Flowing cells through pulsed electric fields efficiently purges stem cell preparations of contaminating myeloma cells while preserving stem cell function.
Autologous stem cell transplantation, in the setting of hematologic malignancies such as lymphoma, improves disease-free survival if the graft has undergone tumor purging. Here we show that flowing hematopoietic cells through pulsed electric fields (PEFs) effectively purges myeloma cells without sacrificing functional stem cells. Electric fields can induce irreversible cell membrane pores in direct relation to cell diameter, an effect we exploit in a flowing system appropriate for clinical scale. Multiple myeloma (MM) cell lines admixed with human bone marrow (BM) or peripheral blood (PB) cells were passed through PEFs at 1.35 kV/cm to 1.4 kV/cm, resulting in 3- to 4-log tumor cell depletion by flow cytometry and 4.5- to 6-log depletion by tumor regrowth cultures. Samples from patients with MM gave similar results by cytometry. Stem cell engraftment into nonobese diabetic-severe combined immunodeficient (NOD/SCID)/beta2m-/- mice was unperturbed by PEFs. Flowing cells through PEFs is a promising technology for rapid tumor cell purging of clinical progenitor cell preparations.
Craiu
Abie
A
Science Research Laboratory Inc, Somerville, MA, USA.
Saito
Yoriko
Y
Limon
Ana
A
Eppich
Henry M
HM
Olson
Douglas P
DP
Rodrigues
Neil
N
Adams
Gregor B
GB
Dombkowski
David
D
Richardson
Paul
P
Schlossman
Robert
R
Choi
Peter S
PS
Grogins
Jonathan
J
O'Connor
Paula G
PG
Cohen
Kenneth
K
Attar
Eyal C
EC
Freshman
Jay
J
Rich
Rebecca
R
Mangano
Joseph A
JA
Gribben
John G
JG
Anderson
Kenneth C
KC
Scadden
David T
DT
D000818:Animals; D001769:Blood; D001853:Bone Marrow; D016465:Bone Marrow Purging / Q000379:methods*; D002469:Cell Separation / Q000379:methods*; D048429:Cell Size; D018274:Electroporation; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007937:Leukapheresis; D051379:Mice; D016688:Mice, Inbred NOD; D009101:Multiple Myeloma / Q000473:pathology*; D014182:Transplantation, Autologous / Q000379:methods