Wolf David, Reinhard Adrian, Seckinger Anja, Gross Lisa, Katus Hugo A, Hansen Alexander
Department of Cardiology, University of Heidelberg, Germany.
Scand Cardiovasc J. 2009 Feb;43(1):39-45. doi: 10.1080/14017430802100280.
Intravenous delivery of mesenchymal stem cells (MSCs) is an attractive approach for regeneration of infarcted myocardium. However, its efficacy is not well-defined in large animals.
Pigs (n =8) received intravenously autologous, allogeneic porcine or human MSCs (1 x 10(6) per kg bodyweight) labeled with fluorescent dye 48 hours post proximal LAD occlusion. Infarct size, histology and myocardial function were assessed 4 weeks later.
Labeled MSCs migrated in the peri-infarct region resulting in improved myocardial function. Infarct size was larger in the control group (32+/-7%) compared to autologous (19+/-7%, p =0.008), allogeneic (24+/-4%, p =0.01) and human MSCs (26+/-5%, p =0.03). Fractional area shortening significantly increased after 4 weeks in pigs receiving autologous MSCs (34+/-7%, p =0.001), allogeneic MSCs (28+/-2%, p =0.004) and human MSCs (24+/-5%, p =0.027), but was lower in the control group (23+/-3%, n.s.). However, substantial callus formation and a non-malignant cardiac "tumor" containing mesenchymal tissue was observed in one animal treated with human MSCs.
Intravenously administered MSCs prevent pathologic remodeling and scar formation but bare potential risks from inflammatory-related products.
静脉输注间充质干细胞（MSCs）是梗死心肌再生的一种有吸引力的方法。然而，其在大型动物中的疗效尚未明确界定。
猪（n = 8）在左前降支近端闭塞48小时后静脉注射自体、同种异体猪或人MSCs（每千克体重1×10⁶个），并用荧光染料标记。4周后评估梗死面积、组织学和心肌功能。
标记的MSCs迁移至梗死周边区域，从而改善心肌功能。与自体MSCs组（19±7%，p = 0.008）、同种异体MSCs组（24±4%，p = 0.01）和人MSCs组（26±5%，p = 0.03）相比，对照组的梗死面积更大（32±7%）。接受自体MSCs的猪在4周后，其节段面积缩短率显著增加（34±7%，p = 0.001），接受同种异体MSCs的猪节段面积缩短率为（28±2%，p = 0.004），接受人MSCs的猪节段面积缩短率为（24±5%，p = 0.027），而对照组的节段面积缩短率较低（23±3%，无统计学意义）。然而，在用人类MSCs治疗的一只动物中观察到大量骨痂形成和一个含有间充质组织的非恶性心脏“肿瘤”。
静脉注射MSCs可预防病理重塑和瘢痕形成，但存在与炎症相关产物带来的潜在风险。
