AC Therapeutics, Inc., Norcross, Georgia, USA.
JACC Cardiovasc Interv. 2009 Oct;2(10):1005-16. doi: 10.1016/j.jcin.2009.08.010.
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.
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.
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.
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).
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.
鉴于成熟细胞在调节干细胞生态位，从而调节干细胞潜能和增殖方面发挥作用的证据，我们假设骨髓（BM）单核细胞（MNC）输注亚群中的一个成熟部分可能在促进造血或驻留干细胞诱导的梗塞后心脏修复方面具有特殊功效。
用 BM MNC 输注治疗急性心肌梗死（MI）已显示出改善患者预后的希望。然而，临床数据存在矛盾，并表明改善效果不大。BM MNC 由不同的亚群组成，包括干细胞、祖细胞和分化的白细胞。
从同种异体供体大鼠的骨髓中分离出干细胞（c-kit+）和包括髓系、B 和 T 细胞在内的成熟细胞亚群。受体大鼠进行基线超声心动图检查，然后结扎冠状动脉；将 1x10(6)个细胞（BM MNC 的富集亚群或亚群组合）或生理盐水注入缺血和缺血边界区。细胞亚群要么新鲜注射，要么过夜培养后注射。2 周后，动物进行随访超声心动图检查。对心脏组织进行心肌细胞增殖和凋亡检测。
与生理盐水组（38 +/- 3.2%）相比，单独注射 B 细胞（新鲜注射 44 +/- 3.0%，p = 0.035）或过夜培养后注射（51 +/- 2.9%，p < 0.001）或与 c-kit+细胞共培养后注射（44 +/- 2.4%，p = 0.062），心室短轴缩短分数明显改善。与对照细胞相比，注射后 48 小时 B 细胞减少了凋亡（5.7 +/- 1.2% vs. 12.6 +/- 2.0%，p = 0.005）。
在早期缺血后心肌内注射 B 细胞通过心肌细胞挽救来保存心脏功能。其他 BM MNC 亚型要么无效，要么抑制了富含 B 细胞群体的心脏保护作用。
