Decellularized Wharton's Jelly extracellular matrix (DWJM) as biological scaffold supporting cells from degenerated intervertebral disc.

Regenerative therapies for intervertebral disc (IVD) injuries are currently a major worldwide challenge. Decellularized extracellular matrices (ECM) from many tissues have been proposed as biomaterials with good regenerative capacity and promising therapeutic potential. In this context, human perinatal tissues have been recently evaluated as abundant, cost effective and successful source of ECM components. In recent years we focused on the potential of decellularized Wharton’s jelly matrix (DWJM) from human umbilical cord as scaffold and and trophic factors source for degenerate IVD cells. We use an efficient detergent-enzymatic treatment to produce DWJM maintaining its native microarchitecture and protein content. We found that DWJM produces sizeable 3D cell aggregates when combined with IVD cells, significantly improving the degenerated phenotype of the cells. In this condition the cells remain viable, increase the expression of critical regulators of IVD homeostasis, such as SOX2, SOX9, TRPS1 and FOXO3a transcription factors, and actively respond to hypoxic priming (2% pO2, for 48 hours). This suggests the ability of DWJM to provide appropriate stimuli to dampen the degenerated IVD cell phenotype and to promote anabolic activity in cells which are constitutively characterized by poor reparative capacity. Thanks to this evidence and in order to develop an innovative DWJM based IVD tissue engineering approach, we are now moving towards: - the production of cross-linked composite scaffolds, combining DWJM with alginate and gelatin, taking into consideration different shapes, polymers ratios and porosity. To date we verified that many of the DWJM-based scaffolds produced so far retain the ability to support IVD cells behavior and maintain an anabolic potential over time, with no evident toxicity - the optimization of DWJM properties, combining it with bioactive molecules from specific plant extracts to produce “herbal scaffolds”.