Adipose stem cell secretome markedly improves rodent heart and human induced pluripotent stem cell-derived cardiomyocyte recovery from cardioplegic transport solution exposure.
Adipose stem cell secretome markedly improves rodent heart and human induced pluripotent stem cell-derived cardiomyocyte recovery from cardioplegic transport solution exposure.
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脂肪干细胞分泌明显改善了啮齿动物心脏和人类诱导的多能干细胞衍生的心肌细胞从心脏倍毛转运溶液暴露中恢复。
DOI：
10.1002/stem.3296
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
March KL
中科院分区：
文献类型：
--
作者：
Ellis BW;Traktuev DO;Merfeld-Clauss S;Can UI;Wang M;Bergeron R;Zorlutuna P;March KL
心脏移植是终末期器官衰竭的一种挽救生命的治疗方法。器官在运输过程中的退化限制了4小时的储存，限制了心脏的可用性。改善器官损伤的方法可以增加可接受移植的心脏数量。先前的研究表明，脂肪源性干/基质细胞分泌组（ASC-S）在体内从缺血后损伤中拯救组织。该研究测试了ASC-S是否保留了暴露于器官运输和移植条件下的小鼠心脏和人类iPS衍生心肌细胞（iCM）的功能。将心脏置于冷的威斯康星州大学（UW）心脏停搏液± ASC-S中6小时，然后使用Langendorff技术进行分析。平行地，当在冷心脏停搏期间或之后提供时，检查ASC-S对从UW溶液中回收iCM的影响。暴露于UW的心脏和iCM的收缩活动恶化，并引起细胞凋亡，恶化iCM作为曝光时间的函数，这些都得到改善，增加ASC-S。在分泌组产生之前，SOD 3和过氧化氢酶表达的沉默损害了ASC-S心肌细胞保护作用。开发了一种新的体外iCM模型，以补充啮齿动物心脏模型，评估改善心脏保存方法的功效。ASC-S在iCM上与冷心脏停搏液一起或在冷心脏停搏液之后显示出强的心脏保护活性。这种作用与ASC-S介导的ROS细胞清除有关。ASC-S对iCM功能暂时恢复的影响支持了通过用ASC-S增加心脏停搏运输溶液来延长心脏储存的可能性，从而扩大了用于移植的心脏库。ASC-S的加入改善了UW溶液的损伤作用。储存在补充有ASC-S的UW中的小鼠心脏表现出离体存活率增加。在体外hiPSC衍生的心肌细胞中观察到这种相同的现象，当在UW孵育期间或之后立即用ASC-S处理时，细胞显示出增加的存活和功能。
Heart transplantation is a life-saving therapy for end-stage organ failure. Organ deterioration during transportation limits storage to 4 hours, limiting hearts available. Approaches ameliorating organ damage could increase the number of hearts acceptable for transplantation. Prior studies show that adipose-derived stem/stromal cell secretome (ASC-S) rescues tissues from post-ischemic damage in vivo. The study tested whether ASC-S preserved the function of mouse hearts and human iPS-derived cardiomyocytes (iCM) exposed to organ transportation and transplantation conditions. Hearts were subjected to cold University of Wisconsin (UW) cardioplegic solution ± ASC-S for 6 hours followed by analysis using the Langendorff technique. In parallel, the effects of ASC-S on the recovery of iCM from UW solution was examined when provided either during or after cold cardioplegia. Exposure of hearts and iCM to UW deteriorated contractile activity and caused cell apoptosis, worsening in iCM as a function of exposure time; these were ameliorated by augmenting with ASC-S. Silencing of SOD3 and catalase expression prior to secretome generation compromised the ASC-S cardiomyocyte-protective effects. A novel in vitro iCM model was developed to complement a rodent heart model in assessing efficacy of approaches to improve cardiac preservation. ASC-S displays strong cardioprotective activity on iCM either with or following cold cardioplegia. This effect is associated with ASC-S mediated cellular clearance of ROS. The effect of ASC-S on the temporal recovery of iCM function supports the possibility of lengthening heart storage by augmenting cardioplegic transport solution with ASC-S, expanding the pool of hearts for transplantation. The damaging effects of UW solution are ameliorated by the inclusion of ASC-S. Mouse hearts stored in UW supplemented with ASC-S demonstrated increased survivability ex vivo. This same phenomenon was observed in hiPSC derived cardiomyocytes in vitro with cells demonstrating increased survival and functionality when treated with ASC-S either during or immediately following UW incubation.
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脂肪干细胞条件培养基延长肌萎缩侧索硬化症小鼠模型的存活时间
影响因子：
4.6
作者：
Fontanilla CV;Gu H;Liu Q;Zhu TZ;Zhou C;Johnstone BH;March KL;Pascuzzi RM;Farlow MR;Du Y
通讯作者：
Du Y
影响因子：
3.2
作者：
Ellis, Bradley W.;Acun, Aylin;Zorlutuna, Pinar
通讯作者：
Zorlutuna, Pinar
DOI：
10.1152/ajpcell.2001.281.3.c758
发表时间：
2001-09-01
影响因子：
5.5
作者：
Hegge, JO;Southard, JH;Haworth, RA
通讯作者：
Haworth, RA
影响因子：
46.9
作者：
Giwa S;Lewis JK;Alvarez L;Langer R;Roth AE;Church GM;Markmann JF;Sachs DH;Chandraker A;Wertheim JA;Rothblatt M;Boyden ES;Eidbo E;Lee WPA;Pomahac B;Brandacher G;Weinstock DM;Elliott G;Nelson D;Acker JP;Uygun K;Schmalz B;Weegman BP;Tocchio A;Fahy GM;Storey KB;Rubinsky B;Bischof J;Elliott JAW;Woodruff TK;Morris GJ;Demirci U;Brockbank KGM;Woods EJ;Ben RN;Baust JG;Gao D;Fuller B;Rabin Y;Kravitz DC;Taylor MJ;Toner M
通讯作者：
Toner M
影响因子：
4.4
作者：
Li, Xin;Arslan, Fatih;Sze, Siu Kwan
通讯作者：
Sze, Siu Kwan