O'Brien Institute, Victoria, Australia.
J Cardiovasc Pharmacol. 2013 Aug;62(2):122-9. doi: 10.1097/FJC.0b013e31829372fc.
The promise of stem cells to repair the heart after damage or heart attack has not been realized because most such cells are lost after transplantation. A new approach is to grow substantial viable pieces of cardiac tissue from human stem cells by cardiac tissue engineering. Such constructs must be fully vascularized and perfused to ensure the viability of clinically relevant volumes of tissue. This requires careful choice of cells, culture conditions, a biomaterial to act as scaffold, and crucial strategies for vascularization. Autologous stem cells with high plasticity, which would avoid the need for antirejection therapies after transplantation, are an attractive source of both cardiomyocytes and vascular cells. Most stem cells also have inherent paracrine activity, releasing cytoprotective factors and growth-promoting cytokines that can further stimulate tissue regeneration and neovascularization through recruitment of endogenous stem and progenitor cells. Current advances for growing vascularized and functional cardiac constructs with human stem cells are described, bringing us a step closer to the engineering of complex cardiac tissues such as pacemaker, conducting tissue, or contractile myocardial flaps ideal for transplantation. From studies in rats successful transplantation of thin constructs to the ventricle has been reported, but there remain further issues to resolve before larger human constructs will be available to test in the clinic.
干细胞修复损伤或心脏病发作后的心脏的承诺尚未实现,因为大多数此类细胞在移植后丢失。一种新的方法是通过心脏组织工程从人类干细胞中生长出大量有活力的心脏组织片。这些构建体必须充分血管化和灌注,以确保临床相关体积的组织的活力。这需要仔细选择细胞、培养条件、作为支架的生物材料以及血管生成的关键策略。具有高可塑性的自体干细胞是心肌细胞和血管细胞的理想来源,可避免移植后需要抗排斥治疗。大多数干细胞还具有内在的旁分泌活性,释放细胞保护因子和促进生长的细胞因子,通过募集内源性干细胞和祖细胞,进一步刺激组织再生和新血管生成。本文描述了用人干细胞生长血管化和功能心脏构建体的最新进展,使我们更接近于构建复杂的心脏组织,如起搏器、传导组织或用于移植的收缩性心肌瓣。在大鼠研究中,已成功将薄型构建体移植到心室,但在更大的人体构建体可用于临床测试之前,仍需解决其他问题。