PEGylated liposomes associate with Wnt3A protein and expand putative stem cells in human bone marrow populations

Nanomedicine (Lond). 2017 Apr;12(8):845-863. doi: 10.2217/nnm-2016-0386. Epub 2017 Mar 29.

Abstract

Aim: To fabricate PEGylated liposomes which preserve the activity of hydrophobic Wnt3A protein, and to demonstrate their efficacy in promoting expansion of osteoprogenitors from human bone marrow.

Methods: PEGylated liposomes composed of several synthetic lipids were tested for their ability to preserve Wnt3A activity in reporter and differentiation assays. Single-molecule microspectroscopy was used to test for direct association of protein with liposomes.

Results: Labeled Wnt3A protein directly associated with all tested liposome preparations. However, Wnt3A activity was preserved or enhanced in PEGylated 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) liposomes but not in PEGylated 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes. PEGylated Wnt3A liposomes associated with skeletal stem cell populations in human bone marrow and promoted osteogenesis.

Conclusion: Active Wnt protein-containing PEGylated liposomes may have utility for systemic administration for bone repair.

Keywords: PEGylated liposomes; Wnt; fracture repair; liposomes; marrow stromal cells; mesenchymal stem cells; osteoprogenitors; regenerative medicine; skeletal stem cells.

MeSH terms

  • Bone Marrow Cells / drug effects
  • Cell Differentiation / drug effects*
  • Dimyristoylphosphatidylcholine / chemistry
  • Dimyristoylphosphatidylcholine / pharmacology
  • Humans
  • Liposomes / chemistry
  • Liposomes / pharmacology*
  • Osteogenesis / drug effects*
  • Phosphatidylcholines / chemistry
  • Phosphatidylcholines / pharmacology
  • Polyethylene Glycols / chemistry
  • Stem Cells / drug effects
  • Wnt3A Protein / chemistry
  • Wnt3A Protein / pharmacology*

Substances

  • Liposomes
  • Phosphatidylcholines
  • Wnt3A Protein
  • Polyethylene Glycols
  • 1,2-oleoylphosphatidylcholine
  • Dimyristoylphosphatidylcholine