Laube Mandy, Stolzing Alexandra, Thome Ulrich H, Fabian Claire
Center for Pediatric Research Leipzig, Hospital for Children & Adolescents, Division of Neonatology, University of Leipzig, Leipzig, Germany.
Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany; Loughborough University, Wolfson School of Mechanical and Manufacturing Engineering, Centre for Biological Engineering, Loughborough, UK.
Int J Biochem Cell Biol. 2016 May;74:18-32. doi: 10.1016/j.biocel.2016.02.023. Epub 2016 Feb 27.
Preterm infants frequently suffer from pulmonary complications resulting in significant morbidity and mortality. Physiological and structural lung immaturity impairs perinatal lung transition to air breathing resulting in respiratory distress. Mechanical ventilation and oxygen supplementation ensure sufficient oxygen supply but enhance inflammatory processes which might lead to the establishment of a chronic lung disease called bronchopulmonary dysplasia (BPD). Current therapeutic options to prevent or treat BPD are limited and have salient side effects, highlighting the need for new therapeutic approaches. Mesenchymal stem cells (MSCs) have demonstrated therapeutic potential in animal models of BPD. This review focuses on MSC-based therapeutic approaches to treat pulmonary complications and critically compares results obtained in BPD models. Thereby bottlenecks in the translational systems are identified that are preventing progress in combating BPD. Notably, current animal models closely resemble the so-called "old" BPD with profound inflammation and injury, whereas clinical improvements shifted disease pathology towards a "new" BPD in which arrest of lung maturation predominates. Future studies need to evaluate the utility of MSC-based therapies in animal models resembling the "new" BPD though promising in vitro evidence suggests that MSCs do possess the potential to stimulate lung maturation. Furthermore, we address the mode-of-action of MSC-based therapies with regard to lung development and inflammation/fibrosis. Their therapeutic efficacy is mainly attributed to an enhancement of regeneration and immunomodulation due to paracrine effects. In addition, we discuss current improvement strategies by genetic modifications or precondition of MSCs to enhance their therapeutic efficacy which could also prove beneficial for BPD therapies.
早产儿经常遭受肺部并发症，导致严重的发病率和死亡率。生理和结构上的肺不成熟会损害围产期肺向空气呼吸的转变，从而导致呼吸窘迫。机械通气和氧气补充可确保充足的氧气供应，但会加剧炎症过程，这可能导致一种称为支气管肺发育不良（BPD）的慢性肺病的发生。目前预防或治疗BPD的治疗选择有限且有明显的副作用，这凸显了对新治疗方法的需求。间充质干细胞（MSCs）已在BPD动物模型中显示出治疗潜力。本综述重点关注基于MSCs的治疗方法来治疗肺部并发症，并批判性地比较在BPD模型中获得的结果。从而确定了转化系统中的瓶颈，这些瓶颈阻碍了对抗BPD的进展。值得注意的是，目前的动物模型与具有严重炎症和损伤的所谓“旧”BPD非常相似，而临床改善使疾病病理转向以肺成熟停滞为主的“新”BPD。未来的研究需要评估基于MSCs的疗法在类似于“新”BPD的动物模型中的效用，尽管有前景的体外证据表明MSCs确实具有刺激肺成熟的潜力。此外，我们探讨了基于MSCs的疗法在肺发育和炎症/纤维化方面的作用机制。它们的治疗效果主要归因于旁分泌效应增强了再生和免疫调节。此外，我们讨论了目前通过基因修饰或MSCs预处理来提高其治疗效果的改进策略，这也可能对BPD治疗有益。
