Cyclooxygenase-2 or tumor necrosis factor-α inhibitors attenuate the mechanotransductive effects of pulsed focused ultrasound to suppress mesenchymal stromal cell homing to healthy and dystrophic muscle.
Cyclooxygenase-2 or tumor necrosis factor-α inhibitors attenuate the mechanotransductive effects of pulsed focused ultrasound to suppress mesenchymal stromal cell homing to healthy and dystrophic muscle.
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DOI：
10.1002/stem.1927
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发表时间：
2015-04
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：
Tebebi, Pamela A.;Burks, Scott R.;Kim, Saejeong J.;Williams, Rashida A.;Nguyen, Ben A.;Venkatesh, Priyanka;Frenkel, Victor;Frank, Joseph A.
关键词：
Maximal homing of infused stem cells to diseased tissue is critical for regenerative medicine. Pulsed focused ultrasound (pFUS) is a clinically relevant platform to direct stem cell migration. Through mechanotransduction, pFUS establishes local gradients of cytokines, chemokines, trophic factors (CCTF) and cell adhesion molecules (CAM) in treated skeletal muscle that subsequently infused mesenchymal stromal cells (MSC) can capitalize to migrate into the parenchyma. Characterizing molecular responses to mechanical pFUS effects revealed tumor necrosis factor-alpha (TNFα) drives cyclooxygenase-2 (COX2) signaling to locally increase CCTF/CAM that are necessary for MSC homing. pFUS failed to increase chemoattractants and induce MSC homing to treated muscle in mice pretreated with ibuprofen (non-specific COX inhibitor) or etanercept (TNFα inhibitor). pFUS-induced MSC homing was also suppressed in COX2-knockout mice, demonstrating ibuprofen blocked the mechanically-induced CCTF/CAM by acting on COX2. Anti-inflammatory drugs, including ibuprofen, are administered to muscular dystrophy (MD) patients and ibuprofen also suppressed pFUS-induced homing to muscle in a mouse model of MD. Drug interactions with cell therapies remain unexplored and are not controlled for during clinical cell therapy trials. This study highlights potentially negative drug-host interactions that suppress stem cell homing and could undermine cell-based approaches for regenerative medicine.
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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：
20.3
作者：
Gavina, Manuela;Belicchi, Marzia;Torrente, Yvan
通讯作者：
Torrente, Yvan
影响因子：
4
作者：
Kim, Saejeong;Chaudhry, Aneeka;Frank, Joseph A.
通讯作者：
Frank, Joseph A.
影响因子：
4.4
作者：
Chandel, NS;Trzyna, WC;Schumacker, PT
通讯作者：
Schumacker, PT
影响因子：
17.1
作者：
Fischbach MA;Bluestone JA;Lim WA
通讯作者：
Lim WA