Attenuation of early airway obstruction by mesenchymal stem cells in a murine model of heterotopic tracheal transplantation.
Attenuation of early airway obstruction by mesenchymal stem cells in a murine model of heterotopic tracheal transplantation.
复制标题
DOI：
10.1016/j.healun.2010.09.012
复制
发表时间：
2011-03
期刊：
影响因子：
--
通讯作者：
Rojas M
中科院分区：
文献类型：
--
作者：
Grove DA;Xu J;Joodi R;Torres-Gonzales E;Neujahr D;Mora AL;Rojas M
肺移植的长期成功受到闭塞性细支气管炎（OB）的限制。到目前为止，对OB发病机制的全面了解还难以捉摸。骨髓来源的间充质干细胞（MSC）已被证明可以调节多种疾病模型中受损肺的修复。我们假设在异位气管移植模型中，注射MSC可以预防早期气道阻塞（AO）的发生。44例BALB/c和C57BL/6供体气管移植至22例C57BL/6受体。移植时，向13只同种异体受体小鼠注射5 × 105个不同来源的MSCs。为了证实免疫反应在AO生成中的作用，我们对11例Balb/c气管移植后的受者使用了一种可渗透的NF-κB抑制剂。移植后，给予MSC可抑制98%的胶原腔内阻塞，TGF-β表达降低到与等移植对照组相似的水平。这些作用与抗炎细胞因子IL-10的表达显著升高（p<0.05）相关。NF-κB抑制剂在第7天和第14天组中TGF-β的表达降低，导致气道阻塞减少60%，气道炎症细胞减少。我们的观察结果表明，在小鼠模型中，MSC可能通过调节免疫反应改变TGF-β的表达来阻止气道闭塞的发展。
Long-term success in lung transplantation is limited by obliterative bronchiolitis (OB). As of this time complete understanding of the mechanisms of OB has been elusive. Bone marrow-derived mesenchymal stem cells (MSC) have been shown to modulate repair of the injured lung in multiple disease models. We hypothesized that the injection of MSC would prevent the development of early airway obstruction (AO) in the heterotopic tracheal transplant model. 44 tracheas from BALB/c and C57BL/6 donors were transplanted into 22 C57BL/6 recipients. At the time of transplant 13 of the allogeneic recipient mice were injected with 5 × 105 MSCs from various murine sources. To confirm the role of the immune response in the generation of AO we used a permeable inhibitor of NF-κB in 11 recipients after been transplanted with 22 Balb/c tracheas After transplant, administration of MSC inhibited intraluminal obstruction by collagen in a 98% and TGF-β expression reduced to similar levels that the ones observed in the isograft controls. These effects were associated with a significant (p<0.05), increase in the expression of the anti-inflammatory cytokine IL-10. NF-κB inhibitor shows a decrease in the expression of TGF-β in the day 7 and day 14 groups resulting in a 60% reduction of luminal obstruction as well as the reduction of inflammatory cells to the airway. Our observations suggest that the administration of MSC prevents the development of airway occlusion in a mouse model likely via modulation immune response altering TGF-β expression.
登录
查看更多内容
影响因子：
46.9
作者：
Rojas, M;Donahue, JP;Lin, YZ
通讯作者：
Lin, YZ
影响因子：
4.4
作者：
Gupta, Naveen;Su, Xiao;Matthay, Michael A.
通讯作者：
Matthay, Michael A.
影响因子：
2.6
作者：
Theise, ND;Henegariu, O;Krause, DS
通讯作者：
Krause, DS
DOI：
10.1152/ajplung.00431.2006
发表时间：
2007-07-01
影响因子：
4.9
作者：
Xu, Jianguo;Woods, Charles R.;Rojas, Mauricio
通讯作者：
Rojas, Mauricio
DOI：
10.1073/pnas.1432929100
发表时间：
2003-07-08
影响因子：
11.1
作者：
Ortiz, LA;Gambelli, F;Phinney, DG
通讯作者：
Phinney, DG