Hendrikx Marc, Fanton Yanick, Willems Leen, Daniels Annick, Declercq Jeroen, Windmolders Severina, Hensen Karen, Koninckx Remco, Jamaer Luc, Dubois Jasperina, Dilling-Boer Dagmara, Vandekerkhof Jos, Hendrikx Filip, Bijnens Eric, Heuts Nick, Robic Boris, Bito Virginie, Ameloot Marcel, Steels Paul, Rummens Jean-Luc
Jessa Ziekenhuis vwz Department of Cardiothoracic and Vascular Surgery, Hasselt, Belgium.
Curr Med Chem. 2016;23(23):2421-38. doi: 10.2174/0929867323666160525114735.
Traditionally the heart is considered a terminally differentiated organ. However, at the beginning of this century increased mitotic activity was reported in ischemic and idiopathic dilated cardiomyopathy hearts, compared to healthy controls, underscoring the potential of regeneration after injury. Due to the presence of adult stem cells in bone marrow and their purported ability to differentiate into other cell lineages, this cell population was soon estimated to be the most suited candidate for cardiac regeneration. Clinical trials with autologous bone marrow-derived mononuclear cells, using either an intracoronary or direct intramyocardial injection approach consistently showed only minor improvement in global left ventricular ejection fraction. This was explained by their limited cardiomyogenic differentiation potential. To obtain more convincing improvement in cardiac function, based on true myocardial regeneration, the focus of research has shifted towards resident cardiac progenitor cells. Several isolation procedures have been described: the c-kit surface marker was the first to be used, however experimental research has clearly shown that c-kit+ cells only marginally contribute to regeneration post myocardial infarction. Sphere formation was used to isolate the so-called cardiosphere derived cells (CDC), and also in this cell population cardiomyogenic differentiation is a rare event. Recently a new type of stem cells derived from atrial tissue (cardiac atrial stem cells - CASCs) was identified, based on the presence of the enzyme aldehyde dehydrogenase (ALDH). Those cells significantly improve both regional and global LV ejection fraction, based on substantial engraftment and consistent differentiation into mature cardiomyocytes (98%).
传统上，心脏被认为是终末分化器官。然而，在本世纪初，有报道称，与健康对照相比，缺血性和特发性扩张型心肌病心脏中的有丝分裂活性增加，这突出了损伤后心脏再生的潜力。由于骨髓中存在成体干细胞及其据称能分化为其他细胞谱系的能力，这一细胞群体很快被认为是心脏再生最适合的候选者。使用冠状动脉内或直接心肌内注射方法进行的自体骨髓来源单核细胞的临床试验始终显示，整体左心室射血分数仅有轻微改善。这是由于它们有限的心肌生成分化潜能所致。为了基于真正的心肌再生在心脏功能方面获得更令人信服的改善，研究重点已转向心脏驻留祖细胞。已经描述了几种分离方法：c-kit表面标志物是最早使用的，然而实验研究清楚地表明，c-kit+细胞对心肌梗死后的再生贡献很小。球体形成被用于分离所谓的球源细胞（CDC），并且在这个细胞群体中，心肌生成分化也是罕见事件。最近，基于醛脱氢酶（ALDH）的存在，一种源自心房组织的新型干细胞（心脏心房干细胞 - CASCs）被鉴定出来。基于大量植入和持续分化为成熟心肌细胞（98%），这些细胞显著改善了局部和整体左心室射血分数。
