Bone marrow derived cells facilitate urinary bladder regeneration by attenuating tissue inflammatory responses.
BACKGROUND
Inflammatory responses following tissue injury are essential for proper tissue regeneration. However, dysfunctional or repetitive inflammatory tissue assaults can lead to poor tissue regeneration and ultimate tissue failure via fibrosis. Previous attempts at urinary bladder tissue regeneration utilizing polymeric and biologic scaffolding materials tended to elicit these responses leading to poor tissue regeneration. Recent advances in bladder regeneration utilizing bone marrow derived mesenchymal stem cells (MSCs) and CD34(+) hematopoietic stem/progenitor cells (HSPCs) with biocompatible citric acid based scaffolds have provided an environment that not only promotes the growth of architecturally germane and physiologically functional tissue, but also modulates aspects of the innate immune response.


METHODS
Within this study MSCs, CD34(+) HSPCs, or MSC/CD34(+) HSPC seeded POC [poly (1,8-octanediol-co-citrate)] scaffolds were utilized in an established rodent bladder augmentation model to evaluate inflammation as it pertains to bladder tissue regeneration.


RESULTS
Quantified data from post-augmentation regenerated tissue samples at the 4 week time-point demonstrated that POC/MSC and POC/MSC + CD34(+) HSPC grafts markedly reduced the presence of pro-inflammatory CD68(+) macrophages and MPO(+) neutrophils compared to unseeded POC or POC/CD34(+) HSPC-only seeded grafts. Pro-inflammatory cytokines TNFα and IL-1b were also significantly down-regulated with a concomitant increase in the anti-inflammatory cytokines IL-10 and IL-13 in the aforementioned POC/MSC and POC/MSC + CD34(+) HSPC composites. Furthermore, this led to fewer instances of bladder tissue granuloma formation combined with greater muscle content and tissue angiogenic events as previous data has demonstrated.


CONCLUSIONS
Data indicates that POC/MSC and POC/MSC + CD34(+) HSPC grafts attenuate the innate inflammatory response and promote bladder tissue regeneration.
Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Pediatric Urology, Chicago, IL, USA.
Matthew I
MI
Bury
Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Pediatric Urology, Chicago, IL, USA.
Natalie J
NJ
Fuller
Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Pediatric Urology, Chicago, IL, USA.
Linnea
L
Wethekam
Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Pediatric Urology, Chicago, IL, USA ; Northwestern University Feinberg School of Medicine, Department of Urology, Chicago, IL, USA ; Northwestern University, Simpson Querrey Institute for BioNanotechnology, Chicago, IL, USA ; Northwestern University, Department of Biomedical Engineering, Evanston, IL, USA.
Arun K
AK
Sharma
CD34+ hematopoietic progenitors; bone marrow; hematopoietic stem cells; mesenchymal stem cells; tissue regeneration