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2D to 3D Switch Boosts the Regenerative Potential of Cord Blood

Review of “Evaluating Interaction of Cord Blood Hematopoietic Stem Progenitor Cells with Functionally Integrated 3D microenvironments” from STEM CELLS Translational Medicine by Stuart P. Atkinson

While human cord blood represents a potentially important source of hematopoietic stem and progenitor cells (HSPC), current two dimensional (2D) growth conditions employed to amplify cell numbers to the level required for many regenerative applications lead to a decline in the absolute percentage of the most primitive HSPCs [1]. 

To solve this vexing problem and boost the regenerative potential of cord blood, researchers from the laboratories of Shay Soker and Graça Almeida-Porada (Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA) shifted from two dimensions to three dimensions in a recent STEM CELLS Translational Medicine article. Specifically, the authors aimed to aid the expansion or maintenance of primitive HSCs in vitro [2, 3] by recreating the three dimensional (3D) fetal liver niche, the primary site for HSPC expansion and differentiation [4], by seeding liver cells onto a 3D liver extracellular matrix. Can this 2D to 3D switch by Mokhtari et al. boost the regenerative potential of cord blood [5]?

To highlight the potentially important role of 3D culture conditions, the authors compared 2D monolayers of hepatocyte progenitors, fetal liver stromal cells, or adult bone marrow-derived stromal progenitor cells to their 3D counterparts cultured on liver extracellular matrix (3D-ECM) constructs. While the 3D-ECM alone could not support HPSC growth in vitro, each of the 3D constructs supported the maintenance of primitive HSPCs better than their 2D counterparts, irrespective of the seeded cell type. While this finding emphasized the relative importance of 3D growth conditions rather than the specific cell-type employed, the authors did highlight fetal liver stromal cells as the optimal cell line for cord blood HSPC growth and expansion.

However, while the authors have established that mimicking the in vivo 3D niche of primitive HSPCs can maintain their number during in vitro culture, they note the additional requirement for further in vivo engraftment studies to fully understand whether primitive HPSCs grown under 3D conditions retain full functionality.

To keep up to date with all the continuing studies that hope to boost the regenerative potential of cord blood, stay tuned to the Stem Cells Portal.


  1. Hao QL, Shah AJ, Thiemann FT, et al., A functional comparison of CD34 + CD38- cells in cord blood and bone marrow. Blood 1995;86:3745-53.
  2. Brummendorf TH, Dragowska W, and Lansdorp PM, Asymmetric cell divisions in hematopoietic stem cells. Ann N Y Acad Sci 1999;872:265-72; discussion 272-3.
  3. Mikkola HK and Orkin SH, The journey of developing hematopoietic stem cells. Development 2006;133:3733-44.
  4. Morrison SJ, Hemmati HD, Wandycz AM, et al., The purification and characterization of fetal liver hematopoietic stem cells. Proc Natl Acad Sci U S A 1995;92:10302-6.
  5. Mokhtari S, Baptista PM, Vyas DA, et al., Evaluating Interaction of Cord Blood Hematopoietic Stem/Progenitor Cells with Functionally Integrated Three-Dimensional Microenvironments. STEM CELLS Translational Medicine 2018;7:271-282.