G-CSF and hypoxic conditioning improve the proliferation, neural differentiation and migration of canine bone marrow mesenchymal stem cells

Yu,Jing; Liu,Xing‑Long; Cheng,Qi‑Guang; Lu,Shan‑Shan; Xu,Xiao‑Quan; Zu,Qing‑Quan; Liu,Sheng

doi:10.3892/etm.2016.3535

G-CSF and hypoxic conditioning improve the proliferation, neural differentiation and migration of canine bone marrow mesenchymal stem cells

Authors:
- Jing Yu
- Xing‑Long Liu
- Qi‑Guang Cheng
- Shan‑Shan Lu
- Xiao‑Quan Xu
- Qing‑Quan Zu
- Sheng Liu
View Affiliations

Affiliations: Department of Radiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Radiology, Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei 430074, P.R. China
Published online on: July 20, 2016 https://doi.org/10.3892/etm.2016.3535
Pages: 1822-1828

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Transplantation using bone marrow mesenchymal stem cells (BMSCs) is emerging as a potential regenerative therapy after ischemic attacks in the brain. However, it has been questioned because very few transplanted BMSCs are detected homing to and survived in the ischemic region. Improving the cell viability and migration ability under the complex ischemic condition seems very important. The aim of our study is to identify whether hypoxic condition and granulocyte colony-stimulating factor (G‑CSF) could improve the cell survival and migration ability of transplanted cells or hypoxic condition could promote BMSC's neural differentiation. BMSCs were treated under either normoxic (21% O2) or hypoxic (1% O2) (HP-BMSCs) conditions, no significant apoptosis was observed in hypoxic precondition (HP) group, our study confirmed that HP improves BMSCs proliferation and migration. Meanwhile, neural induction of BMSCs under hypoxic condition exhibited significant superior results than normoxic condition. Additionally, the addition of G‑CSF in HP‑BMSCs culture media promoted HP efficiency on BMSCs. These findings shed light on novel efficient strategy on the prosperity of BMSCs. Hypoxic preconditioning and cultured with G‑CSF may become a promising therapeutics for cell‑based therapy in the treatments of ischemia stroke.

View Figures

View References

1	Chen Y, Teng FY and Tang BL: Coaxing bone marrow stromal mesenchymal stem cells towards neuronal differentiation: Progress and uncertainties. Cell Mol Life Sci. 63:1649–1657. 2006. View Article : Google Scholar : PubMed/NCBI
2	Phinney DG and Isakova I: Plasticity and therapeutic potential of mesenchymal stem cells in the nervous system. Curr Pharm Des. 11:1255–1265. 2005. View Article : Google Scholar : PubMed/NCBI
3	Tse WT, Pendleton JD, Beyer WM, Egalka MC and Guinan EC: Suppression of allogeneic T-cell proliferation by human marrow stromal cells: Implications in transplantation. Transplantation. 75:389–397. 2003. View Article : Google Scholar : PubMed/NCBI
4	Nemeth K and Mezey E: Bone marrow stromal cells as immunomodulators. A primer for dermatologists. J Dermatol Sci. 77:11–20. 2015. View Article : Google Scholar : PubMed/NCBI
5	White BC, Sullivan JM, DeGracia DJ, O'Neil BJ, Neumar RW, Grossman LI, Rafols JA and Krause GS: Brain ischemia and reperfusion: Molecular mechanisms of neuronal injury. J Neurol Sci. 179:1–33. 2000. View Article : Google Scholar : PubMed/NCBI
6	Sharp FR, Ran R, Lu A, Tang Y, Strauss KI, Glass T, Ardizzone T and Bernaudin M: Hypoxic preconditioning protects against ischemic brain injury. NeuroRx. 1:26–35. 2004. View Article : Google Scholar : PubMed/NCBI
7	Theus MH, Wei L, Cui L, Francis K, Hu X, Keogh C and Yu SP: In vitro hypoxic preconditioning of embryonic stem cells as a strategy of promoting cell survival and functional benefits after transplantation into the ischemic rat brain. Exp Neurol. 210:656–670. 2008. View Article : Google Scholar : PubMed/NCBI
8	Weaver CH, Buckner CD, Longin K, Appelbaum FR, Rowley S, Lilleby K, Miser J, Storb R, Hansen JA and Bensinger W: Syngeneic transplantation with peripheral blood mononuclear cells collected after the administration of recombinant human granulocyte colony-stimulating factor. Blood. 82:1981–1984. 1993.PubMed/NCBI
9	Chiba Y, Kuroda S, Osanai T, Shichinohe H, Houkin K and Iwasaki Y: Impact of ageing on biological features of bone marrow stromal cells (BMSC) in cell transplantation therapy for CNS disorders: Functional enhancement by granulocyte-colony stimulating factor (G-CSF). Neuropathology. 32:139–148. 2012. View Article : Google Scholar : PubMed/NCBI
10	Lu SS, Liu S, Zu QQ, Xu XQ, Yu J, Wang JW, Zhang Y and Shi HB: In vivo MR imaging of intraarterially delivered magnetically labeled mesenchymal stem cells in a canine stroke model. PLoS One. 8:e549632013. View Article : Google Scholar : PubMed/NCBI
11	González MN, Dey N, Garg NJ and Postan M: Granulocyte colony-stimulating factor partially repairs the damage provoked by Trypanosoma cruzi in murine myocardium. Int J Cardiol. 168:2567–2574. 2013. View Article : Google Scholar : PubMed/NCBI
12	Schäbitz WR, Kollmar R, Schwaninger M, Juettler E, Bardutzky J, Schölzke MN, Sommer C and Schwab S: Neuroprotective effect of granulocyte colony-stimulating factor after focal cerebral ischemia. Stroke. 34:745–751. 2003. View Article : Google Scholar : PubMed/NCBI
13	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
14	Nandoe TR, Hurtado A, Levi AD, Grotenhuis JA and Oudega M: Bone marrow stromal cells for repair of the spinal cord: Towards clinical application. Cell Transplant. 15:563–577. 2006. View Article : Google Scholar : PubMed/NCBI
15	Li Y and Chopp M: Marrow stromal cell transplantation in stroke and traumatic brain injury. Neurosci Lett. 456:120–123. 2009. View Article : Google Scholar : PubMed/NCBI
16	Kacimi R, Chentoufi J, Honbo N, Long CS and Karliner JS: Hypoxia differentially regulates stress proteins in cultured cardiomyocytes: Role of the p38 stress-activated kinase signaling cascade, and relation to cytoprotection. Cardiovasc Res. 46:139–150. 2000. View Article : Google Scholar : PubMed/NCBI
17	Corbucci GG, Marchi A, Lettieri B and Luongo C: Mechanisms of cell protection by adaptation to chronic and acute hypoxia: Molecular biology and clinical practice. Minerva Anestesiol. 71:727–740. 2005.PubMed/NCBI
18	Wei L, Fraser JL, Lu ZY, Hu X and Yu SP: Transplantation of hypoxia preconditioned bone marrow mesenchymal stem cells enhances angiogenesis and neurogenesis after cerebral ischemia in rats. Neurobiol Dis. 46:635–645. 2012. View Article : Google Scholar : PubMed/NCBI
19	Chung DJ, Wong A, Hayashi K and Yellowley CE: Effect of hypoxia on generation of neurospheres from adipose tissue-derived canine mesenchymal stromal cells. Vet J. 199:123–130. 2014. View Article : Google Scholar : PubMed/NCBI
20	Wang Y, Fu W, Zhang S, He X, Liu Z, Gao D and Xu T: CXCR-7 receptor promotes SDF-1α-induced migration of bone marrow mesenchymal stem cells in the transient cerebral ischemia/reperfusion rat hippocampus. Brain Res. 1575:78–86. 2014. View Article : Google Scholar : PubMed/NCBI
21	Nichols JE, Niles JA, DeWitt D, Prough D, Parsley M, Vega S, Cantu A, Lee E and Cortiella J: Neurogenic and neuro-protective potential of a novel subpopulation of peripheral blood-derived CD133+ ABCG2+ CXCR4+ mesenchymal stem cells: Development of autologous cell-based therapeutics for traumatic brain injury. Stem Cell Res Ther. 4:32013. View Article : Google Scholar : PubMed/NCBI
22	Kinnaird T, Stabile E, Burnett MS, Shou M, Lee CW, Barr S, Fuchs S and Epstein SE: Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation. 109:1543–1549. 2004. View Article : Google Scholar : PubMed/NCBI