2012年12月05日 讯 /生物谷BIOON/ --加拿大渥太华医院研究所(Ottawa Hospital Research Institute)新生儿学家Bernard Thébaud博士在一篇发表在Thorax期刊上的论文中提出了一种利用来自脐带血的干细胞来治疗一种之前被认为无法医治的疾病，即支气管肺发育不良(bronchopulmonary dysplasia, BPD)。
在加拿大和美国，BPD每年大约影响着1万名极早产新生儿(very premature newborns)。这些婴儿的肺部并没有足够地发育来维持它们，因此他们必须通过呼吸机接受氧气。然而，机械通气和氧气组合使用会损伤肺部和阻止它们的发育。此外，长期呆在新生儿重症监护室(neonatal intensive care unit)也影响着这些极早产新生儿身体其他部分(包括视网膜、肾脏和大脑)的正常发育。
在这项研究中，研究人员利用给新生大鼠供应氧气的实验提供一些非常重要的发现。他们利用新生大鼠的肺部发育来模拟在第24周出生的早产新生儿的肺部发育。在这篇论文中，他们报道了5个主要的研究发现：
(1)来自人脐带血的间充质干细胞(mesenchymal stromal cell, MSC)当注射到这些小鼠体内时能够给它们的肺部带来它们吸入氧气时产生的保护性效应。
(2)在吸入氧气两周之后，注射到小鼠体内的MSC具有修复性效应。
(3)当注射条件培养基---一种MSC产生的不含细胞的物质---而不是MSC时，研究人员发现该物资具有与MSC一样的保护性和修复性效应。
(4)当注射6个月之后，接受治疗的动物拥有更好的运动能力，而且给肺部带来持续性的益处。
(5)MSC给正常大鼠的长期健康并不带来不良影响。关于干细胞的一个担忧就是它们除了促进细胞生长之外，可能也促进癌症生长。为了解决这个问题，Thébaud博士给事先未吸入氧气的对照组大鼠注射MSC。当注射6个月之后，他发现这些动物仍然保持正常和健康。
在未来两年之内，Thébaud博士想给20名病人开展前瞻性研究以便验证这种干细胞疗法是可行的和安全的。在未来四年之内，他想开展一项随机对照试验。他自信人们将能够开发出一种治疗方法来治疗BPD。(生物谷Bioon.com)
doi: 10.1136/thoraxjnl-2012-202323
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Short-term, long-term and paracrine effect of human umbilical cord-derived stem cells in lung injury prevention and repair in experimental bronchopulmonary dysplasia
Maria Pierro1,2, Lavinia Ionescu1, Tiziana Montemurro3, Arul Vadivel1, Gaia Weissmann2, Gavin Oudit4, Derek Emery5, Sreedhar Bodiga4, Farah Eaton1, Bruno Péault6, Fabio Mosca2, Lorenza Lazzari3, Bernard Thébaud7
Background Bronchopulmonary dysplasia (BPD) remains a main complication of extreme prematurity and currently lacks efficient treatment. Rat bone marrow-derived mesenchymal stem cells (MSC) prevent lung injury in an oxygen-induced model of BPD. Human cord is an advantageous source of stem cells that is especially appealing for the treatment of neonatal diseases. The therapeutic benefit after established lung injury and long-term safety of cord-derived stem cells is unknown.
Methods Human cord-derived perivascular cells (PCs) or cord blood-derived MSCs were delivered prophylactically or after established alveolar injury into the airways of newborn rats exposed to hyperoxia, a well-established BPD model.
Results Rat pups exposed to hyperoxia showed the characteristic arrest in alveolar growth with air space enlargement and loss of lung capillaries. PCs and MSCs partially prevented and rescued lung function and structure. Despite therapeutic benefit, cell engraftment was low, suggesting that PCs and MSCs act via a paracrine effect. Accordingly, cell free-derived conditioned media from PCs and MSCs also exerted therapeutic benefit when used either prophylactically or therapeutically. Finally, long-term (6 months) assessment of stem cell or conditioned media therapy showed no adverse lung effects of either strategy, with persistent improvement in exercise capacity and lung structure.
Conclusions Human umbilical cord-derived PCs and MSCs exert short- and long-term therapeutic benefit without adverse lung effects in this experimental model and offer new therapeutic options for lung diseases characterised by alveolar damage.
