Ottawa Hospital Research Institute, Sinclair Centre for Regenerative Medicine, Ottawa, Ontario, Canada.
Division of Neonatology, Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
Pediatr Res. 2018 Jan;83(1-2):291-297. doi: 10.1038/pr.2017.232. Epub 2017 Oct 18.
Lung diseases remain one of the main causes of morbidity and mortality in neonates. Cell therapy and regenerative medicine have the potential to revolutionize the management of life-threatening and debilitating lung diseases that currently lack effective treatments. Over the past decade, the repair capabilities of stem/progenitor cells have been harnessed to prevent/rescue lung damage in experimental neonatal lung diseases. Mesenchymal stromal cells and amnion epithelial cells exert pleiotropic effects and represent ideal therapeutic cells for bronchopulmonary dysplasia, a multifactorial disease. Endothelial progenitor cells are optimally suited to promote lung vascular growth and attenuate pulmonary hypertension in infants with congenital diaphragmatic hernia or a vascular bronchopulmonary dysplasia phenotype. Induced pluripotent stem cells (iPSCs) are one of the most exciting breakthroughs of the past decade. Patient-specific iPSCs can be derived from somatic cells and differentiated into any cell type. iPSCs can be capitalized upon to develop personalized regenerative cell products for surfactant protein deficiencies-lethal lung disorders without treatment-that affect a single gene in a single cell type and thus lend themselves to phenotype-specific cell replacement. While the clinical translation has begun, more needs to be learned about the biology of these repair cells to make this translation successful.
肺部疾病仍然是导致新生儿发病和死亡的主要原因之一。细胞疗法和再生医学有可能彻底改变目前缺乏有效治疗方法的危及生命和使人衰弱的肺部疾病的治疗方法。在过去的十年中，已经利用干细胞/祖细胞的修复能力来预防/挽救实验性新生儿肺部疾病中的肺损伤。间充质基质细胞和羊膜上皮细胞发挥多效作用，是支气管肺发育不良这一多种因素疾病的理想治疗细胞。内皮祖细胞最适合促进肺血管生长并减轻患有先天性膈疝或血管性支气管肺发育不良表型的婴儿的肺动脉高压。诱导多能干细胞（iPSCs）是过去十年中最令人兴奋的突破之一。可以从体细胞中获得患者特异性 iPSCs 并将其分化为任何细胞类型。可以利用 iPSCs 开发针对表面活性剂蛋白缺乏症（致命肺部疾病，无治疗方法）的个性化再生细胞产品，这些疾病仅影响单一细胞类型中的单个基因，因此适合特定表型的细胞替代。虽然临床转化已经开始，但需要进一步了解这些修复细胞的生物学特性，以使这种转化取得成功。
