Blood Science (Aug 2019)

Interleukin-12 supports in vitro self-renewal of long-term hematopoietic stem cells

  • Shanshan Zhang,
  • Maiko Morita,
  • Zhao Wang,
  • Jun Ooehara,
  • Sen Zhang,
  • Miner Xie,
  • Haitao Bai,
  • Wenying Yu,
  • Xiaofang Wang,
  • Fang Dong,
  • Jinhong Wang,
  • Shihui Ma,
  • Satoshi Yamazaki,
  • Hideo Ema

DOI
https://doi.org/10.1097/BS9.0000000000000002
Journal volume & issue
Vol. 1, no. 1
pp. 92 – 101

Abstract

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Abstract. Hematopoietic stem cells (HSCs) self-renew or differentiate through division. Cytokines are essential for inducing HSC division, but the optimal cytokine combination to control self-renewal of HSC in vitro remains unclear. In this study, we compared the effects of interleukin-12 (IL-12) and thrombopoietin (TPO) in combination with stem cell factor (SCF) on in vitro self-renewal of HSCs. Single-cell assays were used to overcome the heterogeneity issue of HSCs, and serum-free conditions were newly established to permit reproduction of data. In single-cell cultures, CD150+CD48−CD41−CD34−c-Kit+Sca-1+lineage− HSCs divided significantly more slowly in the presence of SCF+IL-12 compared with cells in the presence of SCF+TPO. Serial transplantation of cells from bulk and clonal cultures revealed that TPO was more effective than IL-12 at supporting in vitro self-renewal of short-term (6 months) HSCs, resulting in a biphasic reconstitution wave formation. The control of division rate in HSCs appeared to be crucial for preventing the loss of self-renewal potential from their in vitro culture.