Chen Chun-Hung, Wei Hao-Ji, Lin Wei-Wen, Chiu Iwen, Hwang Shiaw-Min, Wang Chung-Chi, Lee Wen-Yu, Chang Yen, Sung Hsing-Wen
Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan 30013, Republic of China.
Cardiovasc Res. 2008 Oct 1;80(1):88-95. doi: 10.1093/cvr/cvn149. Epub 2008 Jun 6.
To provide the basis for uniform cardiac tissue regeneration, a spatially uniform distribution of adhered cells within a scaffold is a prerequisite. To achieve this goal, a bioengineered tissue graft consisting of a porous tissue scaffold sandwiched with multilayered sheets of mesenchymal stromal cells was developed.
This tissue graft (sandwiched patch) was used to replace the infarcted wall in a syngeneic Lewis rat model with an experimentally chronic myocardial infarction (MI). There were four treatment groups (n >/= 10): sham, MI, empty patch, and sandwiched patch. After a 7 day culture of the sandwiched patch, a tissue graft with relatively uniform cell concentrations was obtained. The cells were viable and tightly adhered to the tissue scaffold, as the endogenous extracellular matrix inherent with multilayered cell sheets can act as an adhesive agent for cell attachment and retention. At retrieval, the area of the empty patch was relatively enlarged, suggesting reduced structural support, while that of the sandwiched patch remained about the same (P = 0.56). In the immunofluorescent staining, host cells together with neo-microvessels were clearly observed in the empty patch; however, there were still a large number of unfilled pores within the patch. In the sandwiched patch, besides host cells, originally seeded cells were populated within the entire patch. No apparent evidence of apoptotic cell death was found in both studied patches. Thus, the sandwiched-patch-treated hearts demonstrated a better heart function to the empty-patch-treated hearts (P < 0.05).
The results demonstrated that this novel bioengineered tissue graft can serve as a useful cardiac patch to restore the dilated left ventricle and stabilize heart functions after MI.
为实现心脏组织的均匀再生,支架内黏附细胞的空间均匀分布是一个先决条件。为达到这一目标,研发了一种生物工程组织移植物,其由夹有多层间充质基质细胞片的多孔组织支架组成。
该组织移植物(夹心补片)用于在同基因Lewis大鼠实验性慢性心肌梗死(MI)模型中替代梗死壁。有四个治疗组(n≥10):假手术组、MI组、空补片组和夹心补片组。夹心补片培养7天后,获得了细胞浓度相对均匀的组织移植物。细胞存活并紧密黏附于组织支架,因为多层细胞片固有的内源性细胞外基质可作为细胞黏附和保留的黏附剂。取材时,空补片的面积相对增大,提示结构支撑减弱,而夹心补片的面积保持不变(P = 0.56)。免疫荧光染色显示,空补片中可清晰观察到宿主细胞和新生微血管;然而,补片内仍有大量未填充的孔隙。在夹心补片中,除宿主细胞外,最初接种的细胞布满整个补片。在两个研究补片中均未发现明显的凋亡细胞死亡证据。因此,与空补片治疗的心脏相比,夹心补片治疗的心脏表现出更好的心脏功能(P < 0.05)。
结果表明,这种新型生物工程组织移植物可作为一种有用的心脏补片,用于恢复MI后扩张的左心室并稳定心脏功能。