Distinct Repopulation Activity in Hu-Mice Between CB- and LPB-CD34 Cells by Enrichment of Transcription Factors

Int J Stem Cells. 2021 May 30;14(2):203-211. doi: 10.15283/ijsc21015.


Background and objectives: Human CD34 hematopoietic stem cells can reconstitute the human hematopoietic system when transplanted into immunocompromised mice after irradiation. Human leukapheresis peripheral blood (LPB)- and cord blood (CB)-derived CD34 cells have a similar capacity to reconstitute myeloid lineage cells in a humanized mice (hu-mice) model. However, potent stem cells, such as CB-CD34 cells, efficiently reconstitute the lymphoid system in vivo compared to LPB-CD34 cells. Modeling the human hematolymphoid system is vital for studying immune cell crosstalk in human xenografted mice, with CB-CD34 cells used as an optimized cell source because they are essential in reconstituting lymphoid lineage cells.

Methods and results: In this study, we established hu-mice that combined human characteristics with long-term survival and investigated the efficiency of the engraftment of lymphoid lineage cells derived from LPB- and CB-CD34 cells in the bone marrow, spleen, and LPB. We found an overall increase in the transcriptional activity of lymphoid lineage genes in CB-CD34 cells. Our results revealed that potent CB-CD34 cells displaying a general upregulation of the expression of genes involved in lymphopoiesis could contribute to the hematolymphoid system in the humanized mice model with longevity.

Conclusions: Our data suggest that humanized mouse model by usage of CB-CD34 cells displaying high expression of TFs for lymphoid lineage cells can contribute to study the immune response against lymphocytes.

Keywords: Cord blood CD34+ cells; Hematolymphoid lineage cells; Humanized mice model; Transcription factor enrichment.