Thompson Richard B, van den Bos Ewout J, Davis Bryce H, Morimoto Yoshihisa, Craig Damian, Sutton Brad S, Glower Donald D, Taylor Doris A
Department of Surgery, Duke University Medical Center, Durham, NC, USA.
J Heart Lung Transplant. 2005 Feb;24(2):205-14. doi: 10.1016/j.healun.2003.10.021.
Pre-clinical and clinical studies suggest that transplantation of bone marrow-derived stem cells can improve global cardiac function. However, no quantitative assessment of regional systolic contraction and correlation with phenotype has been made. Therefore, we used our model of cryoinfarcted rabbit myocardium for intracardiac transplantation of a mixed population of bone marrow-derived cells and assessed both regional function and myogenic conversion of the cells.
Nineteen New Zealand white rabbits underwent cryoinjury of the left ventricle. Autologous bone marrow (BM) cells were expanded in vitro. After 2 weeks, either 1 x 10(8) mixed BM-derived progenitor cells (BM group, n = 11) or vehicle (control group, n = 8) were injected into the cryoinjured region. Regional systolic function was measured using micromanometry and sonomicrometry before and 4 weeks after cell injection; cell phenotype was evaluated histologically.
All animals in the BM group significantly improved both systolic shortening (0.11 +/- 0.7 vs -0.05 +/- 0.05 mm in the control group, p < 0.05) and regional stroke work when compared with control (9.6 +/- 2.4 vs -1.2 +/- 1.2 mm . mm Hg, p < 0.003). In addition, the BM group had improved global diastolic function, as measured by minimum dP/dt and end-diastolic pressure. On histologic assessment, BM cells differentiated toward a myogenic phenotype.
Transplanting a mixed population of marrow-derived cells that can adopt a myogenic phenotype improves regional contractility and diastolic relaxation after myocardial infarction.
临床前和临床研究表明,骨髓源性干细胞移植可改善整体心脏功能。然而,尚未对局部收缩功能进行定量评估,也未研究其与细胞表型的相关性。因此,我们利用冷冻梗死兔心肌模型进行心脏内骨髓源性细胞混合群体的移植,并评估细胞的局部功能和肌源性转化。
19只新西兰白兔接受左心室冷冻损伤。自体骨髓细胞在体外扩增。2周后,将1×10(8)个混合的骨髓源性祖细胞(骨髓组,n = 11)或赋形剂(对照组,n = 8)注入冷冻损伤区域。在细胞注射前和注射后4周,使用微测压法和超声微测法测量局部收缩功能;通过组织学评估细胞表型。
与对照组相比,骨髓组所有动物的收缩期缩短(0.11±0.7 vs对照组的-0.05±0.05 mm,p < 0.05)和局部每搏功均显著改善(9.6±2.4 vs -1.2±1.2 mm·mmHg,p < 0.003)。此外,通过最小dP/dt和舒张末期压力测量,骨髓组的整体舒张功能也有所改善。组织学评估显示,骨髓细胞向肌源性表型分化。
移植可呈现肌源性表型的骨髓源性细胞混合群体可改善心肌梗死后的局部收缩性和舒张期松弛。