Impact of bladder-derived acellular matrix, growth factors, and extracellular matrix constituents on the survival and multipotency of marrow-derived mesenchymal stem cells

J Biomed Mater Res A. 2012 Jan;100(1):72-83. doi: 10.1002/jbm.a.33230. Epub 2011 Oct 4.

Abstract

We investigate the effect of bladder-derived acellular matrix (ACM) on bone marrow mesenchymal stem cells (BM-MSC) growth, survival, and differentiation, and evaluate the effect of collagen I and IV on BM-MSC differentiation potential to SMC. BM-MSCs isolated from CD1(_) mice were characterized by surface markers and differentiation into different lineages. BM-MSC SMC potential was further evaluated in stem cell medium alone or supplemented with TGF-β1 and recombinant human platelet-derived growth factor (PDGF-BB) on plastic, collagen I and IV using western blot. Furthermore, BM-MSCs were seeded on porcine derived ACM-fortified with hyaluronic acid and cultured in Mesencult+-growth factors, bone, or fat induction media for 3 weeks. Seeded constructs were evaluated by H&E, Ki67 assay, Oil red O, and Alizarin red stain. SMC differentiation was semiquantified via immunohistochemistry. BM-MSCs differentiated into fat and bone when induced. In Mesencult, BM-MSCs differentiated into SMC, expressing α-SMA, calponin, and MHC. BM-MSCs cultured on collagen I and IV reduced expression of SMC and MHC compared to plastic. On ACM-HA, BM-MSCs maintained multipotent state by differentiating to bone and fat when induced. In Mesencult, BM-MSC-seeded ACM-HA expressed α-SMA, calponin, and MHC. TGF-β1 and PDGF-BB enhanced SMC differentiation on collagens and ACM-HA. SMC proteins expression by BM-MSC varies depending on culture substrate. SMC markers are expressed higher on plastic and lower on collagen I, IV, and ACM-HA, suggesting these substrates preferentially maintain undifferentiated state of BM-MSC, which could be advantageous for incorporation of cell-seeded grafts to permit host modulation of tissue regeneration.

MeSH terms

  • Actins / metabolism
  • Animals
  • Becaplermin
  • Biomarkers / metabolism
  • Bone Marrow Cells / cytology*
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Calcium-Binding Proteins / metabolism
  • Calponins
  • Cell Differentiation / drug effects
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Collagen Type I / pharmacology
  • Collagen Type IV / pharmacology
  • Culture Media / pharmacology
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism*
  • Humans
  • Hyaluronic Acid / pharmacology
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Microfilament Proteins / metabolism
  • Multipotent Stem Cells / cytology*
  • Multipotent Stem Cells / drug effects
  • Multipotent Stem Cells / metabolism
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism
  • Myosin Heavy Chains / metabolism
  • Phenotype
  • Plastics
  • Proto-Oncogene Proteins c-sis / pharmacology*
  • Sus scrofa
  • Transforming Growth Factor beta1 / pharmacology*
  • Urinary Bladder / metabolism*

Substances

  • Actins
  • Biomarkers
  • Calcium-Binding Proteins
  • Collagen Type I
  • Collagen Type IV
  • Culture Media
  • Microfilament Proteins
  • Plastics
  • Proto-Oncogene Proteins c-sis
  • Transforming Growth Factor beta1
  • Becaplermin
  • Hyaluronic Acid
  • Myosin Heavy Chains