Graduate School of BASE, Tokyo University of Agriculture and Technology, Koganei, Tokyo, 184-8588, Japan.
National Center for Child Health and Development, Setagaya, Tokyo, 157-8535, Japan.
J Med Ultrason (2001). 2023 Apr;50(2):121-129. doi: 10.1007/s10396-022-01277-5. Epub 2023 Jan 12.
Although cellular immunotherapy is expected as a new cancer treatment, its therapeutic efficiency is limited in solid tumors, because most cells return to the bloodstream rather than adhere to the target site. Therefore, we are motivated to develop a technique to concentrate the cells in the blood flow using active control of bubble-surrounded cells under ultrasound exposure considering both aspects of cell controllability and viability.
We prepared a lipid bubble conjugating ligand to adhere to the surface of the T-cells. First, we evaluated the cell controllability by retaining the cells on a wall of an artificial blood vessel through continuous ultrasound exposure. Next, we investigated the cell viability under ultrasound exposure in a suspension with various bubble concentrations.
We estimated the concentration of bubbles when the adhesion to the cell surface was saturated. Then, we evaluated the cell viability with various conditions of ultrasound exposure and bubble concentrations. However, it was confirmed that cell damage occurred under conditions that achieved proper control of the cells. Therefore, we exposed the cells to burst waves to reduce the applied ultrasound intensity. Consequently, the significant increase in cell viability was confirmed to be inversely proportional to the duty ratio.
To retain cells on a vessel wall, determining the appropriate ultrasound condition including sound pressure and waveform is important to maintain cell viability.
虽然细胞免疫疗法有望成为一种新的癌症治疗方法，但它在实体肿瘤中的治疗效果有限，因为大多数细胞会回到血液中，而不是黏附在靶位上。因此，我们致力于开发一种技术，通过在超声暴露下主动控制被气泡包围的细胞，在考虑细胞可控性和活力的两方面因素的情况下，将血液中的细胞集中起来。
我们制备了一种脂质泡结合配体，使其能够黏附在 T 细胞的表面。首先，我们通过持续的超声暴露来评估细胞的可控性，从而将细胞保留在人工血管的壁上。接下来，我们在不同气泡浓度的悬浮液中研究了超声暴露下的细胞活力。
我们估计了当细胞表面黏附达到饱和时气泡的浓度。然后，我们根据不同的超声暴露条件和气泡浓度来评估细胞活力。然而，我们确认在实现细胞适当控制的条件下会发生细胞损伤。因此，我们使用爆裂波来暴露细胞，以降低应用的超声强度。结果，细胞活力的显著增加被证实与占空比成反比。
为了将细胞保留在血管壁上，确定包括声压和波形在内的适当超声条件对于维持细胞活力很重要。
