Hybrid Complexes of High and Low Molecular Weight Hyaluronans Highly Enhance HASCs Differentiation: Implication for Facial Bioremodelling

Cell Physiol Biochem. 2017;44(3):1078-1092. doi: 10.1159/000485414. Epub 2017 Nov 27.


Background/aims: Adipose-derived Stem Cells (ASCs) are used in Regenerative Medicine, including fat grafting, recovery from local tissue ischemia and scar remodeling. The aim of this study was to evaluate hyaluronan based gel effects on ASCs differentiation and proliferation.

Methods: Comparative analyses using high (H) and low (L) molecular weight hyaluronans (HA), hyaluronan hybrid cooperative complexes (HCCs), and high and medium cross-linked hyaluronan based dermal fillers were performed. Human ASCs were characterized by flow cytometry using CD90, CD34, CD105, CD29, CD31, CD45 and CD14 markers. Then, cells were treated for 7, 14 and 21 days with hyaluronans. Adipogenic differentiation was evaluated using Oil red-O staining and expression of leptin, PPAR-γ, LPL and adiponectin using qRT-PCR. Adiponectin was analyzed by immunofluorescence, PPAR-γ and adiponectin were analyzed using western blotting. ELISA assays for adiponectin and leptin were performed.

Results: HCCs highly affected ASCs differentiation by up-regulating adipogenic genes and related proteins, that were also secreted in the culture medium. H-HA and L-HA induced a lower level of ASCs differentiation.

Conclusion: HCCs-based formulations clearly enhance adipogenic differentiation and proliferation, when compared with linear HA and cross-linked hyaluronans. Injection of HCCs in subdermal fat compartment may recruit and differentiate stem cells in adipocytes, and considerably improving fat tissue renewal.

Keywords: Adipogenic differentiation; Adipose stem cells; Antiaging medical devices; Hyaluronic acid formulations.

MeSH terms

  • Adipogenesis / drug effects
  • Adiponectin / analysis
  • Adiponectin / metabolism
  • Adipose Tissue / cytology
  • Adult
  • Antigens, CD / metabolism
  • Cell Differentiation / drug effects*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Hyaluronic Acid / chemistry
  • Hyaluronic Acid / pharmacology*
  • Leptin / analysis
  • Leptin / metabolism
  • Lipoprotein Lipase / metabolism
  • Microscopy, Fluorescence
  • Middle Aged
  • Molecular Weight
  • PPAR gamma / metabolism
  • Phenotype
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Surgery, Plastic


  • Adiponectin
  • Antigens, CD
  • Leptin
  • PPAR gamma
  • Hyaluronic Acid
  • Lipoprotein Lipase