2012年12月05日 訊 /生物谷BIOON/ --加拿大渥太華醫(yī)院研究所(Ottawa Hospital Research Institute)新生兒學(xué)家Bernard Thébaud博士在一篇發(fā)表在Thorax期刊上的論文中提出了一種利用來自臍帶血的干細(xì)胞來治療一種之前被認(rèn)為無法醫(yī)治的疾病,，即支氣管肺發(fā)育不良(bronchopulmonary dysplasia, BPD)。
在加拿大和美國,，BPD每年大約影響著1萬名極早產(chǎn)新生兒(very premature newborns),。這些嬰兒的肺部并沒有足夠地發(fā)育來維持它們，因此他們必須通過呼吸機(jī)接受氧氣,。然而,，機(jī)械通氣和氧氣組合使用會(huì)損傷肺部和阻止它們的發(fā)育。此外,，長期呆在新生兒重癥監(jiān)護(hù)室(neonatal intensive care unit)也影響著這些極早產(chǎn)新生兒身體其他部分(包括視網(wǎng)膜,、腎臟和大腦)的正常發(fā)育。
在這項(xiàng)研究中,，研究人員利用給新生大鼠供應(yīng)氧氣的實(shí)驗(yàn)提供一些非常重要的發(fā)現(xiàn)。他們利用新生大鼠的肺部發(fā)育來模擬在第24周出生的早產(chǎn)新生兒的肺部發(fā)育,。在這篇論文中,，他們報(bào)道了5個(gè)主要的研究發(fā)現(xiàn)：
(1)來自人臍帶血的間充質(zhì)干細(xì)胞(mesenchymal stromal cell, MSC)當(dāng)注射到這些小鼠體內(nèi)時(shí)能夠給它們的肺部帶來它們吸入氧氣時(shí)產(chǎn)生的保護(hù)性效應(yīng)。
(2)在吸入氧氣兩周之后,，注射到小鼠體內(nèi)的MSC具有修復(fù)性效應(yīng),。
(3)當(dāng)注射條件培養(yǎng)基---一種MSC產(chǎn)生的不含細(xì)胞的物質(zhì)---而不是MSC時(shí)，研究人員發(fā)現(xiàn)該物資具有與MSC一樣的保護(hù)性和修復(fù)性效應(yīng),。
(4)當(dāng)注射6個(gè)月之后,，接受治療的動(dòng)物擁有更好的運(yùn)動(dòng)能力，而且給肺部帶來持續(xù)性的益處,。
(5)MSC給正常大鼠的長期健康并不帶來不良影響,。關(guān)于干細(xì)胞的一個(gè)擔(dān)憂就是它們除了促進(jìn)細(xì)胞生長之外，可能也促進(jìn)癌癥生長。為了解決這個(gè)問題,，Thébaud博士給事先未吸入氧氣的對(duì)照組大鼠注射MSC,。當(dāng)注射6個(gè)月之后，他發(fā)現(xiàn)這些動(dòng)物仍然保持正常和健康,。
在未來兩年之內(nèi),，Thébaud博士想給20名病人開展前瞻性研究以便驗(yàn)證這種干細(xì)胞療法是可行的和安全的。在未來四年之內(nèi),，他想開展一項(xiàng)隨機(jī)對(duì)照試驗(yàn),。他自信人們將能夠開發(fā)出一種治療方法來治療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.
