Wednesday, 16 March 2022 14:08

Lymphoid follicles on-chip replicate human immune function and vaccine responses in vitro Featured

Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University succeeded in culturing human B and T cells in a microfluidic organ chip device and getting them to spontaneously form functional lymphoid follicles. These are normally found in the lymph node and other parts of the human body and mediate immune responses.

The lymphoid follicle chips not only allow researchers to study the normal function of the immune system but can also be used to predict immune responses to different vaccines and to select the best vaccines, as is said in a press release.

Originally, the Wyss scientists wanted to investigate how the behavior of B cells and T cells circulating in the blood changes when they invade a tissue. Therefore, they cultured the cells from human blood samples in a microfluidic organ-on-chip device to mimic the physical conditions. The B cells and T cells were cultured together with an extracellular matrix (ECM) lined in a lower channel of the microfluidic chip. A supply was provided to the cells by the constant flow of a nutrient-containing medium through an upper channel. Due to the flow of culture medium, both cells types organized themselves into 3D structures that resembled "lymphoid follicles".

They observed the secretion of CXCL13, a substance produced in lymph nodes and other parts of the body in response to chronic inflammation. The B cells in the newly formed lymphoid follicles of the chip also secreted AID (activation-induced cytidine deaminase), which is important for activating B cells against specific antigens. Upon stimulation by an antigen, the formation of plasma cells could also be detected.

In a functional study, the researchers added dendritic cells from human donors to the B cells and T cells in the lymphoid follicle chips and "vaccinated" the chips with a vaccine against H5N1. They found that the cells in the chips that received the vaccine as well as an adjuvant produced significantly more plasma cells and anti-influenza antibodies than in these cells grown in 2D cultures or in chips with the vaccine but without an adjuvant.

The Wyss researchers now plan to use their lymphoid follicle chips to work with pharmaceutical companies and the Gates Foundation to test different vaccines and adjuvants.

Original publication:
Goyal, G., Prabhala, P., Mahajan, G., Bausk, B., Gilboa, T., Xie, L., Zhai, Y., Lazarovits, R., Mansour, A., Kim, M. S., Patil, A., Curran, D., Long, J. M., Sharma, S., Junaid, A., Cohen, L., Ferrante, T. C., Levy, O., Prantil-Baun, R., Walt, D. R., Ingber, D. E., Ectopic lymphoid follicle formation and human seasonal influenza vaccination responses recapitulated in an organ-on-a-chip. Adv. Sci. 2022, 2103241.

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