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Targeted homing of mesenchymal stem cells (MSC) by noninvasive pulsed-focused-ultrasound improves the protective and regenerative capabilities of MSC during cisplatinum-induced acute tubular necrosis in mice

Thursday, November 07, 2013 — Poster Session II

12:00 p.m. – 2:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • S.R. Burks
  • B.A. Nguyen
  • P.A. Tebebi
  • A. Ziadloo
  • S.J. Kim
  • V. Frenkel
  • J.A. Frank


IV-injected mesenchymal stem cells (MSC) therapies are promising, but require cell homing to diseased loci. Homing is inefficient, difficult to target, and requires pathological inflammatory homing cues. Nondestructive pulsed focused ultrasound (pFUS) can be precisely targeted where its mechanical effects invigorate local molecular responses (upregulated chemoattractants) that increase homing of IV MSC in healthy tissue. We examined pFUS-targeting of MSC in cisplatinum-induced acute tubular necrosis (ATN), a condition with dynamic inflammatory profiles, and therapeutic benefit of targeting additional MSC. pFUS increased chemoattractant expression in kidneys 1 day post-cisplatinum (no inflammation/renal failure) or 4 days post-cisplatinum (high inflammation/renal failure). pFUS-targeted MSC 1 day post-cisplatinum improved renal function and morphology by 4 days post-cisplatinum compared to untargeted MSC. Most MSC-based therapies for ATN administer cells soon after post-cisplatinum (≤1 day) and MSC regeneration of already-damaged kidneys (at ≥3 days post-cisplatinum) is unknown. When pFUS/MSC treatment is delayed until 3 days post-cisplatinum, untargeted MSC significantly improve survival at 6 days post-cisplatinum, but targeting MSC by pFUS further improves survival and significantly improves renal function within 24hr post-treatment. pFUS can be rapidly implemented clinically, allow spatiotemporal control over homing (including outside acute inflammatory periods), and improve therapeutic efficacy.

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