Decellularized Whole-Organ Pre-vascularization: A Novel Approach for Organogenesis.

Area of Science:

• Regenerative Medicine
• Biomaterials Engineering
• Transplantation Biology

Background:

• Whole-organ decellularization is a promising technique for tissue engineering but faces challenges with vascularization and graft survival post-implantation.
• Intra-vascular blood coagulation in re-cellularized scaffolds limits long-term graft survival.
• Axial pre-vascularization offers an alternative strategy for enhancing scaffold vascularity.

Purpose of the Study:

• To investigate the potential of an axially pre-vascularized whole-organ scaffold for pancreatic islet transplantation.
• To evaluate the efficacy of using bone marrow (BM) or adipose-derived stem cells (ADSCs) to enhance scaffold vascularization and islet engraftment.
• To assess the functional recovery of diabetic rats following transplantation into engineered scaffolds.

Main Methods:

• Whole rat livers were decellularized and implanted with an arteriovenous bundle.
• Scaffolds were injected with BM, ADSCs, or HBSS, followed by islet equivalent (IEQ) transplantation after 5 weeks.
• Diabetic recipient rats were monitored for blood glucose, body weight, and underwent glucose tolerance tests and immunohistochemical analyses.

Main Results:

• Scaffolds seeded with BM and ADSCs showed improved blood glucose normalization and partial correction in diabetic rats compared to acellular controls.
• Micro-CT imaging confirmed vascular sprouting within the scaffold.
• Immunohistochemistry revealed insulin-positive cells and increased von-Willebrand factor expression in seeded scaffolds, indicating vascularization and islet presence.

Conclusions:

• Axially pre-vascularized whole-organ scaffolds represent a viable approach for islet transplantation.
• Scaffolds seeded with BM or ADSCs demonstrated superior performance over acellular scaffolds.
• This strategy holds significant potential for improving outcomes in organ engineering and transplantation.