Urinary bladder smooth muscle regeneration utilizing bone marrow derived mesenchymal stem cell seeded elastomeric poly(1,8-octanediol-co-citrate) based thin films.
Bladder regeneration studies have yielded inconclusive results possibly due to the use of unfavorable cells and primitive scaffold design. We hypothesized that human mesenchymal stem cells seeded onto poly(1,8-octanediol-co-citrate) elastomeric thin films would provide a suitable milieu for partial bladder regeneration. POCfs were created by reacting citric acid with 1,8-octanediol and seeded on opposing faces with human MSCs and urothelial cells; normal bladder smooth muscle cells and UCs, or unseeded POCfs. Partial cystectomized nude rats were augmented with the aforementioned POCfs, enveloped with omentum and sacrificed at 4 and 10 weeks. Isolated bladders were subjected to Trichrome and anti-human gamma-tubulin, calponin, caldesmon, smooth muscle gamma-actin, and elastin stainings. Mechanical testing of POCfs revealed a Young's modulus of 138 kPa with elongation 137% its initial length without permanent deformation demonstrating its high uniaxial elastic potential. Trichrome and immunofluorescent staining of MSC/UC POCf augmented bladders exhibited typical bladder architecture with muscle bundle formation and the expression and retention of bladder smooth muscle contractile proteins of human derivation. Quantitative morphometry of MSC/UC samples revealed muscle/collagen ratios approximately 1.75x greater than SMC/UC controls at 10 weeks. Data demonstrate MSC seeded POCfs support partial regeneration of bladder tissue in vivo.
Sharma
Arun K
AK
Children's Memorial Hospital Chicago, Division of Pediatric Urology, 2300 Children's Plaza, Chicago, IL 60614, USA. arun-sharma@northwestern.edu
Hota
Partha V
PV
Matoka
Derek J
DJ
Fuller
Natalie J
NJ
Jandali
Danny
D
Thaker
Hatim
H
Ameer
Guillermo A
GA
Cheng
Earl Y
EY
D000818:Animals; D001391:Azo Compounds; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002951:Citrates / Q000494:pharmacology*; D019343:Citric Acid / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism; D055119:Elastic Modulus / Q000187:drug effects; D020724:Elastomers / Q000494:pharmacology*; D004801:Eosine Yellowish-(YS); D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D008739:Methyl Green; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011108:Polymers / Q000494:pharmacology*; D051381:Rats; D011923:Rats, Nude; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D013194:Staining and Labeling; D054457:Tissue Scaffolds / Q000737:chemistry; D001743:Urinary Bladder / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D001391:Azo Compounds; D002951:Citrates; D020724:Elastomers; D011108:Polymers; C513817:poly(1,8-octanediol citrate); C017768:trichrome stain; D019343:Citric Acid; D008739:Methyl Green; D003094:Collagen; D004801:Eosine Yellowish-(YS)