PMID- 36332632
OWN - NLM
STAT- MEDLINE
DCOM- 20221216
LR  - 20230117
IS  - 2213-6711 (Electronic)
IS  - 2213-6711 (Linking)
VI  - 17
IP  - 12
DP  - 2022 Dec 13
TI  - The monoculture of cord-blood-derived CD34(+) cells by an automated, 
      membrane-based dynamic perfusion system with a novel cytokine cocktail.
PG  - 2585-2594
LID - S2213-6711(22)00502-1 [pii]
LID - 10.1016/j.stemcr.2022.10.006 [doi]
AB  - Human leukocyte antigen (HLA)-matched cord blood (CB) transplantation is a 
      procedure for the treatment of certain hematological malignancies, 
      hemoglobinopathies, and autoimmune disorders. However, one of the challenges is 
      to provide a sufficient number of T cell-depleted hematopoietic stem and 
      progenitor cells. Currently, only 4%-5% of the CB units stored in CB banks 
      contain enough CD34(+) cells for engrafting 70-kg patients. To support this 
      clinical need, we have developed an automated expansion protocol for CB-derived 
      CD34(+) cells in the Quantum system's dynamic perfusion bioreactor using a novel 
      cytokine cocktail comprised of stem cell factor (SCF), thrombopoietin (TPO), 
      fms-like tyrosine kinase 3 ligand (Flt-3L), interleukin-3 (IL-3), IL-6, glial 
      cell line-derived neurotrophic factor (GDNF), StemRegenin 1 (SR-1), and a 
      fibronectin-stromal-cell-derived factor-1 (SDF-1)-coated membrane. In an 8-day 
      expansion of a 2 x 10(6) positively selected CD34(+) cell inoculum from 3 donor 
      lineages, the mean cell harvest and cell viability were 1.02 x 10(8) cells and 
      95.5%, respectively, and the mean frequency of the CD45(+)CD34(+) immunophenotype 
      was 54.3%. The mean differentiated cell frequencies were 0.5% for lymphocytes, 
      15.8% for neutrophils, and 15.4% for platelets. These results demonstrate that 
      the automated monoculture protocol can support the expansion of CD34(+) cells 
      with minimal lymphocyte residual.
CI  - Copyright (c) 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Jones, Mark
AU  - Jones M
AD  - Research and Development, Terumo Blood and Cell Technologies, Lakewood, CO 80215, 
      USA. Electronic address: mark.jones@terumobct.com.
FAU - Cunningham, Annie
AU  - Cunningham A
AD  - Research and Development, Terumo Blood and Cell Technologies, Lakewood, CO 80215, 
      USA.
FAU - Frank, Nathan
AU  - Frank N
AD  - Research and Development, Terumo Blood and Cell Technologies, Lakewood, CO 80215, 
      USA.
FAU - Sethi, Dalip
AU  - Sethi D
AD  - Research and Development, Terumo Blood and Cell Technologies, Lakewood, CO 80215, 
      USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221103
PL  - United States
TA  - Stem Cell Reports
JT  - Stem cell reports
JID - 101611300
RN  - 0 (Cytokines)
RN  - 0 (Antigens, CD34)
RN  - 0 (Stem Cell Factor)
SB  - IM
MH  - Humans
MH  - *Fetal Blood
MH  - *Cytokines/metabolism
MH  - Hematopoietic Stem Cells/metabolism
MH  - Cell Culture Techniques/methods
MH  - Antigens, CD34/metabolism
MH  - Stem Cell Factor/pharmacology/metabolism
MH  - Perfusion
MH  - Cells, Cultured
PMC - PMC9768577
OTO - NOTNLM
OT  - GDNF
OT  - Quantum system
OT  - cord-blood-derived CD34(+) cells
OT  - expansion
OT  - fibronectin-SDF-1
OT  - perfusion membrane bioreactor
COIS- Conflict of interests M.J., A.C., N.F., and D.S. are all employees of Terumo 
      Blood and Cell Technologies, Inc. (Lakewood, CO, USA) at the time of manuscript 
      preparation.
EDAT- 2022/11/05 06:00
MHDA- 2022/12/17 06:00
PMCR- 2022/11/03
CRDT- 2022/11/04 19:43
PHST- 2022/03/04 00:00 [received]
PHST- 2022/10/05 00:00 [revised]
PHST- 2022/10/06 00:00 [accepted]
PHST- 2022/11/05 06:00 [pubmed]
PHST- 2022/12/17 06:00 [medline]
PHST- 2022/11/04 19:43 [entrez]
PHST- 2022/11/03 00:00 [pmc-release]
AID - S2213-6711(22)00502-1 [pii]
AID - 10.1016/j.stemcr.2022.10.006 [doi]
PST - ppublish
SO  - Stem Cell Reports. 2022 Dec 13;17(12):2585-2594. doi: 
      10.1016/j.stemcr.2022.10.006. Epub 2022 Nov 3.