Unmet NeedThe critically important goal of regenerative medicine is the stimulation of
in vivo wound healing and the production of functional tissue to repair or replace tissues loss to injury or disease. Extracellular matrix (ECM) materials are acellular tissue derived scaffolds commonly used in tissue regeneration following malignant or benign tumor resections, as ECM promotes pro-regenerative processes such as cell proliferation, angiogenesis, stem-cell recruitment, and type 2 immune responses. While these processes are favorable for tissue repair, they are also critical for the formation of solid tumors. Presently, it is unknown if these regenerative, ECM-based strategies for tissue repair also provide a fertile environment for
de novo or recurrent tumor formation. This could be problematic if ECM material is used to for clinical reconstruction following resection of cancerous tumors. Consequently, there is a need to determine the effects of ECM material on the establishment of a pro-tumor microenvironment
in vivo.
Technology OverviewJohns Hopkins researchers determined that pro-regenerative urinary bladder ECM material (UBM) inhibited the formation of tumors in a B16-F10 melanoma mouse model in an immune-dependent manner. The UBM particle scaffold led to a biased Th2-M2 type 2, anti-inflammatory immune profile and also increased recruitment of both myeloid and lymphoid cells. This type-2 skewed immune phenotype and tumor inhibition was ablated upon implementation of the UBM scaffold in lymphocyte deficient mice (Rag1-/-). Tumor inhibition and the UBM material response was rescued by the repopulation of CD4+ T-cells.
Stage of DevelopmentThe inventors demonstrated that decellularized ECM materials used in regenerative applications do not appear to promote melanoma tumor formation
in vivo. Future studies will be conducted to determine if this tumor inhibition occurs in humans for a wide variety of cancers and ECM materials and if synergizing this ECM-derived immune environment with immunotherapeutics will enhance killing of tumors and metastases in patients.
