scholarly journals MR‐guided pulsed focused ultrasound improves mesenchymal stromal cell homing to the myocardium

2020 ◽  
Vol 24 (22) ◽  
pp. 13278-13288
Author(s):  
Kee W. Jang ◽  
Tsang‐Wei Tu ◽  
Robert B. Rosenblatt ◽  
Scott R. Burks ◽  
Joseph A. Frank
Keyword(s):  
Mesenchymal Stromal Cell ◽  
Stromal Cell ◽  
Focused Ultrasound ◽  
Cell Homing ◽  
Pulsed Focused Ultrasound

scholarly journals Pulsed Focused Ultrasound Pretreatment Improves Mesenchymal Stromal Cell Efficacy in Preventing and Rescuing Established Acute Kidney Injury in Mice

Stem Cells ◽  
2015 ◽  
Vol 33 (4) ◽  
pp. 1241-1253 ◽  
Author(s):  
Scott R. Burks ◽  
Ben A. Nguyen ◽  
Pamela A. Tebebi ◽  
Saejeong J. Kim ◽  
Michele N. Bresler ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Mesenchymal Stromal Cell ◽  
Stromal Cell ◽  
Focused Ultrasound ◽  
Kidney Injury ◽  
Pulsed Focused Ultrasound ◽  
Ultrasound Pretreatment

scholarly journals Pulsed focused ultrasound enhances the therapeutic effect of mesenchymal stromal cell-derived extracellular vesicles in acute kidney injury

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Mujib Ullah ◽  
Daniel D. Liu ◽  
Sravanthi Rai ◽  
Mehdi Razavi ◽  
Waldo Concepcion ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Therapeutic Effect ◽  
Extracellular Vesicles ◽  
Mesenchymal Stromal Cell ◽  
Stromal Cell ◽  
Molecular Mechanisms ◽  
Focused Ultrasound ◽  
Combined Treatment ◽  
Kidney Injury ◽  
Pulsed Focused Ultrasound

Abstract Background Acute kidney injury (AKI) is characterized by rapid failure of renal function and has no curative therapies. Mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) are known to carry therapeutic factors, which have shown promise in regenerative medicine applications, including AKI. However, there remains an unmet need to optimize their therapeutic effect. One potential avenue of optimization lies in pulsed focused ultrasound (pFUS), where tissues-of-interest are treated with sound waves. pFUS has been shown to enhance MSC therapy via increased cell homing, but its effects on cell-free EV therapy remain largely unexplored. Methods We combine pFUS pretreatment of the kidney with MSC-derived EV therapy in a mouse model of cisplatin-induced AKI. Results EVs significantly improved kidney function, reduced injury markers, mediated increased proliferation, and reduced inflammation and apoptosis. While pFUS did not enhance EV homing to the kidney, the combined treatment resulted in a superior therapeutic effect compared to either treatment alone. We identified several molecular mechanisms underlying this synergistic therapeutic effect, including upregulation of proliferative signaling (MAPK/ERK, PI3K/Akt) and regenerative pathways (eNOS, SIRT3), as well as suppression of inflammation. Conclusion Taken together, pFUS may be a strategy for enhancing the therapeutic efficacy of MSC-derived EV treatment for the treatment of AKI.

scholarly journals Mesenchymal Stromal Cell Homing: Mechanisms and Strategies for Improvement

iScience ◽  
2019 ◽  
Vol 15 ◽  
pp. 421-438 ◽  
Author(s):  
Mujib Ullah ◽  
Daniel D. Liu ◽  
Avnesh S. Thakor
Keyword(s):  
Mesenchymal Stromal Cell ◽  
Stromal Cell ◽  
Cell Homing

scholarly journals HSP70-Mediated NLRP3 Inflammasome Suppression Underlies Reversal of Acute Kidney Injury Following Extracellular Vesicle and Focused Ultrasound Combination Therapy

2020 ◽  
Vol 21 (11) ◽  
pp. 4085
Author(s):  
Mujib Ullah ◽  
Daniel D. Liu ◽  
Sravanthi Rai ◽  
Waldo Concepcion ◽  
Avnesh S. Thakor
Keyword(s):  
Acute Kidney Injury ◽  
Combination Therapy ◽  
Nlrp3 Inflammasome ◽  
Mesenchymal Stromal Cell ◽  
Focused Ultrasound ◽  
Kidney Injury ◽  
Extracellular Vesicle ◽  
Pulsed Focused Ultrasound ◽  
Pro Inflammatory Cytokines

Acute kidney injury (AKI) is the abrupt loss of renal function, for which only supportive therapies exist. Mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) have been shown to be therapeutically effective in treating AKI by spurring endogenous cell proliferation and survival while suppressing inflammation. Pre-treating kidneys with pulsed focused ultrasound (pFUS) has also been shown to enhance MSC therapy for AKI, but its role in MSC-derived EV therapy remains unexplored. Using a mouse model of cisplatin-induced AKI, we show that combination therapy with pFUS and EVs restores physiological and molecular markers of kidney function, more so than either alone. Both pFUS and EVs downregulate heat shock protein 70 (HSP70), the NLRP3 inflammasome, and its downstream pro-inflammatory cytokines IL-1β and IL-18, all of which are highly upregulated in AKI. In vitro knockdown studies suggest that HSP70 is a positive regulator of the NLRP3 inflammasome. Our study therefore demonstrates the ability of pFUS to enhance EV therapy for AKI and provides further mechanistic understanding of their anti-inflammatory and regenerative effects.

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