Derval Nicolas, Barandon Laurent, Dufourcq Pascale, Leroux Lionel, Lamazière Jean-Marie Daniel, Daret Danièle, Couffinhal Thierry, Duplàa Cécile
Cardiovascular Surgery and Cardiology Department, Hôpital Haut-Lévêque, Avenue de Magellan, Pessac 33604, France.
Eur J Cardiothorac Surg. 2008 Aug;34(2):248-54. doi: 10.1016/j.ejcts.2008.03.058. Epub 2008 May 23.
To assess, using an in vivo engraftment strategy combining bone marrow cell (BMC) transplantation and tissue cardiomyoplasty, the functional outcome of distinct vascular progenitor cell therapy (endothelial progenitor (EPC) and mesenchymal stem (MSC) cells) at distance of myocardium infarction (MI). The study was also designed to test whether scaffold mixing progenitors with unfractionated BMC could improve progenitor recruitment in the damaged myocardium.
To track engrafted progenitor cells in vivo, cultured murine MSC and EPC were transduced with eGFP lentiviruses. Thirty days after cryogenical induction of MI, C57BL/6J mice were randomized to receive muscle patch placement coated or not (control group), labeled EPC or MSC mixed to the ration of 1:10, or not with unfractionated BMC. Two weeks after transplantation, cardiac function was recorded and heart sections were examined to detect GFP-labeled progenitor cells and analyze cell differentiation.
This study showed that either type of mono cell therapy improved angiogenesis and cell survival in the scar but only MSC exhibited the capacity to invade the scar. We found no evidence of myocardial or vascular regeneration from progenitor cells. Engraftment of the progenitors/unfractionated BMC mix increased repopulation and thickness of the scar.
Combined therapy with unfractionated BMC and expanded MSC appeared thus promising for scar repopulation.
采用骨髓细胞(BMC)移植与组织心肌成形术相结合的体内植入策略,评估不同血管祖细胞疗法(内皮祖细胞(EPC)和间充质干细胞(MSC))在心肌梗死(MI)区域的功能结局。该研究还旨在测试将祖细胞与未分级的BMC混合使用支架是否能改善受损心肌中祖细胞的募集。
为了在体内追踪植入的祖细胞,用eGFP慢病毒转导培养的小鼠MSC和EPC。在MI冷冻诱导30天后,将C57BL/6J小鼠随机分组,分别接受涂有或未涂有(对照组)标记的EPC或MSC(按1:10比例混合)的肌肉贴片植入,或与未分级的BMC混合或不混合。移植两周后,记录心脏功能,并检查心脏切片以检测GFP标记的祖细胞并分析细胞分化。
本研究表明,两种单细胞疗法均能改善瘢痕组织中的血管生成和细胞存活,但只有MSC表现出侵入瘢痕的能力。我们没有发现祖细胞促进心肌或血管再生的证据。祖细胞/未分级BMC混合物的植入增加了瘢痕的再填充和厚度。
因此,未分级的BMC与扩增的MSC联合治疗在瘢痕再填充方面似乎很有前景。