Myocardial repair achieved by the intramyocardial implantation of adult cardiomyocytes in combination with bone marrow cells
Myocardial repair achieved by the intramyocardial implantation of adult cardiomyocytes in combination with bone marrow cells
复制标题
DOI：
10.3727/096368908786092702
复制
发表时间：
2008-01-01
影响因子：
3.3
通讯作者：
Hamano, Kimikazu
中科院分区：
文献类型：
--
作者：
Li, Tao-Sheng;Takahashi, Masaya;Hamano, Kimikazu
骨髓细胞产生的多种细胞因子可以保护成体心肌细胞免于凋亡。因此，我们研究了植入成人心肌细胞与骨髓细胞联合进行心肌修复的可行性。从成年大鼠中分离心室心肌细胞并与骨髓细胞共培养。使用阿霉素诱导的心肌病大鼠模型，我们将 6 x 10(5) 成年心肌细胞、3 x 10(7) 骨髓细胞或两者注射到受损心脏中，以进行心肌修复。心肌细胞与骨髓细胞共培养增强了心肌细胞中整合素-β1D和粘着斑激酶的表达，导致培养7天后心肌细胞的存活率增加并细胞凋亡减少。与基线水平相比，单独骨髓细胞植入和心肌细胞与骨髓细胞联合植入的心脏功能得到保留，但单独植入心肌细胞28天后心脏功能显着下降。此外，与单独植入心肌细胞后相比，单独植入骨髓细胞或与心肌细胞组合植入后宿主心肌细胞的凋亡显着减少（p < 0.01）。有趣的是，将成体心肌细胞与骨髓细胞联合植入可显着提高供体心肌细胞的存活率，并诱导供体骨髓干细胞的肌源性分化。我们的研究结果表明，心肌细胞和骨髓细胞可以相互协助和补充；因此，将成体心肌细胞与骨髓细胞联合植入有望成为一种可行的心肌修复新策略。
Various cytokines produced by bone marrow cells can protect adult cardiomyocytes against apoptosis. Thus, we investigated the feasibility of implanting adult cardiomyocytes in combination with bone marrow cells for myocardial repair. Ventricular cardiomyocytes were isolated from adult rats and cocultured with bone marrow cells. Using a rat model of doxorubicin-induced cardiomyopathy, we injected 6 x 10(5) adult cardiomyocytes, 3 x 10(7) bone marrow cells, or both into damaged hearts, for myocardial repair. Coculture of the cardiomyocytes with the bone marrow cells enhanced the expression of integrin-beta 1D and focal adhesion kinase in cardiomyocytes, resulting in increased survival and decreased apoptosis of the cardiomyocytes after 7 days of culture. Compared with the baseline levels, cardiac function was preserved by the implantation of bone marrow cells alone and by the implantation of cardiomyocytes in combination with bone marrow cells, but it was decreased significantly 28 days after the implantation of cardiomyocytes alone. Furthermore, apoptosis of the host cardiomyocytes was decreased significantly after the implantation of bone marrow cells alone, or in combination with cardiomyocytes, compared with that after the implantation of cardiomyocytes alone (p < 0.01). Interestingly, the implantation of adult cardiomyocytes in combination with bone marrow cells resulted in a dramatic increase in the survival of donor cardiomyocytes, and induced the myogenic differentiation of donor bone marrow stem cells. Our findings indicate that cardiomyocytes and bone marrow cells can assist and compliment each other; thus, the implantation of adult cardiomyocytes in combination with bone marrow cells shows promise as a feasible new strategy for myocardial repair.