Bone marrow derived cells facilitate urinary bladder regeneration by attenuating tissue inflammatory responses

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Immunology

Background:

• Inflammatory responses are crucial for tissue repair but can impede bladder regeneration if dysregulated.
• Previous bladder regeneration attempts using scaffolds often triggered adverse inflammatory reactions, leading to fibrosis and tissue failure.
• Recent strategies leverage biocompatible scaffolds with stem cells to modulate immune responses and improve tissue regeneration.

Purpose of the Study:

• To evaluate the impact of mesenchymal stem cells (MSCs) and CD34(+) hematopoietic stem/progenitor cells (HSPCs) on inflammation during bladder tissue regeneration.
• To assess the efficacy of poly (1,8-octanediol-co-citrate) (POC) scaffolds seeded with MSCs and/or HSPCs in a rodent bladder augmentation model.

Main Methods:

• Utilized a rodent bladder augmentation model with POC scaffolds seeded with MSCs, CD34(+) HSPCs, or a combination of both.
• Quantified inflammatory markers, including CD68(+) macrophages and MPO(+) neutrophils, in regenerated tissue samples at 4 weeks post-augmentation.
• Measured pro-inflammatory (TNFα, IL-1b) and anti-inflammatory (IL-10, IL-13) cytokine levels.

Main Results:

• POC scaffolds seeded with MSCs and/or CD34(+) HSPCs significantly reduced pro-inflammatory macrophages and neutrophils compared to unseeded or HSPC-only seeded scaffolds.
• Down-regulation of TNFα and IL-1b, with a concurrent increase in IL-10 and IL-13, was observed in POC/MSC and POC/MSC + CD34(+) HSPC grafts.
• These immunomodulatory effects correlated with reduced granuloma formation, increased muscle content, and enhanced angiogenesis in regenerated bladder tissue.

Conclusions:

• POC scaffolds combined with MSCs and CD34(+) HSPCs effectively attenuate the innate inflammatory response in bladder tissue regeneration.
• This approach promotes enhanced bladder tissue regeneration, characterized by improved tissue architecture and vascularization.
• The findings suggest a potential therapeutic strategy for improving outcomes in bladder augmentation and repair.