Introduction

The outcome of tissue engineered organ transplants depends on the capacity of the biomaterial to promote a pro-healing response once implanted in vivo. Multiple studies, including ours, have demonstrated the possibility of using the extracellular matrix (ECM) of animal organs as a platform for tissue engineering and more recently, discarded human organs have also been proposed as a scaffold source. It is known that natural matrices present diverse immune properties when compared to artificial biomaterials. However, how these properties compare between diseased and healthy ECM and artificial scaffolds has not yet been defined.

Methods

We used decellularized renal ECM derived from WT mice and from mice affected by Alport Syndrome as a model of renal failure with extensive fibrosis, at different time-points of disease progression. We characterized the morphology and composition of these ECMs and compared their in vitro effects on macrophage activation with that of synthetic scaffolds commonly used in the clinic (collagen type I and poly-L-(lactic) acid, PLLA).

Results

We showed that ECM derived from Alport kidneys differed in fibrous protein deposition (col I, col IV?1,2 and fibronectin) and cytokine content (Resistin, TIM-1/ KIM-1, DPPIV/CD26 and Reg3G) when compared to ECM derived from WT kidneys. Yet, both WT and Alport renal ECM induced macrophage differentiation mainly towards a reparative (M2) phenotype (reduced CD80), while artificial biomaterials towards an inflammatory (M1) phenotype. Anti-inflammatory properties of natural ECMs were lost when homogenized, hence three-dimensional structure of ECM seems crucial for generating an anti-inflammatory response.

Conclusions

Together, these data support the notion that natural ECM, even if derived from diseased kidneys promote a M2 protolerogenic macrophage polarization, thus providing novel insights on the applicability of ECM obtained from discarded organs as ideal scaffold for tissue engineering.

Funding

GOFARR Laboratory