PMID- 22593018 OWN - NLM STAT- MEDLINE DCOM- 20121129 LR - 20211021 IS - 1549-4918 (Electronic) IS - 1066-5099 (Print) IS - 1066-5099 (Linking) VI - 30 IP - 6 DP - 2012 Jun TI - Enhanced homing permeability and retention of bone marrow stromal cells by noninvasive pulsed focused ultrasound. PG - 1216-27 LID - 10.1002/stem.1099 [doi] AB - Bone marrow stromal cells (BMSCs) 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 number of cells accumulating at sites of pathology. BMSC home to areas of inflammation where local expression of integrins and chemokine gradients is present. We demonstrated that nondestructive 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 BMSCs were intravenously administered 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 eight 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 homing by establishing local chemoattractant gradients and increasing expression of integrins to enhance tropism of cells toward treated tissues. CI - Copyright (c) 2012 AlphaMed Press. FAU - Ziadloo, Ali AU - Ziadloo A AD - Laboratory of Diagnostic Radiology Research, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. FAU - Burks, Scott R AU - Burks SR FAU - Gold, Eric M AU - Gold EM FAU - Lewis, Bobbi K AU - Lewis BK FAU - Chaudhry, Aneeka AU - Chaudhry A FAU - Merino, Maria J AU - Merino MJ FAU - Frenkel, Victor AU - Frenkel V FAU - Frank, Joseph A AU - Frank JA LA - eng GR - ZIA CL040014-03/Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Intramural PL - England TA - Stem Cells JT - Stem cells (Dayton, Ohio) JID - 9304532 RN - 0 (Cytokines) SB - IM MH - Animals MH - Bone Marrow Cells/*cytology/*diagnostic imaging/metabolism MH - Bone Marrow Transplantation/diagnostic imaging/*methods MH - Cell Culture Techniques MH - Cytokines/metabolism MH - Female MH - Humans MH - Immunohistochemistry MH - Kidney/*cytology/*diagnostic imaging MH - Mesenchymal Stem Cells/cytology/diagnostic imaging MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - Stromal Cells/cytology/*transplantation MH - Ultrasonics/*methods MH - Ultrasonography PMC - PMC3356926 MID - NIHMS363906 COIS- Disclosure of Potential Conflicts of Interest The authors indicate no potential conflicts of interest. EDAT- 2012/05/18 06:00 MHDA- 2012/12/10 06:00 PMCR- 2013/06/01 CRDT- 2012/05/18 06:00 PHST- 2012/05/18 06:00 [entrez] PHST- 2012/05/18 06:00 [pubmed] PHST- 2012/12/10 06:00 [medline] PHST- 2013/06/01 00:00 [pmc-release] AID - 10.1002/stem.1099 [doi] PST - ppublish SO - Stem Cells. 2012 Jun;30(6):1216-27. doi: 10.1002/stem.1099.