2012年12月02日 訊 /生物谷BIOON/ --來自加拿大多倫多大學(xué)的研究人員發(fā)現(xiàn)一種培養(yǎng)心臟組織的新方法就是通過加入細(xì)胞因子將衰老的干細(xì)胞轉(zhuǎn)化為像更加年輕的干細(xì)胞那樣發(fā)揮作用的細(xì)胞,。這項(xiàng)發(fā)現(xiàn)可能有朝一日能夠讓科學(xué)家們利用年老病人自己的干細(xì)胞培養(yǎng)心臟組織補(bǔ)片(cardiac patch)來修復(fù)受損或患病的心臟,，同時(shí)避免免疫排斥的風(fēng)險(xiǎn)。相關(guān)研究結(jié)果于2012年11月發(fā)表在Journal of the American College of Cardiology期刊上,。
多倫多大學(xué)化學(xué)工程與應(yīng)用化學(xué)系副教授,、生物材料與生物醫(yī)學(xué)工程學(xué)院(Institute of Biomaterials and Biomedical Engineering, IBBME)功能性心血管組織工程加拿大首席科學(xué)家Milica Radisic聲稱,，涉及捐獻(xiàn)的骨髓干細(xì)胞的干細(xì)胞療法在部分病人群體中有產(chǎn)生免疫排斥的風(fēng)險(xiǎn)。
一種避免免疫排斥風(fēng)險(xiǎn)的方法就是使用病人自己的細(xì)胞,。但是直到現(xiàn)在,，利用年老病人自己的細(xì)胞開展的臨床試驗(yàn)并不是一種較好的選擇，這是因?yàn)樗ダ系募?xì)胞往往不像來自年輕病人的細(xì)胞那樣發(fā)揮正常的功能,。這正是Radisic和她的同事Ren-Ke Li博士正想要解決的問題,。
研究人員首先利用多孔的膠原支架(porous collagen scaffold)構(gòu)建一種能夠培養(yǎng)心臟組織的微環(huán)境，并加入年老病人捐獻(xiàn)的干細(xì)胞,。他們?nèi)缓蠹尤雰煞N促進(jìn)血管形成的細(xì)胞因子---血管內(nèi)皮生長(zhǎng)因子(VEGF)和堿性成纖維細(xì)胞生長(zhǎng)因子(bFGF)---來活化這些干細(xì)胞,。隨后,，他們追蹤了這些干細(xì)胞的變化，結(jié)果發(fā)現(xiàn)一些衰老因子(特別是p16和RGN)被關(guān)閉,，從而有效地讓它們恢復(fù)到更加年輕和健康的狀態(tài),。
doi: 10.1016/j.jacc.2012.08.985
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Aged Human Cells Rejuvenated by Cytokine Enhancement of Biomaterials for Surgical Ventricular Restoration
Kai Kang, MD; Lu Sun, MD; Yun Xiao, BSc; Shu-Hong Li, MD, MSc; Jun Wu, MD, MSc; Jian Guo, MD, PhD; Shu-Ling Jiang, MD; Lei Yang, MD; Terrence M. Yau, MD, MSc; Richard D. Weisel, MD; Milica Radisic, PhD, PEng; Ren-Ke Li, MD, PhD
Objectives This study investigated whether cytokine enhancement of a biodegradable patch could restore cardiac function after surgical ventricular restoration (SVR) even when seeded with cells from old donors.
Background SVR can partially restore heart size and improve function late after an extensive anterior myocardial infarction. However, 2 limitations include the stiff synthetic patch used and the limited healing of the infarct scar in aged patients.
Methods We covalently immobilized 2 proangiogenic cytokines (vascular endothelial growth factor and basic fibroblast growth factor) onto porous collagen scaffolds. We seeded human mesenchymal stromal cells from young (50.0 ± 8.0 years, N = 4) or old (74.5 ± 7.4 years, N = 4) donors into the scaffolds, with or without growth factors. The patches were characterized and used for SVR in a rat model of myocardial infarction. Cardiac function was assessed.
Results In vitro results showed that cells from old donors grew slower in the scaffolds. However, the presence of cytokines modulated the aging-related p16 gene and enhanced cell proliferation, converting the old cell phenotype to a young phenotype. In vivo studies showed that 28 days after SVR, patches seeded with cells from old donors did not induce functional recovery as well as patches seeded with young cells. However, cytokine-enhanced patches seeded with old cells exhibited preserved patch area, prolonged cell survival, and augmented angiogenesis, and rats implanted with these patches had better cardiac function. The patch became an elastic tissue, and the old cells were rejuvenated.
Conclusions This sustained-release, cytokine-conjugated system provides a promising platform for engineering myocardial tissue for aged patients with heart failure.
