Cord blood CD34+ cells expanded on Wharton's jelly multipotent mesenchymal stromal cells improve the hematopoietic engraftment in NOD/SCID mice

Eur J Haematol. 2014 Nov;93(5):384-91. doi: 10.1111/ejh.12363. Epub 2014 May 26.

Abstract

Objective: This study aims to investigate the capability of Wharton's jelly multipotent mesenchymal stromal cells (WJ-MSC) to support the in vitro expansion of hematopoietic stem/progenitor cells (HSPC) derived from cord blood (CB) in the absence of exogenous cytokines, and the effect on engraftment of the expanded cells in a mouse model.

Methods: CB-CD34+ cells were seeded on WJ-MSC layer and cultured in HP01 serum-free medium. Day-7 and day-13 expanded cells were transplanted in NOD/SCID mice. After 8 wk, engraftment was evaluated in mouse bone marrow as percentage of human CD45+ cells.

Results: CD34+ population was expanded without increasing the differentiation rate. Co-culture increased the expansion of the CD34+ cells by 2.0 and 7.3 times after 7 and 13 d, respectively, and maintained the CD34+ cells up to day 20. In particular, earlier CD34+/CD90+ and CD34+/CD33- subtypes were increased. An advantage of the day-7 co-cultured HSPC in respect of HSPC at day 0 in the engraftment of NOD/SCID mice was obtained both as percentage of mice engrafted (100% vs. 75%) and as percentage of chimerism.

Conclusions: Although the increase in hematopoietic progenitors is not dramatic as in the presence of added cytokines, this study demonstrates the effectiveness of the WJ-MSC not only to preserve the CD34+ population but also to improve the repopulating efficacy of the amplified HSPC, also in the absence of added cytokines and growth factors.

Keywords: Wharton's jelly; cord blood transplantation; hematopoietic engraftment; multipotent mesenchymal stromal cells; non-obese diabetic/severe combined immunodeficient mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD34
  • Biomarkers
  • Cell Proliferation
  • Coculture Techniques
  • Female
  • Fetal Blood / cytology*
  • Fetal Blood / metabolism
  • Gene Expression
  • Graft Survival*
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Multipotent Stem Cells / cytology*
  • Multipotent Stem Cells / metabolism
  • Transplantation Chimera
  • Transplantation, Heterologous
  • Wharton Jelly / cytology*
  • Wharton Jelly / metabolism
  • Whole-Body Irradiation

Substances

  • Antigens, CD34
  • Biomarkers