(xì)胞如何影響胰島β細(xì)胞---即產(chǎn)生胰島素的胰腺細(xì)胞---或者科學(xué)家們?nèi)绾文軌虼龠M(jìn)β細(xì)胞持續(xù)更新和胰島素持續(xù)產(chǎn)生,。
當(dāng)來(lái)自希達(dá)-西奈醫(yī)學(xué)院馬克辛·多尼茲神經(jīng)外科研究所的研究人員對(duì)骨髓干細(xì)胞進(jìn)行基因修飾讓它們表達(dá)一種編碼血管內(nèi)皮生長(zhǎng)因子(vascular endothelial growth factor, VEGF)的基因時(shí)，小鼠胰腺能夠再生新的β細(xì)胞,，因而能夠持續(xù)修復(fù)胰腺,。這種經(jīng)過(guò)VEGF基因修飾的干細(xì)胞促進(jìn)所需的血管生長(zhǎng)和輔助激活涉及胰島素產(chǎn)生的基因。然而,，經(jīng)過(guò)另一個(gè)不同基因PDX1修飾的骨髓干細(xì)胞只能暫時(shí)產(chǎn)生β細(xì)胞,，但不能持續(xù)地產(chǎn)生β細(xì)胞?；騊DX1在β細(xì)胞的發(fā)育和維持中發(fā)生著重要的作用,。
論文通信作者John S. Yu博士說(shuō)，“我們的研究是第一次證實(shí)在胰腺損傷之后,，VEGF導(dǎo)致血管再生和復(fù)原,。它證明利用經(jīng)過(guò)基因修飾表達(dá)基因VEGF的骨髓干細(xì)胞在治療胰島素依賴(lài)性糖尿病中可能具有臨床益處。”
在當(dāng)前這項(xiàng)為期6周的研究中,，研究人員發(fā)現(xiàn)在9只接受經(jīng)過(guò)基因VEGF修飾的骨髓干細(xì)胞注射的小鼠中,，有5只小鼠的糖尿病病情得到逆轉(zhuǎn)，而且在剩下的研究時(shí)間中,，這5只小鼠的血糖將近恢復(fù)到正常的水平,。其他的4只小鼠存活下來(lái)，并且體重增加,，這就表明即便不能完全促進(jìn)病情逆轉(zhuǎn),，這種治療也是有益的。實(shí)驗(yàn)室研究隨后證實(shí)這種經(jīng)過(guò)基因修飾的骨髓干細(xì)胞在胰腺中存活和生長(zhǎng),，并且支持血管和β細(xì)胞再生,。
不過(guò)，研究人員提醒道,，盡管這項(xiàng)研究和其他相關(guān)的研究有助于科學(xué)家們更好地理解涉及胰腺再生的過(guò)程和途徑,，但是在人類(lèi)臨床試驗(yàn)?zāi)軌蜷_(kāi)始之前，還需開(kāi)展更多的研究。(生物谷Bioon.com)
doi: 10.1371/journal.pone.0042177
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β-Cell Regeneration Mediated by Human Bone Marrow Mesenchymal Stem Cells
Anna Milanesi1,2, Jang-Won Lee3, Zhenhua Li3, Stefano Da Sacco4, Valentina Villani4, Vanessa Cervantes3, Laura Perin4, John S. Yu
Bone marrow mesenchymal stem cells (BMSCs) have been shown to ameliorate diabetes in animal models. The mechanism, however, remains largely unknown. An unanswered question is whether BMSCs are able to differentiate into β-cells in vivo, or whether BMSCs are able to mediate recovery and/or regeneration of endogenous β-cells. Here we examined these questions by testing the ability of hBMSCs genetically modified to transiently express vascular endothelial growth factor (VEGF) or pancreatic-duodenal homeobox 1 (PDX1) to reverse diabetes and whether these cells were differentiated into β-cells or mediated recovery through alternative mechanisms. Human BMSCs expressing VEGF and PDX1 reversed hyperglycemia in more than half of the diabetic mice and induced overall improved survival and weight maintenance in all mice. Recovery was sustained only in the mice treated with hBMSCs-VEGF. However, de novo β-cell differentiation from human cells was observed in mice in both cases, treated with either hBMSCs-VEGF or hBMSCs- PDX1, confirmed by detectable level of serum human insulin. Sustained reversion of diabetes mediated by hBMSCs-VEGF was secondary to endogenous β-cell regeneration and correlated with activation of the insulin/IGF receptor signaling pathway involved in maintaining β-cell mass and function. Our study demonstrated the possible benefit of hBMSCs for the treatment of insulin-dependent diabetes and gives new insight into the mechanism of β-cell recovery after injury mediated by hBMSC therapy.
