Department of Anatomy and Physiology, Kansas State University, Coles Hall, room 105, Manhattan, KS 66506, USA.
Curr Stem Cell Res Ther. 2013 Jan;8(1):46-59. doi: 10.2174/1574888x11308010007.
The therapeutic effect of mesenchymal stromal cells (MSCs) following myocardial infarction (MI) is small. This may be due to differences in cellular sources and donor age, route of administration, in vitro cellular manipulations and the short time course of follow up in many animal studies. Here, we compared MSCs from two different sources (adult bone marrow or Wharton's jelly from umbilical cord) for their long-term therapeutic effect following MI in a rat model to evaluate the effect of donor age. MSCs (or control infusions) were given intravenously 24-48 hr after myocardial ischemia (MI) induced by coronary artery ligation. Cardiac function was assessed by ultrasound at time points starting from before MSC infusion through 68 weeks after MI. A significant improvement in ejection fraction was seen in animals that received MSCs in time points 25 to 31 wks after treatment (p < 0.01). These results support previous work that show that MSCs can cause improvement in cardiac function and extend that work by showing that the beneficial effects are durable. To investigate MSCs' cardiac differentiation potential, Wharton's jelly MSCs were co-cultured with fetal or adult bone-derived marrow MSCs. When Wharton's jelly MSCs were co-cultured with fetal MSCs, and not with adult MSCs, myotube structures were observed in two-three days and spontaneous contractions (beating) cells were observed in fiveseven days. The beating structures formed a functional syncytium indicated by coordinated contractions (beating) of independent nodes. Taken together, these results suggest that MSCs given 24-48 hr after MI have a significant and durable beneficial effect more than 25 weeks after MI and that MSC treatment can home to damaged tissue and improve heart function after intravenous infusion 24-48 hrs after MI, and that WJCs may be a useful source for off-the-shelf cellular therapy for MI.
间充质干细胞（MSCs）在心肌梗死（MI）后的治疗效果较小。这可能是由于细胞来源和供体年龄、给药途径、体外细胞操作以及许多动物研究的随访时间短的差异所致。在这里，我们比较了两种不同来源（成人骨髓或脐带华通氏胶）的 MSCs 在大鼠 MI 模型中的长期治疗效果，以评估供体年龄的影响。MSCs（或对照输注）在冠状动脉结扎引起心肌缺血（MI）后 24-48 小时内静脉内给予。在 MSC 输注前开始，通过 MI 后 68 周的时间点，通过超声评估心脏功能。在治疗后 25 至 31 周的时间点，接受 MSCs 的动物的射血分数明显改善（p < 0.01）。这些结果支持先前的工作，表明 MSCs 可以改善心脏功能，并通过显示有益效果持久来扩展该工作。为了研究 MSCs 的心脏分化潜力，将华通氏胶 MSCs 与胎儿或成人骨髓 MSCs 共培养。当华通氏胶 MSCs 与胎儿 MSCs 共培养而不是与成人 MSCs 共培养时，在两到三天内观察到肌管结构，并且在五到七天内观察到自发收缩（搏动）细胞。搏动结构形成了一个功能性合胞体，由独立节点的协调收缩（搏动）表示。总之，这些结果表明，在 MI 后 24-48 小时给予 MSCs 具有显著且持久的有益效果，超过 MI 后 25 周，并且 MSC 治疗可以在 MI 后 24-48 小时静脉内输注后归巢到受损组织并改善心脏功能，并且 WJCs 可能是 MI 现货细胞治疗的有用来源。
