Bone marrow cells adopt the cardiomyogenic fate in vivo
Bone marrow cells adopt the cardiomyogenic fate in vivo
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DOI：
10.1073/pnas.0706406104
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发表时间：
2007-11-06
影响因子：
11.1
通讯作者：
Anversa, Piero
中科院分区：
文献类型：
--
作者：
Rota, Marcello;Kajstura, Jan;Anversa, Piero
成体骨髓细胞（BMC）保留显着程度的发育可塑性，并获得心肌细胞谱系梗死后的可能性已受到挑战，和BMC转分化的概念已受到质疑。争论的中心是缺乏明确的证据支持通过在梗死心脏中注射BMCs来促进心肌再生。由于对基于细胞的心力衰竭治疗的兴趣，几种方法包括基因报告分析、基因标签、细胞基因分型、基于PCR的供体基因检测和量子点直接免疫荧光被用来证明或反驳BMC转分化。我们的研究结果表明，骨髓基质细胞移植，存活，并通过与驻留心肌细胞形成连接复合物在梗死后的备用心肌内生长。BMCs和心肌细胞在其界面表达连接蛋白43和N-cadherin，这种相互作用可能是BMCs采取心肌样命运的关键。随着时间的推移，产生大量的肌细胞和冠状血管。肌细胞显示二倍体DNA含量，最多携带两条性染色体。新旧心肌细胞在钙瞬变中表现出同步性，这为这两个细胞群的功能耦合提供了强有力的证据。因此，BMCs转分化并获得心肌和血管表型，恢复梗死心脏。总之，我们的研究表明，局部递送的BMC产生由整合的心肌细胞和冠状动脉血管组成的新生心肌。这一过程独立于细胞融合发生，并在结构和功能上改善梗死后心脏的结果。
The possibility that adult bone marrow cells (BMCs) retain a remarkable degree of developmental plasticity and acquire the cardiomyocyte lineage after infarction has been challenged, and the notion of BMC transdifferentiation has been questioned. The center of the controversy is the lack of unequivocal evidence in favor of myocardial regeneration by the injection of BMCs in the infarcted heart. Because of the interest in cell-based therapy for heart failure, several approaches including gene reporter assay, genetic tagging, cell geno-typing, PCR-based detection of donor genes, and direct immunofluorescence with quantum dots were used to prove or disprove BMC transdifferentiation. Our results indicate that BMCs engraft, survive, and grow within the spared myocardium after infarction by forming junctional complexes with resident myocytes. BMCs and myocytes express at their interface connexin 43 and N-cadherin, and this interaction may be critical for BMCs to adopt the cardiomyogenic fate. With time, a large number of myocytes and coronary vessels are generated. Myocytes show a diploid DNA content and carry, at most, two sex chromosomes. Old and new myocytes show synchronicity in calcium transients, providing strong evidence in favor of the functional coupling of these two cell populations. Thus, BMCs transdifferentiate and acquire the cardiomyogenic and vascular phenotypes restoring the infarcted heart. Together, our studies reveal that locally delivered BMCs generate de novo myocardium composed of integrated cardiomyocytes and coronary vessels. This process occurs independently of cell fusion and ameliorates structurally and functionally the outcome of the heart after infarction.