Decellularized Lymph Node Scaffolding as a Carrier for Dendritic Cells to Induce Anti-Tumor Immunity.
Hung-Jun LinWeu WangYi-You HuangWei-Tsen LiaoTing-Yu LinShyr-Yi LinDer-Zen LiuPublished in: Pharmaceutics (2019)
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.
Keyphrases
- dendritic cells
- extracellular matrix
- lymph node
- highly efficient
- bone marrow
- immune response
- regulatory t cells
- tissue engineering
- stem cells
- neoadjuvant chemotherapy
- sentinel lymph node
- gene expression
- signaling pathway
- mesenchymal stem cells
- squamous cell carcinoma
- radiation therapy
- type diabetes
- cell therapy
- climate change
- rectal cancer
- metabolic syndrome
- early stage
- insulin resistance
- combination therapy
- human health