Systemic transplantation of human adipose-derived stem cells stimulates bone repair by promoting osteoblast and osteoclast function

J Cell Mol Med. 2011 Oct;15(10):2082-94. doi: 10.1111/j.1582-4934.2010.01230.x.

Abstract

Systemic transplantation of adipose-derived stem cells (ASCs) is emerging as a novel therapeutic option for functional recovery of diverse damaged tissues. This study investigated the effects of systemic transplantation of human ASCs (hASCs) on bone repair. We found that hASCs secrete various bone cell-activating factors, including hepatocyte growth factor and extracellular matrix proteins. Systemic transplantation of hASCs into ovariectomized mice induced an increased number of both osteoblasts and osteoclasts in bone tissue and thereby prevented bone loss. We also observed that conditioned medium from hASCs is capable of stimulating proliferation and differentiation of osteoblasts via Smad/extracellular signal-regulated kinase (ERK)/JNK (c-jun NH(2) -terminal kinase) activation as well as survival and differentiation of osteoclasts via ERK/JNK/p38 activation in vitro. Overall, our findings suggest that paracrine factors secreted from hASCs improve bone repair and that hASCs can be a valuable tool for use in osteoporosis therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / metabolism*
  • Animals
  • Bone Regeneration / physiology*
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Culture Media, Conditioned
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression
  • Humans
  • MAP Kinase Kinase 4 / genetics
  • MAP Kinase Kinase 4 / metabolism
  • Mice
  • Osteoblasts / cytology
  • Osteoblasts / metabolism
  • Osteoclasts / cytology
  • Osteoclasts / metabolism
  • Signal Transduction
  • Stem Cell Transplantation / methods*
  • Stem Cells / cytology
  • Stem Cells / metabolism*

Substances

  • Culture Media, Conditioned
  • Extracellular Signal-Regulated MAP Kinases
  • MAP Kinase Kinase 4