Adipose-Derived Stem Cells Decrease Bone Morphogenetic Protein Type 2-Induced Inflammation In Vivo

J Oral Maxillofac Surg. 2016 Mar;74(3):505-14. doi: 10.1016/j.joms.2015.09.006. Epub 2015 Sep 21.

Abstract

Purpose: Recombinant human bone morphogenetic protein type 2 (rhBMP-2) has been used to promote bone regeneration. In contrast, some reports have suggested rhBMP-2 does not provide advantages over autogenous bone grafting owing to the undesirable postoperative symptoms of this growth factor. Because the undesirable symptoms of rhBMP-2 are usually promoted by inflammation, this study evaluated the in vivo effect of human adipose-derived stem cells (ASCs) incorporated into polylactic co-glycolic acid (PLGA) scaffolds in decreasing the inflammatory response induced by a low dose of rhBMP-2.

Materials and methods: PLGA scaffolds were characterized and loaded with rhBMP-2 1, 2.5, or 5 μg per scaffold (n = 6) and the in vitro released protein amounts were quantified at 7 hours and 1, 7, and 21 days after loading (n = 3). The muscle tissue of 6 beagles received the following treatments: PLGA, PLGA plus rhBMP-2 (2.5 μg), and PLGA plus rhBMP-2 plus ASCs (1 × 10(6) ASCs). The samples were evaluated 45 days after surgery. Statistical analyses were performed and the P value was set at .05.

Results: PLGA plus rhBMP-2 plus ASCs yielded the smallest number of inflammatory foci (P < .001) and giant cells (P < .001) and the largest number of angiogenesis sites (P < .001).

Conclusions: Human ASCs administered in vivo into PLGA scaffolds with a low dose of rhBMP-2 decrease tissue inflammation and increase angiogenesis in muscular sites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorbable Implants
  • Adipose Tissue / cytology*
  • Animals
  • Biocompatible Materials / chemistry
  • Bone Morphogenetic Protein 2 / immunology
  • Bone Morphogenetic Protein 2 / therapeutic use*
  • Cell Culture Techniques
  • Cell Survival / drug effects
  • Dogs
  • Giant Cells / drug effects
  • Giant Cells / pathology
  • Humans
  • Inflammation
  • Lactic Acid / chemistry
  • Mesenchymal Stem Cells / physiology*
  • Muscle, Skeletal / blood supply
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / surgery
  • Neovascularization, Physiologic / drug effects
  • Neovascularization, Physiologic / physiology
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Recombinant Proteins / immunology
  • Recombinant Proteins / therapeutic use
  • Time Factors
  • Tissue Scaffolds / chemistry
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / therapeutic use*
  • Young Adult

Substances

  • Biocompatible Materials
  • Bone Morphogenetic Protein 2
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • recombinant human bone morphogenetic protein-2
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid