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

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

doi:10.1177/0963689718786226

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

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

^*Corresponding author af dette arbejde

Institut for Klinisk Medicin

6 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Cell Transplantation
Vol/bind	27
Udgave nummer	9
Sider (fra-til)	1407-1412
Antal sider	6
ISSN	0963-6897
DOI	https://doi.org/10.1177/0963689718786226
Status	Udgivet - 1 sep. 2018

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10.1177/0963689718786226Licens: CC BY-NC

Citationsformater

Svalgaard, J. D., Talkhoncheh, M. S., Haastrup, E. K., Munthe-Fog, L., Clausen, C., Hansen, M. B., Andersen, P., Gørløv, J. S., Larsson, J., & Fischer-Nielsen, A. (2018). Pentaisomaltose, an Alternative to DMSO. Engraftment of Cryopreserved Human CD34+ Cells in Immunodeficient NSG Mice. Cell Transplantation, 27(9), 1407-1412. https://doi.org/10.1177/0963689718786226

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

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.",

author = "Svalgaard, {Jesper Dyrendom} and Talkhoncheh, {Mehrnaz Safaee} and Haastrup, {Eva Kannik} and Lea Munthe-Fog and Christian Clausen and Hansen, {Morten Bagge} and Pernille Andersen and G{\o}rl{\o}v, {Jette S{\o}nderskov} and Jonas Larsson and Anne Fischer-Nielsen",

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T1 - Pentaisomaltose, an Alternative to DMSO. Engraftment of Cryopreserved Human CD34+ Cells in Immunodeficient NSG Mice

AU - Svalgaard, Jesper Dyrendom

AU - Talkhoncheh, Mehrnaz Safaee

AU - Haastrup, Eva Kannik

AU - Munthe-Fog, Lea

AU - Clausen, Christian

AU - Hansen, Morten Bagge

AU - Andersen, Pernille

AU - Gørløv, Jette Sønderskov

AU - Larsson, Jonas

AU - Fischer-Nielsen, Anne

PY - 2018/9/1

Y1 - 2018/9/1

N2 - 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.

AB - 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.

U2 - 10.1177/0963689718786226

DO - 10.1177/0963689718786226

M3 - Letter

C2 - 30056762

SN - 0963-6897

VL - 27

SP - 1407

EP - 1412

JO - Cell Transplantation

JF - Cell Transplantation

IS - 9

ER -

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

Abstract

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