Pentaisomaltose, an Alternative to DMSO. Engraftment of Cryopreserved Human CD34+ Cells in Immunodeficient NSG Mice

Research output: Contribution to journalArticle

Abstract

Hematopoietic stem cell transplantation often involves the cryopreservation of stem cell products. Currently, the standard cryoprotective agent (CPA) is dimethyl sulfoxide (DMSO), which is known to cause concentration-related toxicity and side effects when administered to patients. Based on promising in vitro data from our previous study using pentaisomaltose (a 1 kDa subfraction of Dextran 1) as an alternative to DMSO for cryopreservation of hematopoietic progenitor cells (HPCs) from apheresis products, we proceeded to a preclinical model and compared the two CPAs with respect to engraftment of human hematopoietic stem and progenitor cells (HSPCs) in the immunodeficient NSG mouse model. Human HPCs from apheresis products were cryopreserved with either pentaisomaltose or DMSO, and the following outcomes were measured: (1) the post-thaw recovery of cryopreserved cells and clonogenic potential of CD34+ cells and (2) hematopoietic engraftment in NSG mice. We found that recovery and colony-forming cells data were comparable between pentaisomaltose and DMSO. The engraftment data revealed comparable human CD45+ levels in peripheral blood at 8 weeks and bone marrow at 16 weeks post transplantation. Additionally, the frequencies of CD34+CD38low/negative and myeloid/lymphoid cells in the bone marrow were comparable. We here demonstrated that long-term engrafting HSPCs were well preserved in pentaisomaltose and comparable to cells cryopreserved with DMSO. Although a clinical trial is necessary to translate these results into human use, the present data represent an important step toward the replacement of DMSO with a non-toxic alternative.

Details

Authors
  • Jesper Dyrendom Svalgaard
  • Mehrnaz Safaee Talkhoncheh
  • Eva Kannik Haastrup
  • Lea Munthe-Fog
  • Christian Clausen
  • Morten Bagge Hansen
  • Pernille Andersen
  • Jette Sønderskov Gørløv
  • Jonas Larsson
  • Anne Fischer-Nielsen
Organisations
External organisations
  • Copenhagen University Hospital
  • Bioneer A/S
  • Herlev Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology

Keywords

  • CD34 cells, cryopreservation, cryoprotective agent, DMSO, hematopoietic progenitor cells, pentaisomaltose
Original languageEnglish
Pages (from-to)1407-1412
Number of pages6
JournalCell Transplantation
Volume27
Issue number9
Publication statusPublished - 2018
Publication categoryResearch
Peer-reviewedYes