Donor Site Location Is Critical for Proliferation, Stem Cell Capacity, and Osteogenic Differentiation of Adipose Mesenchymal Stem/Stromal Cells: Implications for Bone Tissue Engineering

Int J Mol Sci. 2018 Jun 26;19(7):1868. doi: 10.3390/ijms19071868.

Abstract

Human adipose mesenchymal stem/stromal cells (Ad-MSCs) have been proposed as a suitable option for bone tissue engineering. However, donor age, weight, and gender might affect the outcome. There is still a lack of knowledge of the effects the donor tissue site might have on Ad-MSCs function. Thus, this study investigated proliferation, stem cell, and osteogenic differentiation capacity of human Ad-MSCs obtained from subcutaneous fat tissue acquired from different locations (abdomen, hip, thigh, knee, and limb). Ad-MSCs from limb and knee showed strong proliferation despite the presence of osteogenic stimuli, resulting in limited osteogenic characteristics. The less proliferative Ad-MSCs from hip and thigh showed the highest alkaline phosphatase (AP) activity and matrix mineralization. Ad-MSCs from the abdomen showed good proliferation and osteogenic characteristics. Interestingly, the observed differences were not dependent on donor age, weight, or gender, but correlated with the expression of Sox2, Lin28A, Oct4α, and Nanog. Especially, low basal Sox2 levels seemed to be pivotal for osteogenic differentiation. Our data clearly show that the donor tissue site affects the proliferation and osteogenic differentiation of Ad-MSCs significantly. Thus, for bone tissue engineering, the donor site of the adipose tissue from which the Ad-MSCs are derived should be adapted depending on the requirements, e.g., cell number and differentiation state.

Keywords: AP activity; matrix mineralization; primary human adipose-derived mesenchymal stem/stromal cells (Ad-MSCs); proliferation.

MeSH terms

  • Adipose Tissue / cytology*
  • Alkaline Phosphatase / metabolism
  • Antigens, CD / metabolism
  • Bone Matrix / metabolism
  • Bone and Bones / physiology*
  • Calcification, Physiologic
  • Cell Differentiation*
  • Cell Proliferation
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Female
  • Hip
  • Humans
  • Male
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Middle Aged
  • Osteogenesis*
  • Sp7 Transcription Factor / genetics
  • Sp7 Transcription Factor / metabolism
  • Thigh
  • Tissue Donors*
  • Tissue Engineering / methods*

Substances

  • Antigens, CD
  • Core Binding Factor Alpha 1 Subunit
  • Sp7 Transcription Factor
  • Alkaline Phosphatase