2012年12月02日 讯 /生物谷BIOON/ --来自加拿大多伦多大学的研究人员发现一种培养心脏组织的新方法就是通过加入细胞因子将衰老的干细胞转化为像更加年轻的干细胞那样发挥作用的细胞。这项发现可能有朝一日能够让科学家们利用年老病人自己的干细胞培养心脏组织补片(cardiac patch)来修复受损或患病的心脏，同时避免免疫排斥的风险。相关研究结果于2012年11月发表在Journal of the American College of Cardiology期刊上。
多伦多大学化学工程与应用化学系副教授、生物材料与生物医学工程学院(Institute of Biomaterials and Biomedical Engineering, IBBME)功能性心血管组织工程加拿大首席科学家Milica Radisic声称，涉及捐献的骨髓干细胞的干细胞疗法在部分病人群体中有产生免疫排斥的风险。
一种避免免疫排斥风险的方法就是使用病人自己的细胞。但是直到现在，利用年老病人自己的细胞开展的临床试验并不是一种较好的选择，这是因为衰老的细胞往往不像来自年轻病人的细胞那样发挥正常的功能。这正是Radisic和她的同事Ren-Ke Li博士正想要解决的问题。
研究人员首先利用多孔的胶原支架(porous collagen scaffold)构建一种能够培养心脏组织的微环境，并加入年老病人捐献的干细胞。他们然后加入两种促进血管形成的细胞因子---血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(bFGF)---来活化这些干细胞。随后，他们追踪了这些干细胞的变化，结果发现一些衰老因子(特别是p16和RGN)被关闭，从而有效地让它们恢复到更加年轻和健康的状态。
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.
