Enhanced homing permeability and retention of bone marrow stromal cells by noninvasive pulsed focused ultrasound.
Enhanced homing permeability and retention of bone marrow stromal cells by noninvasive pulsed focused ultrasound.
复制标题
DOI：
10.1002/stem.1099
复制
发表时间：
2012-06
期刊：
影响因子：
5.2
通讯作者：
Frank, Joseph A.
中科院分区：
文献类型：
--
作者：
Ziadloo, Ali;Burks, Scott R.;Gold, Eric M.;Lewis, Bobbi K.;Chaudhry, Aneeka;Merino, Maria J.;Frenkel, Victor;Frank, Joseph A.
关键词：
骨髓基质细胞（BMSC）在疾病治疗中显示出巨大的希望，但其治疗效果往往受到系统给药细胞归巢效率低的限制，这导致病理部位的细胞数量较少。BMSC是炎症区域的家，在那里局部表达整合素和趋化因子梯度存在。我们证明，非破坏性脉冲聚焦超声（pFUS）暴露强调超声与组织相互作用的机械效应，可诱导小鼠肾脏中化学引诱剂（即细胞因子、整合素和生长因子）的局部和短暂升高。ppfus诱导的细胞因子上调发生在治疗后约1天，并在第3天恢复到对侧肾脏水平。这个细胞因子表达显著增加的窗口伴随着其他营养因子和整合素的局部增加，这些因子和整合素已被证明可以促进BMSC归巢。当pFUS治疗后单肾静脉给予BMSC时，与对侧肾脏相比，在治疗肾脏中观察到BMSC的归家、通透性和潴留增强。组织学分析显示，在治疗后第1天和第3天，治疗后肾脏小管周围区域的BMSC增加了8倍。此外，在给予BMSC后，ppfus处理肾脏的细胞因子水平与对照组相似，表明BMSC调节了细胞因子水平。pFUS可以通过建立局部趋化剂梯度和增加整合素的表达来增强BMSC对治疗组织的趋向性，从而潜在地改善基于细胞的治疗方法，作为一种无创的方式来靶向BMSC归巢。
Bone marrow stromal cells (BMSC) have shown significant promise in the treatment of disease, but their therapeutic efficacy is often limited by inefficient homing of systemically-administered cells, which results in low numbers of cells accumulating at sites of pathology. BMSC home to areas of inflammation where local expression of integrins and chemokine gradients are present. We demonstrated that non-destructive pulsed focused ultrasound (pFUS) exposures that emphasize the mechanical effects of ultrasound-tissue interactions induced local and transient elevations of chemoattractants (i.e., cytokines, integrins, and growth factors) in the murine kidney. pFUS-induced upregulation of cytokines occurred through approximately 1 day post-treatment and returned to contralateral kidney levels by day 3. This window of significant increases in cytokine expression was accompanied by local increases of other trophic factors and integrins that have been shown to promote BMSC homing. When BMSC were administered intravenously following pFUS treatment to a single kidney, enhanced homing, permeability, and retention of BMSC was observed in the treated kidney versus the contralateral kidney. Histological analysis revealed up to 8 times more BMSC in the peritubular regions of the treated kidneys on days 1 and 3 post-treatment. Furthermore, cytokine levels in pFUS-treated kidneys following BMSC administration were found to be similar to controls, suggesting modulation of cytokine levels by BMSC. pFUS could potentially improve cell-based therapies as a noninvasive modality to target BMSC homing by establishing local chemoattractant gradients and increasing expression of integrins to enhance tropism of BMSC toward treated tissues.
登录
查看更多内容
影响因子：
2.9
作者：
Hancock, Hilary A.;Smith, Lauren H.;Cuesta, Julian;Durrani, Amir K.;Angstadt, Mary;Palmeri, Mark L.;Kimmel, Eitan;Frenkel, Victor
通讯作者：
Frenkel, Victor
影响因子：
11.3
作者：
Kyrtatos, Panagiotis G.;Lehtolainen, Pauliina;Lythgoe, Mark F.
通讯作者：
Lythgoe, Mark F.
影响因子：
6.7
作者：
Lee, P. H.;Kim, J. W.;Huh, K.
通讯作者：
Huh, K.
影响因子：
3.3
作者：
Kondziolka, D;Steinberg, GK;McGrogan, M
通讯作者：
McGrogan, M
影响因子：
4.6
作者：
Hwang, Joo Ha;Zhou, Yufeng;Crum, Lawrence A.
通讯作者：
Crum, Lawrence A.