Combination of Stem Cell Mobilized by Granulocyte-Colony Stimulating Factor and Human Umbilical Cord Matrix Stem Cell: Therapy of Traumatic Brain Injury in Rats

Document Type : Original Article

Authors

1 Cellular & Molecular Research Center, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Anatomy, Tehran University of Medical Science, Tehran, Iran

3 Department of Medical Physics, Tehran University of Medical Sciences, Tehran, Iran

4 Department of Immunology, Tehran University of Medical Sciences, Tehran, Iran

5 Department of Biotechnology and Bioscience, Milano-Bicocca University, Milan, Italy

6 Department of physiology, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Objective(s)
Clinical studies of treating traumatic brain injury (TBI) with autologous adult stem cells led us to examine the impression of a combination therapy. This was performed by intravenous injection of human umbilical cord matrix stem cell (hUCMSC-Wharton,s jelly stem cell) with bone marrow cell mobilized by granulocytecolony stimulating factor (G-CSF) in rats injured with cortical compact device.
Materials and Methods
Adult male Wistar rats (n= 50) were injured with controlled cortical impact device and divided into five groups. All injections were performed 1 day after injury into the tail veins of rats. Neurological functional evaluation of animals was performed before and after injury using modified neurological severity scores (mNSS). Animals were sacrificed 42 days after TBI and brain sections were stained by Brdu immunohistochemistry.
Results
Statistically significant improvement in functional outcome was observed in treatment groups when compared with control (P< 0.01). mNSS showed no significant differences among the hUCMSC and G-CSF treated groups at any time point (end of trial). Rats with hUCMSC + G-CSF treatment had a significant improvement on mNSS at 5 and 6 week compared to other treatment group (P< 0.01).
Conclusion
Histological analysis in G-CSF+ hUCMSC treated traumatic rats exhibited significant increase in numbers of Brdu immunoreactive cells in their traumatic core compared with other labeled group.

Keywords

References

1. Lu D, Mahmood A, Chopp M. Biological transplantation and neurotrophic induced neuroplasticity after traumatic brain injury. J Head Trauma Rehabil 2003;18:357-376.
2. Lu D, Mahmood A, Li Y, Chopp M. Adult bone marrow stromal cells administered intravenously to rats after traumatic brain injury migrate into brain and improve neurological outcome. Neuroreport 2001; 12:559-563.
3. Mahmood A, Lu D, Chopp M. Intravenous administration of marrow stromal cells (MSCs) increases the expression of growth factors in rat brain after traumatic brain injury. J Neurotrauma 2004; 21:33-39.
4. Mahmood A, Lu D, Li Y, Chen JL, Chopp M. Intracranial bone marrow transplantation after traumatic brain injury improves functional outcome in adult rats. J Neurosurg 2001; 94:589-595.
5. Mahmood A, Lu D, Li Y, Chopp M. Intracerebral transplantation of marrow stromal cells cultured with neurotrophic factors promotes functional recovery in adult rats subjected to traumatic brain injury. J Neurotrauma 2002; 19:1609-1617. 
6. Mahmood A, Lu D, Lu M, Chopp M. Treatment of traumatic brain injury in adult rat with intravenous administration of human bone marrow stromal cells. Neurosurgery 2003; 53:697-702.
7. Memberg SP, Hall AK. Proliferation, differentiation, and survival of rat sensory neuron precursors in vitro require specific trophic factors. Mol Cell Neurosci 1995; 6:323-335.
8. Poo MM. Neurotrophins as synaptic modulators. Nat Rev Neurosci 2001; 2, 24-32.
9. Sugimori H, Speller H, Finklestein SP. Intravenous basic fibroblast growth factor produces a persistent reduction in infarct volume following permanent focal ischemia in rats. Neurosci Lett 2001; 300:13-16.
10. Zhang ZG , Zhang Li , Jiang Q , Zhang R , Davies K , Powers C, et al. VEGF enhances angiogenesis and promotes bloodbrain barrier leakage in the ischemic brain. J Clin Invest 2000; 106:829- 838.
11. Komine-Kobayashi M, Zhang N, Liu M, Tanaka R, Hara H, Osaka A, et al. Neuroprotective effect of recombinanthuman granulocyte colony-stimulating factor in transient focal ischemiaof mice. J Cereb Blood Flow Metab 2006; 26:402-413.
12. Schabitz WR, Kollmar R , Schwaninger M , Juettler E, Bardutzky J, Skolzke MN, et al. Neuroprotective effect of granulocyte colonystimulating factor after focal cerebral ischemia. Stroke 2003; 34:745-751.
13. Chen J, Zhang ZG, Li Y, Wang L, Xu YX, Gautam SC,et al. Intravenous administration of human bone marrow stromal cells induces angiogenesis in the ischemic boundary zone after stroke in rats. Circ Res 2003; 92:692-699.
14. Li Y, Chen J, Chen XG, Wang L, Guatam SC, Xu YX, et al. Human marrow stromal cell therapy for stroke in rat.neurotrophins and functional recovery. Neurology 2002; 59:514-523.
15. Jomura S, Uy M, Mitchell K, Dallasen R, Bode CJ, Xu Y. .Potential treatment of cerebral global ischemia with oct-4+ umbilical cord matrix cells. Stem Cells 2007; 25:98 -106.
16. Demetri GD, Griffin JD. Granulocyte colony-stimulating factor and its receptor. Blood 1991; 78:2791-2808.
17. Orlic D, Kajstura J, Chimenti S, Limana F, Jakoniuk I, Quaini F, et al. Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci U S A 2001; 98:10344-10349.
18. Weaver CH, Buckner CD, Longin K, Appelbaum FR, Rowley S, Lilleby K, et al. Syngeneic transplantation withperipheral blood mononuclear cells collected after the administration ofrecombinant human granulocyte colony-stimulating factor. Blood 1993; 82:1981-1984.
19. Mitchell KE, Weiss ML, Mitchel BM, Martin P, Davis D, Morales L, et al. Matrix cells from Wharton’s jelly form neurons and glia. Stem Cells 2003; 21:50-60.
20. Weiss ML, Mitchell KE, Hix JE, Medicetty S, El-Zarkouny SZ, Grieger D, et al.Transplantation of porcine umbilical cord matrix cells into the rat brain. Exp Neurol 2003; 182:288-299.
21. Dixon CE, Clifton GL, Lighthall JW, Yaghmai AA, Hayes RL. A controlled cortical impact model of traumatic brain injury in rat. J Neurosci Methods 1991; 39:253-262.
22. Zhang RL, Zhang ZG, Zhang L, Chopp M. Proliferation and differentiation of progenitor cells in the cortex and the subventricular zone in the adult rat after focal cerebral ischemia. Neuroscience 2001; 105:33-41.
23. Bodine DM, Seidel NE, Gale MS, Nienhuis AW, Orlic D. Efficient retrovirus transduction of mouse pluripotent hematopoietic stem cells mobilized into the peripheral blood by treatment with granulocyte colony-stimulating factor and stem cell factor. Blood 1994; 84:1482-1491.
24. Chen Y, Lomnitski L, Michaelson DM, Shohami E. Motor and cognitive deficits in apolipoprotein E-deficient mice after closed head injury. Neuroscience 1997; 80:1255-1262.
25. Kuhn H.G, Dickinson-Anson H, Gage FH. Neurogenesis in the dentategyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci 1996; 16:2027-2033
26. Chen ST, Hsu CY, Hogan EL, Maricq H, Balentine JD. A model of focal ischemic stroke in the rat: reproducible extensive cortical infarction. Stroke 1986; 17:738-743.
27. Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N, et al. Bone marrow as a potential source of hepatic oval cells. Science 1999; 284:1168-1170.
28. Stumm RK, Rummel J, Junker V, Culmsee C, Pfeiffer M, Krieglstein J, et al.
A dual role for the SDF-1/CXCR4 chemokine receptor system in adult brain: isoform-selective regulation of SDF- 1 expression modulates CXCR4-dependent neuronal plasticity and cerebral leukocyte recruitment after focal ischemia, J Neurosci 2002; 22:5865-5878.
29. Ding DC, Shyu WC, Chiang MF, Lin SZ, Chang YC, Wang HJ, et al. Enhancement of neuroplasticity through upregulation of p1-integrin in human umbilical cord-derived stromal cell implanted stroke model. Neurobiol Dis 2007; 27:339-353.
30. Jiang W, Gu W, Brannstrom T, Rosqvist R, Wester P. Cortical neurogenesis in adult rats after transient middle cerebral artery occlusion. Stroke 2001; 32:1201-1207.
31. Rice A, Reiffers J. Mobilized blood stem cells: immunophenotyping and functional characteristics. J Hematother 1992; 1:19-26.
32. Six I, Gasan G, Mura E, Bordet R. Beneficial effect of pharmacological mobilization of bone marrow in experimental cerebral ischemia. Eur J Pharmacol 2003; 458:327-328.
33. Heard SO, Fink MP, Gamelli RL, Solomkin JS, Joshi M, Trask AL, et al. Effect of prophylactic administration of recombinant human granulocyte colony stimulating factor (filgrastim) on the frequency of nosocomial infections in patients with acute traumatic brain injury or . erebral hemorrhage. The Filgra .tim Study Group. Crit Care Med 1998; 26:748-754.
34. Fukumoto Y, Miyamoto T, Okamura T, Gondo H, Iwasaki H, Horiuchi T, et al. A lgina pectoris occurring during granulocyte colony-stimulating factor-combined preparatory regimen for aut logous peripheral blood stem cell transplantation in a patient with acute myelogenousleukaemia. Br J Haematol 1997; 97:666-668.
35. Taguchi A, Soma T, Tanaka H, Kanda T, Nishimura H, Yoshikawa H, et al. Administration of CD34_ cells after stroke enhances neurogenesis via angiogenesis in a mouse model. J Clin Invest 2004; 114:330-338.
36. Medicetty S, Bledsoe AR, Fahrenholtz CB, Troyer D, Weiss ML. Transplantation of pig stem cells into rat brain: Proliferation during the first 8 weeks. Exp Neurol 2004; 1909:32- 41.
37. Ding DC, Shyu WC, Chiang MF, Lin SZ, Chang YC, Wang HJ, et al. Enhancement of neuroplasticity through upregulation of p1-integrin in human umbilical cord-derived stromal cell implanted stroke model. Neurobiol Dis 2007; 27:339-353.
38. Karim F, Lisa S, Mary BB, Martin ES, Thomas L, Damien DP. Combining schwann cell bridges and olfactory- ensheathing glia grafts with chondroitinase promotes locomotor recovery after complete transection of the spinal Cord. J Neurosci 2005; 25:1169 -1178.

Files

Share

How to cite

Statistics