Am J Blood Res 2012;2(1):71-76
Original Article
Chromosomal instability in in vitro cultured mouse hematopoietic cells
associated with oxidative stress
Alice Liu, William W. Qu, and Xia Liu, Cheng-Kui Qu
Department of Medicine, Division of Hematology/Oncology, Center for Stem Cell and Regenerative Medicine, Case
Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106.
Received November 4, 2011; accepted November 28, 2011; Epub December 15, 2011; Published January 15, 2012
Abstract: Hematopoietic stem cells (HSCs) that give rise to all blood cell types are important vehicles for cell-based and gene
therapies. After isolation from the bone marrow, HSCs are often cultured in laboratory settings for purposes of ex vivo
expansion, gene transduction, and bone marrow transplantation for the treatment of various disorders of the blood and
immune systems. Here we demonstrate that during in vitro culturing outside of hypoxic bone marrow niches, HSCs may
genetically alter even after short durations of time. Lineage- Scal-1+ c-Kit+ (LSK) cells that are enriched with HSCs revealed
significant levels of genomic instability following culture, as evidenced by the emergence of aneuploid cells. To further
determine the effects of in vitro culturing conditions, whole bone marrow cells were cultured in a hypoxic environment of 3%
oxygen, mimicking conditions within the body’s bone marrow, following which, cells proved to undergo less genetic
alterations. Proper dosages of the antioxidant N-Acetyl-Cysteine (NAC) similarly decreased occurrences of chromosomal
change. Furthermore, analysis of aged hematopoietic cells revealed enhanced in vitro normoxic culture-induced
chromosomal instability compared to that of young hematopoietic cells due to noted increased oxidative stress in aged cells.
These results reveal that in vitro cell culturing does indeed cause genomic instability in hematopoietic cells. Reduced oxygen
to physiological levels and additions of antioxidants can be employed as possible strategies to lower oxidative stress and
decrease chances of chromosomal transformation. Because hematopoietic cells are commonly processed in laboratory
settings before transplantation for patient treatment, our findings also raise a concern on the therapeutic use of cultured
hematopoietic cells. (AJBR11110002).
Keywords: Hematopoietic cells, stem cells, oxidative stress, chromosomal instability
Full Text PDF
Address all correspondence to:
Xia Liu and Chengqui Qu
Department of Medicine, Division of Hematology/Oncology
Center for Stem Cell and Regenerative Medicine
Case Comprehensive Cancer Center
Case Western Reserve University
Cleveland, OH 44106.
E-mail: xxl67@case.edu (XL); cxq6@case.edu (CKQ)
Original Article
Chromosomal instability in in vitro cultured mouse hematopoietic cells
associated with oxidative stress
Alice Liu, William W. Qu, and Xia Liu, Cheng-Kui Qu
Department of Medicine, Division of Hematology/Oncology, Center for Stem Cell and Regenerative Medicine, Case
Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106.
Received November 4, 2011; accepted November 28, 2011; Epub December 15, 2011; Published January 15, 2012
Abstract: Hematopoietic stem cells (HSCs) that give rise to all blood cell types are important vehicles for cell-based and gene
therapies. After isolation from the bone marrow, HSCs are often cultured in laboratory settings for purposes of ex vivo
expansion, gene transduction, and bone marrow transplantation for the treatment of various disorders of the blood and
immune systems. Here we demonstrate that during in vitro culturing outside of hypoxic bone marrow niches, HSCs may
genetically alter even after short durations of time. Lineage- Scal-1+ c-Kit+ (LSK) cells that are enriched with HSCs revealed
significant levels of genomic instability following culture, as evidenced by the emergence of aneuploid cells. To further
determine the effects of in vitro culturing conditions, whole bone marrow cells were cultured in a hypoxic environment of 3%
oxygen, mimicking conditions within the body’s bone marrow, following which, cells proved to undergo less genetic
alterations. Proper dosages of the antioxidant N-Acetyl-Cysteine (NAC) similarly decreased occurrences of chromosomal
change. Furthermore, analysis of aged hematopoietic cells revealed enhanced in vitro normoxic culture-induced
chromosomal instability compared to that of young hematopoietic cells due to noted increased oxidative stress in aged cells.
These results reveal that in vitro cell culturing does indeed cause genomic instability in hematopoietic cells. Reduced oxygen
to physiological levels and additions of antioxidants can be employed as possible strategies to lower oxidative stress and
decrease chances of chromosomal transformation. Because hematopoietic cells are commonly processed in laboratory
settings before transplantation for patient treatment, our findings also raise a concern on the therapeutic use of cultured
hematopoietic cells. (AJBR11110002).
Keywords: Hematopoietic cells, stem cells, oxidative stress, chromosomal instability
Full Text PDF
Address all correspondence to:
Xia Liu and Chengqui Qu
Department of Medicine, Division of Hematology/Oncology
Center for Stem Cell and Regenerative Medicine
Case Comprehensive Cancer Center
Case Western Reserve University
Cleveland, OH 44106.
E-mail: xxl67@case.edu (XL); cxq6@case.edu (CKQ)
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