间充质干细胞移植治疗新生儿支气管肺发育不良:机遇与挑战
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摘要
支气管肺发育不良(BPD)是新生儿尤其是早产儿最常见的慢性肺部疾病,是导致早产儿预后不良的重要原因,目前临床使用的治疗手段仍然难以很好改善其预后。近年来,实验及临床研究发现间充质干细胞移植对BPD有一定疗效,可能成为未来最有希望的治疗手段。该文就间充质干细胞的特点、间充质干细胞移植治疗BPD的可能机制及临床试验的安全性和可行性,以及进一步相关临床研究面临的挑战进行阐述。[中国当代儿科杂志,2019,21(7):619-623]
Bronchopulmonary dysplasia(BPD) is one of the most common chronic lung diseases in neonates especially in preterm infants. It is also the main reason leading to a poor prognosis. The prognosis of the neonates with BPD is unsatisfactory with current treatment strategies. Recent clinical trails have found that mesenchymal stem cell(MSC) transplantation might be effective and promising for treatment of BPD in neonates. This article outlines the characteristics of MSC and the potential mechanisms of MSC transplantation for BPD in vivo,and the safety and feasibility of MSC transplantation in BPD neonates,as well as the challenges in clinical trials on MSC transplantation for treatment of BPD. [Chin J Contemp Pediatr,2019,21(7):619-623]
Bronchopulmonary dysplasia(BPD) is one of the most common chronic lung diseases in neonates especially in preterm infants. It is also the main reason leading to a poor prognosis. The prognosis of the neonates with BPD is unsatisfactory with current treatment strategies. Recent clinical trails have found that mesenchymal stem cell(MSC) transplantation might be effective and promising for treatment of BPD in neonates. This article outlines the characteristics of MSC and the potential mechanisms of MSC transplantation for BPD in vivo,and the safety and feasibility of MSC transplantation in BPD neonates,as well as the challenges in clinical trials on MSC transplantation for treatment of BPD. [Chin J Contemp Pediatr,2019,21(7):619-623]
引文
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[5]Dominici M,Le Blanc K,Mueller I,et al.Minimal criteria for defining multipotent mesenchymal stromal cells.The International Society for Cellular Therapy position statement[J].Cytotherapy,2006,8(4):315-317.
[6]Hass R,Kasper C,B?hm S,et al.Different populations and sources of human mesenchymal stem cells(MSC):a comparison of adult and neonatal tissue-derived MSC[J].Cell Commun Signal,2011,9:12.
[7]Li T,Xia M,Gao Y,et al.Human umbilical cord mesenchymal stem cells:an overview of their potential in cell-based therapy[J].Expert Opin Biol Ther,2015,15(9):1293-1306.
[8]El Omar R,Beroud J,Stoltz JF,et al.Umbilical cord m e s e n c h y m a l s t e m c e l l s:t h e n e w g o l d s t a n d a r d f o r mesenchymal stem cell-based therapies?[J].Tissue Eng Part BRev,2014,20(5):523-544.
[9]Amable PR,Teixeira MV,Carias RB,et al.Protein synthesis and secretion in human mesenchymal cells derived from bone marrow,adipose tissue and Wharton’s jelly[J].Stem Cell Res Ther,2014,5(2):53.
[10]Fung ME,Thébaud B.Stem cell-based therapy for neonatal lung disease:it is in the juice[J].Pediatr Res,2014,75(1-1):2-7.
[11]Wecht S,Rojas M.Mesenchymal stem cells in the treatment of chronic lung disease[J].Respirology,2016,21(8):1366-1375.
[12]Chang YS,Oh W,Choi SJ,et al.Human umbilical cord bloodderived mesenchymal stem cells attenuate hyperoxia-induced lung injury in neonatal rats[J].Cell Transplant,2009,18(8):869-886.
[13]Moodley Y,Ilancheran S,Samuel C,et al.Human amnion epithelial cell transplantation abrogates lung fibrosis and augments repair[J].Am J Respir Crit Care Med,2010,182(5):643-651.
[14]Sung DK,Chang YS,Ahn SY,et al.Optimal route for human umbilical cord blood-derived mesenchymal stem cell transplantation to protect against neonatal hyperoxic lung injury:gene expression profiles and histopathology[J].PLoS One,2015,10(8):e0135574.
[15]Chang YS,Choi SJ,Sung DK,et al.Intratracheal transplantation of human umbilical cord blood-derived mesenchymal stem cells dose-dependently attenuates hyperoxia-induced lung injury in neonatal rats[J].Cell Transplant,2011,20(11-12):1843-1854.
[16]van Haaften T,Byrne R,Bonnet S,et al.Airway delivery of mesenchymal stem cells prevents arrested alveolar growth in neonatal lung injury in rats[J].Am J Respir Crit Care Med,2009,180(11):1131-1142.
[17]Pierro M,Ionescu L,Montemurro T,et al.Short-term,longterm and paracrine effect of human umbilical cord-derived stem cells in lung injury prevention and repair in experimental bronchopulmonary dysplasia[J].Thorax,2013,68(5):475-484.
[18]Chang YS,Ahn SY,Yoo HS,et al.Mesenchymal stem cells for bronchopulmonary dysplasia:phase 1 dose-escalation clinical trial[J].J Pediatr,2014,164(5):966-972.
[19]Ahn SY,Chang YS,Kim JH,et al.Two-year follow-up outcomes of premature infants enrolled in the phase I trial of mesenchymal stem cells transplantation for bronchopulmonary dysplasia[J].J Pediatr,2017,185:49-54.e2.
[20]de la Fuente R,Bernad A,Garcia-Castro J,et al.Retraction:spontaneous human adult stem cell transformation[J].Cancer Res,2010,70(16):6682.
[21]Wagner W.Senescence is heterogeneous in mesenchymal stromal cells:kaleidoscopes for cellular aging[J].Cell Cycle,2010,9(15):2923-2924.
[2]张梦圆,王颖翠,何洁,等.脐带间充质干细胞治疗技术的临床研究策略[J].西南国防医药,2018,28(1):7-9.
[3]Mitsialis SA,Kourembanas S.Stem cell-based therapies for the newborn lung and brain:possibilities and challenges[J].Semin Perinatol,2016,40(3):138-151.
[4]Chang YS,Ahn SY,Sung S,et al.Stem cell therapy for neonatal disorders:prospects and challenges[J].Yonsei Med J,2017,58(2):266-271.
[5]Dominici M,Le Blanc K,Mueller I,et al.Minimal criteria for defining multipotent mesenchymal stromal cells.The International Society for Cellular Therapy position statement[J].Cytotherapy,2006,8(4):315-317.
[6]Hass R,Kasper C,B?hm S,et al.Different populations and sources of human mesenchymal stem cells(MSC):a comparison of adult and neonatal tissue-derived MSC[J].Cell Commun Signal,2011,9:12.
[7]Li T,Xia M,Gao Y,et al.Human umbilical cord mesenchymal stem cells:an overview of their potential in cell-based therapy[J].Expert Opin Biol Ther,2015,15(9):1293-1306.
[8]El Omar R,Beroud J,Stoltz JF,et al.Umbilical cord m e s e n c h y m a l s t e m c e l l s:t h e n e w g o l d s t a n d a r d f o r mesenchymal stem cell-based therapies?[J].Tissue Eng Part BRev,2014,20(5):523-544.
[9]Amable PR,Teixeira MV,Carias RB,et al.Protein synthesis and secretion in human mesenchymal cells derived from bone marrow,adipose tissue and Wharton’s jelly[J].Stem Cell Res Ther,2014,5(2):53.
[10]Fung ME,Thébaud B.Stem cell-based therapy for neonatal lung disease:it is in the juice[J].Pediatr Res,2014,75(1-1):2-7.
[11]Wecht S,Rojas M.Mesenchymal stem cells in the treatment of chronic lung disease[J].Respirology,2016,21(8):1366-1375.
[12]Chang YS,Oh W,Choi SJ,et al.Human umbilical cord bloodderived mesenchymal stem cells attenuate hyperoxia-induced lung injury in neonatal rats[J].Cell Transplant,2009,18(8):869-886.
[13]Moodley Y,Ilancheran S,Samuel C,et al.Human amnion epithelial cell transplantation abrogates lung fibrosis and augments repair[J].Am J Respir Crit Care Med,2010,182(5):643-651.
[14]Sung DK,Chang YS,Ahn SY,et al.Optimal route for human umbilical cord blood-derived mesenchymal stem cell transplantation to protect against neonatal hyperoxic lung injury:gene expression profiles and histopathology[J].PLoS One,2015,10(8):e0135574.
[15]Chang YS,Choi SJ,Sung DK,et al.Intratracheal transplantation of human umbilical cord blood-derived mesenchymal stem cells dose-dependently attenuates hyperoxia-induced lung injury in neonatal rats[J].Cell Transplant,2011,20(11-12):1843-1854.
[16]van Haaften T,Byrne R,Bonnet S,et al.Airway delivery of mesenchymal stem cells prevents arrested alveolar growth in neonatal lung injury in rats[J].Am J Respir Crit Care Med,2009,180(11):1131-1142.
[17]Pierro M,Ionescu L,Montemurro T,et al.Short-term,longterm and paracrine effect of human umbilical cord-derived stem cells in lung injury prevention and repair in experimental bronchopulmonary dysplasia[J].Thorax,2013,68(5):475-484.
[18]Chang YS,Ahn SY,Yoo HS,et al.Mesenchymal stem cells for bronchopulmonary dysplasia:phase 1 dose-escalation clinical trial[J].J Pediatr,2014,164(5):966-972.
[19]Ahn SY,Chang YS,Kim JH,et al.Two-year follow-up outcomes of premature infants enrolled in the phase I trial of mesenchymal stem cells transplantation for bronchopulmonary dysplasia[J].J Pediatr,2017,185:49-54.e2.
[20]de la Fuente R,Bernad A,Garcia-Castro J,et al.Retraction:spontaneous human adult stem cell transformation[J].Cancer Res,2010,70(16):6682.
[21]Wagner W.Senescence is heterogeneous in mesenchymal stromal cells:kaleidoscopes for cellular aging[J].Cell Cycle,2010,9(15):2923-2924.