Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
J Cardiovasc Transl Res. 2009 Jun;2(2):173-81. doi: 10.1007/s12265-009-9090-0. Epub 2009 Mar 19.
Bone-marrow-derived stem cells have displayed the potential for myocardial regeneration in animal models as well as in clinical trials. Unfractionated bone marrow mononuclear cell (MNC) population is a heterogeneous group of cells known to include a number of stem cell populations. Cells in the side population (SP) fraction have a high capacity for differentiation into multiple lineages. In the current study, we investigated the role of murine and human bone-marrow-derived side population cells in myocardial regeneration. In these studies, we show that mouse bone-marrow-derived SP cells expressed the contractile protein, alpha-actinin, following culture with neonatal cardiomyocytes and after delivery into the myocardium following injury. Moreover, the number of green-fluorescent-protein-positive cells, of bone marrow side population origin, increased progressively within the injured myocardium over 90 days. Transcriptome analysis of these bone marrow cells reveals a pattern of expression consistent with immature cardiomyocytes. Additionally, the differentiation capacity of human granulocyte colony-stimulating factor stimulated peripheral blood stem cells were assessed following injection into injured rat myocardium. Bone marrow mononuclear cell and side population cells were both readily identified within the rat myocardium 1 month following injection. These human cells expressed human-specific cardiac troponin I as determined by immunohistochemistry as well as numerous cardiac transcripts as determined by polymerase chain reaction. Both human bone marrow mononuclear cells and human side population cells augmented cardiac systolic function following a modest drop in function as a result of cryoinjury. The augmentation of cardiac function following injection of side population cells occurred earlier than with bone marrow mononuclear cells despite the fact that the number of side population cells used was one tenth that of bone marrow mononuclear cells (9 x 10(5) cells per heart in the MNC group compared to 9 x 10(4) per heart in the SP group). These results support the hypotheses that rodent and human-bone-marrow derived side population cells are capable of acquiring a cardiac fate and that human bone-marrow-derived side population cells are superior to unfractionated bone marrow mononuclear cells in augmenting left ventricular systolic function following cryoinjury.
骨髓来源的干细胞在动物模型和临床试验中显示出心肌再生的潜力。未分离的骨髓单个核细胞（MNC）群体是一组异质细胞，已知其中包括许多干细胞群体。侧群（SP）部分的细胞具有高度分化为多种谱系的能力。在当前的研究中，我们研究了鼠和人骨髓来源的侧群细胞在心肌再生中的作用。在这些研究中，我们表明，在与新生心肌细胞共培养后以及在损伤后输送到心肌后，鼠骨髓来源的 SP 细胞表达收缩蛋白α-辅肌动蛋白。此外，在 90 天内，来源于骨髓侧群的绿色荧光蛋白阳性细胞的数量在损伤的心肌中逐渐增加。这些骨髓细胞的转录组分析显示出与未成熟心肌细胞一致的表达模式。此外，还评估了粒细胞集落刺激因子刺激的人外周血干细胞在损伤大鼠心肌内注射后的分化能力。注射后 1 个月，在大鼠心肌内均可轻易识别骨髓单核细胞和侧群细胞。这些人细胞通过免疫组织化学法确定表达人特异性肌钙蛋白 I，以及通过聚合酶链反应确定许多心脏转录物。在由于冷冻损伤导致心脏功能适度下降后，人骨髓单核细胞和人侧群细胞均增强了心脏的收缩功能。尽管使用的侧群细胞数量是骨髓单核细胞的十分之一（MNC 组每只心脏为 9×10（5）个细胞，而 SP 组每只心脏为 9×10（4）个细胞），但与骨髓单核细胞相比，注射侧群细胞后心脏功能的增强更早。这些结果支持以下假设：啮齿动物和人骨髓来源的侧群细胞能够获得心脏命运，并且在冷冻损伤后增强左心室收缩功能方面，人骨髓来源的侧群细胞优于未分离的骨髓单核细胞。
