Bone Marrow-Derived B Cells Preserve Ventricular Function After Acute Myocardial Infarction
Bone Marrow-Derived B Cells Preserve Ventricular Function After Acute Myocardial Infarction
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DOI：
10.1016/j.jcin.2009.08.010
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发表时间：
2009-10-01
影响因子：
11.3
通讯作者：
Chronos, Nicolas A. F.
中科院分区：
文献类型：
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作者：
Goodchild, Traci T.;Robinson, Keith A.;Chronos, Nicolas A. F.
目的鉴于成熟细胞在调节干细胞龛中起作用，从而调节干细胞潜能和增殖的证据，我们假设成熟的骨髓（BM）单核细胞（MNC）输注亚组分可能在促进造血干细胞或驻留干细胞诱导的梗死后心脏修复方面具有特别的效力。BM MNC输注显示出改善患者结局的前景。然而，临床数据是相互矛盾的，并证明适度的改善。方法从同基因供体大鼠骨髓中分离出干细胞（c-kit+）和成熟细胞亚群，包括髓系细胞、B细胞和T细胞。对Wistar大鼠进行基线超声心动图检查，然后进行冠状动脉结扎;将1 × 106个细胞（富集的BM MNC亚群或亚群组合）或生理盐水注射到缺血和缺血边缘区。新鲜或过夜培养后注射细胞亚群。2周后，动物接受随访超声心动图。结果与生理盐水组相比，模型组心室内径缩短率明显改善（38 +/- 3.2%）当单独新鲜注射B细胞时（44 +/-3.0%，p = 0.035），或过夜培养后（51 +/-2.9%，p < 0.001），或与c-kit+细胞培养后（44 +/-2.4%，p = 0.062）。注射后48 h，与对照组相比，B细胞减少了细胞凋亡（5.7 +/-1. 2% vs. 12.6 +/-2.0%，p = 0.005）。结论心肌内注射B细胞到缺血后早期心肌中，通过心肌细胞挽救来保护心脏功能。其他BM MNC亚型由富集的B细胞群赋予的心脏保护无效或受到抑制。（J Am科尔Cardiol Intv 2009; 2：1005-16）（c）美国心脏病学会基金会2009年
Objectives In view of evidence that mature cells play a role in modulating the stem cell niche and thereby stem cell potential and proliferation, we hypothesized that a mature bone marrow (BM) mononuclear cell (MNC) infusion subfraction may have particular potency in promoting hematopoietic or resident stem cell-induced cardiac repair post-infarction.Background Treatment of acute myocardial infarction (MI) with BM MNC infusion has shown promise for improving patient outcomes. However, clinical data are conflicting, and demonstrate modest improvements. BM MNCs consist of different subpopulations including stem cells, progenitors, and differentiated leukocytes.Methods Stem cells (c-kit+) and subsets of mature cells including myeloid lineage, B and T-cells were isolated from bone marrow harvested from isogeneic donor rats. Recipient rats had baseline echocardiography then coronary artery ligation; 1 x 10(6) cells (enriched subpopulations or combinations of subpopulations of BM MNC) or saline was injected into ischemic and ischemic border zones. Cell subpopulations were either injected fresh or after overnight culture. After 2 weeks, animals underwent follow-up echocardiography. Cardiac tissue was assayed for cardiomyocyte proliferation and apoptosis.Results Fractional ventricular diameter shortening was significantly improved compared with saline (38 +/- 3.2%) when B cells alone were injected fresh (44 +/- 3.0%, p = 0.035), or after overnight culture (51 +/- 2.9%, p < 0.001), or after culture with c-kit+ cells (44 +/- 2.4%, p = 0.062). B cells reduced apoptosis at 48 h after injection compared with control cells (5.7 +/- 1.2% vs. 12.6 +/- 2.0%, p = 0.005).Conclusions Intramyocardial injection of B cells into early post-ischemic myocardium preserved cardiac function by cardiomyocyte salvage. Other BM MNC subtypes were either ineffective or suppressed cardioprotection conferred by an enriched B cell population. (J Am Coll Cardiol Intv 2009; 2:1005-16) (c) 2009 by the American College of Cardiology Foundation