Decellularized Lymph Node Scaffolding as a Carrier for Dendritic Cells to Induce Anti-Tumor Immunity

Abstract

In recent decades, the decellularized extracellular matrix (ECM) has shown potential as a promising scaffold for tissue regeneration. In this study, an organic acid decellularized lymph node (dLN) was developed as a carrier for dendritic cells (DCs) to induce antitumor immunity. The dLNs were prepared by formic acid, acetic acid, or citric acid treatment. The results showed highly efficient removal of cell debris from the lymph node and great preservation of ECM architecture and biomolecules. In addition, bone marrow dendritic cells (BMDCs) grown preferably inside the dLN displayed the maturation markers CD80, CD86, and major histocompatibility complex (MHC)-II, and they produced high levels of interleukin (IL)-1β, IL-6, and IL-12 cytokines when stimulated with ovalbumin (OVA) and CpG oligodeoxynucleotides (CPG-ODN). In an animal model, the BMDC-dLN completely rejected the E.G7-OVA tumor. Furthermore, the splenocytes from BMDC-dLN-immunized mice produced more interferon gamma, IL-4, IL-6, and IL-2, and they had a higher proliferation rate than other groups when re-stimulated with OVA. Hence, BMDC-dLN could be a promising DC-based scaffold for in vivo delivery to induce potent antitumor immunity.

Plug-and-Play Lymph Node-on-Chip: Secondary Tumor Modeling by the Combination of Cell Spheroid, Collagen Sponge and T-Cells

“…In general, the size of the pores in a normal lymph node can range from 20–50 μm in diameter. These pores allow lymph fluids to flow through the lymph node, where they can be filtered and analyzed by immune cells [ 41 ].…”

Decellularization of tumours: A new frontier in tissue engineering

“…-The osmotic shock kills the cells, but it does not remove the cell waste that it releases to the matrix. Physical 3,12,75,76,[79][80][81][82][83][84][85][86][87][88] -CO 2 does not remain within the tissue and therefore, extensive washing is not required. -CO 2 is non-polar, so a polar entrainer is necessary to remove the polar phospholipid membrane.…”

“… 78 The study by Pinto et al evidences that some physical methods like agitation, rotation, shaking or sonication can facilitate the decellularization process. 83 – 86 Freeze-thaw is another physical method that has been used in the decellularization of tumours. The work by Romero-López and colleagues 87 is an example, where an initial freeze-thaw cycle was included in the decellularization protocol, followed by surfactant treatment and extensive washing to eliminate the detergents.…”

Decellularised scaffolds: just a framework? Current knowledge and future directions

“…Other acids that have been used as decellularisation agents are formic acid, acetic acid and citric acid. For example, Lin et al 34 used these three acids in the decellularisation of inguinal and popliteal lymph nodes harvested from Lewis rats.…”