Vascular and perivascular niches, but not the osteoblastic niche, are numerically restored following allogeneic hematopoietic stem cell transplantation in patients with aplastic anemia

Int J Hematol. 2017 Jul;106(1):71-81. doi: 10.1007/s12185-017-2217-1. Epub 2017 Mar 16.

Abstract

Bone marrow (BM) niches, including the osteoblastic, vascular, and perivascular niches, are numerically impaired in patients with aplastic anemia (AA). It remains unclear whether these niches are numerically restored in AA patients after allogenic hematopoietic stem cell transplantation (allo-HSCT). To investigate changes in BM niches, we monitored 52 patients with AA who had undergone allo-HSCT and performed immunohistochemical studies of BM niches using antibodies against CD34, CD146, and osteopontin. After allo-HSCT, patients with AA exhibited a remarkable increase in the number of cellular elements in the BM niches, including the vascular and perivascular cells. However, no significant differences in endosteal cells were detected. We explored the cause of this restoration by analyzing the origin of BM mesenchymal stem cells (BM-MSCs) and the expression of cytokines in BM plasma. STR-PCR revealed that the BM-MSCs were derived from the host, not the donor. In addition, significantly elevated levels of vascular endothelial growth factor (VEGF) were found after allo-HSCT. Our data indicates that vascular and perivascular niches are numerically restored, but the endosteal niche remains numerically impaired in patients with AA after allo-HSCT, and that levels of VEGF, but not donor-derived BM-MSCs, may correlate with the restoration of BM niches.

Keywords: Allo-HSCT; Aplastic anemia; Bone marrow niche.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anemia, Aplastic / metabolism*
  • Anemia, Aplastic / pathology*
  • Anemia, Aplastic / therapy
  • Biomarkers
  • Bone Marrow / metabolism*
  • Bone Marrow / pathology*
  • Bone Marrow Cells / metabolism*
  • Bone Marrow Cells / pathology
  • Case-Control Studies
  • Cellular Microenvironment*
  • Cytokines / blood
  • Cytokines / metabolism
  • Female
  • Graft Survival
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / prevention & control
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cells
  • Humans
  • Immunohistochemistry
  • Immunophenotyping
  • Male
  • Middle Aged
  • Phenotype
  • Tissue Donors
  • Transplantation Chimera
  • Transplantation Conditioning
  • Transplantation, Homologous
  • Young Adult

Substances

  • Biomarkers
  • Cytokines