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Pediatrics -- eLetters for Popova et al., 126 (5) 1127-1133





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               days after parental written informed consent.

                     eLetters to:
               All procedures for ucMSC processing complied with good
               manufacturing practices (GMPs) requirements and the   BPD
                           Articles: grade [10,11]. The MSCs
               ucMSCs are clinical
                                                                                            eLetters: Submit
                           Antonia P. Popova, Paul D. Bozyk, J. Kelley Bentley, Marisa J. Linn,
               suspension in 6 ml (3x 10^6 cells per kg of the                            a response to this
                           Adam M. Goldsmith, Robert E. Schumacher, Gary M. Weiner, Amy
               patient's weight) were divided into 4 aliquots for 4   嚴重支氣管肺發育不全
                                                                                          article
                           G. Filbrun, and Marc B. Hershenson
               positions as the way of giving surfactant at age of 168
                                 Isolation of Tracheal Aspirate Mesenchymal Stromal
               days and weighed 2680 g. Bronchoalveolar lavages
            臍帶間質幹細胞(MSC)治療嚴重支氣管肺發育不全,在60天內即
                                 Cells Predicts Bronchopulmonary Dysplasia
               (BAL) were performed before and after the MSC
                                 Pediatrics 2010; 126: e1127-e1133 [Abstract] [Full text] [PDF]
            有明顯的改善成效
               treatment. The concentrations of proinflammatory
               cytokines including interleukin-6 (IL-6), IL-8, and tumor
               necrosis factor (TNF)-alpha were measured using
                     eLetters published:
            24 週大的她,只有 800 公克,出生後 168 天體重才 2680 公克,兩位醫生決定
               commercial enzyme- linked immunosorbent assay
            進行氣管內間質幹細胞輸注治療:
               (ELISA) kits from Research and Diagnostic Systems
                              Umbilical Cord-derived Mesenchymal Stem Cells for Severe
            ˙ 60 天 - 發育不全的嚴重程度明顯改善
               (Minneapolis, MN, USA). Echocardiographic assessment
                           Bronchpulmonary Dysplasia
               of pulmonary arterial pressure (PAP) was performed as
            ˙ 73 天 - 她可以自行呼吸
                                 Bai-Horng Su, Kang-Hsi Wu, Hsiang-Yu Lin, Ming-Hsia Lin, Ching-Tien Peng,
               our previous report [12] on the day BAL was performed.
                                 Chris Tsai, (Dr. Su and Dr. Wu are contributed equally to this work)   (21
            ˙ 7 個月後 - 健康狀況非常良好
               The time to peak velocity (TPV) and right ventricular
                                 January 2011)
               ejection time (RVET) were measured and the heart rate-
               corrected TPV/RVET(c) is inversely related to PAP. The
               patient did not undergo treatment for pulmonary
               hypertension, such as sildenefil or prostacyclin, prior to
               MSC treatment. The mean values of oxygenation, mean
                      Umbilical Cord-derived Mesenchymal Stem
               airway pressure and oxygenation index were also                     21 January
                      Cells for Severe Bronchpulmonary Dysplasia
               recorded on the days when lavages were performed.                         2011
               The severity score of BPD on the chest radiographs was
               graded [13].
                      Bai-Horng Su,
                      Professor of Pediatrics    Popova et al presented a study on the tracheal aspirates
                      China Medical University   from 84 premature infants requiring mechanical
                                           ventilation for respiratory distress and concluded that
               Dramatic reduction in FiO2 requirement, improvement
                      Hospital and College of
                      Medicine, China Medical
                                           isolation of lung mesenchymal stem cells (MSCs) within
               of PaO2, fall in oxygenation index and significant
                      University,Taichung,Taiwa
               improvement of PAP as evidenced by TPV/RVET(c)
                                           the first week of life predicts the development of
                      n,
               followed by extubation on day 7 after treatment is
                                           bronchpulmonary dysplasia (BPD) [1]. Their results
                      Kang-Hsi Wu, Hsiang-Yu
                      Lin, Ming-Hsia Lin, Ching-
                                           revealed that MSC isolation negatively correlated with
               noted. The proinflammatory cytokine levels in lavage
                      Tien Peng, Chris Tsai,
                                           gestational age at birth. There was also a significant
               fluid reduced progressively by day 7 to less than one
                      (Dr. Su and Dr. Wu are
                                           positive correlation between postnatal age and MSC
                      contributed equally to
               tenth of the level before treatment. The clinical
                                           yield. The history of maternal chorioamnionitis was
                      this work)
               improvement and reduced PAP were significantly related
               with the reduced proinflammatory cytokines levels. The
               severity score of BPD improved disproportionately less
               than the reduction in proinflammatory cytokine levels
               initially, but much improved by 60 days after treatment.
                  http://pediatrics.aappublications.org/cgi/eletters/126/5/e1127
               The patient is breathing room air 73 days after MSC                                       2011/1/22
               treatment, and now is well 7 months after treatment.
               Inflammation may predispose the premature newborn
               to pulmonary hypertension [14]. Previous animal
               studies have shown that intratracheal administration of
               MSCs ameliorated pulmonary hypertension [15]. We
               have demonstrated clinically that intratracheal MSC are
            資料來源:第一期臨床研究  NCT01207869 Pediatrics 2010; 126: e1127-e1133                                9
               capable of reducing PAP as evidenced by
               echocardiography in this patient. The dramatic clinical
               improvement and the disproportionately less initial
               improvement in the x- ray implicate that the initial
               beneficial effects of ucMSC treatment might be
               mediated mainly by its anti-inflammatory effects. We
               assume that the improvement of chest x-ray 60 days
               after treatment is due to the late effect of ucMSC
               treatment.
               In summary, the overall effects attributed to MSC
               treatment in this patient could be potentially derived
               from the reduced pulmonary inflammation and hence
               the reduced pulmonary hypertension. The draw back is
 http://pediatrics.aappublications.org/cgi/eletters/126/5/e1127                 2011/1/22
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