Am J Blood Res 2012;2(3):148-159
Review Article
Benefits of hypoxic culture on bone marrow multipotent stromal cells
Chih-Chien Tsai, Tu-Lai Yew, Der-Chi Yang, Wei-Hua Huang, Shih-Chieh Hung
Institute of Clinical Medicine; Institute of Pharmacology, Faculty of Medicine, Institute of Oral Biology, Department of Dentistry,
National Yang-Ming University, Taipei 112, Taiwan; Stem Cell Laboratory, Department of Medical Research and Education;
5Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei 112, Taiwan
Received July 16, 2012; accepted September 12, 2012; Epub October 20, 2012; Published October 30, 2012
Abstract: Cultivation of cells is usually performed under atmospheric oxygen tension; however, such a condition does not
replicate the hypoxic conditions of normal physiological or pathological status in the body. Recently, the effects of hypoxia on
bone marrow multipotent stromal cells (MSCs) have been investigated. In a long-term culture, hypoxia can inhibit senescence,
increase the proliferation rate and enhance differentiation potential along the different mesenchymal lineages. Hypoxia also
modulates the paracrine effects of MSCs, causing upregulation of various secretable factors, including the vascular
endothelial growth factor and interleukin-6, and thereby promoting wound healing and diabetic fracture healing. Finally,
hypoxia plays an important role in mobilization and homing of MSCs, primarily by its ability to induce stromal cell-derived
factor-1 expression along with its receptor, CXCR4. After transplantation, an ischemic environment, that is the combination of
hypoxia and lack of nutrition, can lead to apoptosis or cell death, which can be overcome by the hypoxic preconditioning of
MSCs and overexpression of prosurvival genes like Akt, HO-1 and Hsp70. This review emphasizes that hypoxia is an
important factor in all major aspects of stem cell biology, and the mechanism involved in the hypoxic inducible
factor-1signaling pathway behind these responses is also discussed. (AJBR1207002).
Keywords: Mesenchymal stem cells, hypoxia, hypoxic preconditioning, proliferation, differentiation potential, apoptosis,
migration, engraftment, HIF-1
Address all correspondence to:
Dr. Shih-Chieh Hung, Department of Medical Research and Education, Veterans General Hospital-Taipei, 201, Sec. 2,
Shih-Pai Road, Taipei, 11217, Taiwan. Tel: +886-2-28757557 ext 118; Fax: +886-2-28265164. E-mail: hungsc@vghtpe.gov.tw
Review Article
Benefits of hypoxic culture on bone marrow multipotent stromal cells
Chih-Chien Tsai, Tu-Lai Yew, Der-Chi Yang, Wei-Hua Huang, Shih-Chieh Hung
Institute of Clinical Medicine; Institute of Pharmacology, Faculty of Medicine, Institute of Oral Biology, Department of Dentistry,
National Yang-Ming University, Taipei 112, Taiwan; Stem Cell Laboratory, Department of Medical Research and Education;
5Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei 112, Taiwan
Received July 16, 2012; accepted September 12, 2012; Epub October 20, 2012; Published October 30, 2012
Abstract: Cultivation of cells is usually performed under atmospheric oxygen tension; however, such a condition does not
replicate the hypoxic conditions of normal physiological or pathological status in the body. Recently, the effects of hypoxia on
bone marrow multipotent stromal cells (MSCs) have been investigated. In a long-term culture, hypoxia can inhibit senescence,
increase the proliferation rate and enhance differentiation potential along the different mesenchymal lineages. Hypoxia also
modulates the paracrine effects of MSCs, causing upregulation of various secretable factors, including the vascular
endothelial growth factor and interleukin-6, and thereby promoting wound healing and diabetic fracture healing. Finally,
hypoxia plays an important role in mobilization and homing of MSCs, primarily by its ability to induce stromal cell-derived
factor-1 expression along with its receptor, CXCR4. After transplantation, an ischemic environment, that is the combination of
hypoxia and lack of nutrition, can lead to apoptosis or cell death, which can be overcome by the hypoxic preconditioning of
MSCs and overexpression of prosurvival genes like Akt, HO-1 and Hsp70. This review emphasizes that hypoxia is an
important factor in all major aspects of stem cell biology, and the mechanism involved in the hypoxic inducible
factor-1signaling pathway behind these responses is also discussed. (AJBR1207002).
Keywords: Mesenchymal stem cells, hypoxia, hypoxic preconditioning, proliferation, differentiation potential, apoptosis,
migration, engraftment, HIF-1
Address all correspondence to:
Dr. Shih-Chieh Hung, Department of Medical Research and Education, Veterans General Hospital-Taipei, 201, Sec. 2,
Shih-Pai Road, Taipei, 11217, Taiwan. Tel: +886-2-28757557 ext 118; Fax: +886-2-28265164. E-mail: hungsc@vghtpe.gov.tw
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