Division of Cardiothoracic Surgery-Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin 53792-3236, USA.
Cytotherapy. 2011 Apr;13(4):400-6. doi: 10.3109/14653249.2010.529890. Epub 2010 Nov 19.
For many years the human heart has been considered a terminally differentiated organ with no regenerative potential after injury. Recent studies, however, have cast doubt on this long-standing dogma. The objective of this study was to investigate the presence of and characterize mesenchymal stromal cells (MSC) in the adult mouse heart. The impact of MSC on growth and differentiation of adult cardiac stem cells (CSC) was also analyzed.
A combination of lineage-negative/c-kit-negative (Lin(-)/c-kit(-)) immunoselection with a plastic-adhesion technique was used to isolate cardiac-derived MSC. The differentiation capacity and expression of surface markers were analyzed. To investigate the impact of MSC on growth and differentiation of adult CSC, Green Fluorescent Protein (GFP(+)) adult CSC were co-cultured with GFP(-) cardiac-derived MSC.
MSC were present in the adult mouse heart and they met the criteria established to define mouse MSC. They expressed surface markers and were able to differentiate, in a controlled manner, into multiple lineages. In addition, cardiac-derived MSC promoted the survival and expansion of adult CSC in vitro.
MSC can be isolated from the mouse heart and they promote growth and differentiation of adult CSC. The findings from this study could have a significant beneficial impact on future heart failure treatment. Co-culture and co-implantation of cardiac-derived MSC with adult CSC could provide extensive cardiac regeneration and maintenance of the CSC population after implanted into the heart.
多年来,人类心脏一直被认为是终末分化器官,在受伤后没有再生潜力。然而,最近的研究对这一长期以来的教条提出了质疑。本研究的目的是研究成年小鼠心脏中是否存在间质基质细胞(MSC),并对其特征进行分析。同时分析 MSC 对成年心脏干细胞(CSC)的生长和分化的影响。
采用谱系阴性/ c-kit 阴性(Lin(-)/c-kit(-))免疫阴性选择和塑料粘附技术相结合的方法分离心脏来源的 MSC。分析其分化能力和表面标志物的表达。为了研究 MSC 对成年 CSC 生长和分化的影响,将 GFP(+)成年 CSC 与 GFP(-)心脏来源的 MSC 共培养。
MSC 存在于成年小鼠心脏中,并且符合定义小鼠 MSC 的标准。它们表达表面标志物,并能以可控的方式分化为多个谱系。此外,心脏来源的 MSC 可促进成年 CSC 在体外的存活和扩增。
可以从小鼠心脏中分离出 MSC,并且可以促进成年 CSC 的生长和分化。这项研究的结果可能对未来的心力衰竭治疗产生重大的有益影响。将心脏来源的 MSC 与成年 CSC 共培养和共植入,可以在植入心脏后提供广泛的心脏再生和 CSC 群体的维持。