Comparison of mesenchymal stromal cells from human bone marrow and adipose tissue for the treatment of spinal cord injury

Cytotherapy. 2013 Apr;15(4):434-48. doi: 10.1016/j.jcyt.2012.11.015. Epub 2013 Feb 1.

Abstract

Background aims: Bone marrow and subcutaneous adipose tissue are both considered prospective sources of mesenchymal stromal cells (MSCs), which can be used in cell therapy for spinal cord injury (SCI). The present study investigated whether human adipose tissue-derived mesenchymal stromal cells (hADSCs) transplanted into a rat model of SCI would lead to similar or improved neurologic effects compared with human bone marrow-derived mesenchymal stromal cells (hBMSCs).

Methods: hADSCs and hBMSCs were isolated from five adult donors. These MSCs were characterized using flow cytometry, immunocytochemistry, real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Immediately after SCI, 2 × 10(5) hBMSCs or hADSCs were injected into the injured spinal cord. Locomotor function, cell survival and differentiation, spinal cord tissue morphology and brain-derived neurotrophic factor (BDNF) expression were compared between groups.

Results: hADSCs and hBMSCs showed similar surface protein expression, and hADSCs showed higher proliferative activity with higher expression of vascular endothelial cell growth factor, hepatocyte growth factor and BDNF than hBMSCs. After transplant, both hADSCs and hBMSCs migrated within the injured spinal cord without differentiating into glial or neuronal elements. Administration of hADSCs was associated with marked changes in the SCI environment, with significant increases in BDNF levels. This was simultaneously associated with increased angiogenesis, preserved axons, decreased numbers of ED1-positive macrophages and reduced lesion cavity formation. These changes were accompanied by improved functional recovery.

Conclusions: The present results suggest that hADSCs would be more appropriate for transplant to treat SCI than hBMSCs.

MeSH terms

  • Adipose Tissue / cytology*
  • Animals
  • Bone Marrow Cells / cytology*
  • Brain-Derived Neurotrophic Factor / biosynthesis
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cell Differentiation
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Ectodysplasins / biosynthesis
  • Female
  • Humans
  • Macrophages / metabolism
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology*
  • Middle Aged
  • Neovascularization, Physiologic
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord / metabolism
  • Spinal Cord Injuries / therapy*

Substances

  • Brain-Derived Neurotrophic Factor
  • Ectodysplasins