Neurological Sciences

, Volume 32, Issue 4, pp 641–651

Bone marrow mesenchymal stem cells can be mobilized into peripheral blood by G-CSF in vivo and integrate into traumatically injured cerebral tissue

  • Jun Deng
  • Zhong-min Zou
  • Tao-li Zhou
  • Yong-ping Su
  • Guo-ping Ai
  • Jun-ping Wang
  • Hui Xu
  • Shi-wu Dong
Original Article

Abstract

The efficacy of granulocyte colony-stimulating factor (G-CSF) in mobilizing mesenchymal stem cells (MSCs) into peripheral blood (PB) and the ability of PB-MSCs incorporated into injured brain were tested. Colony forming, cell phenotype and differentiation potential of mouse MSCs mobilized by G-CSF (40 μg/kg) were evaluated. Mortality and pathological changes in mice with serious craniocerebral trauma plus G-CSF treatment (40 μg/kg) were investigated. Bone marrow (BM) cells derived from GFP mice were fractionated into MSCs, hematopoietic stem cells (HSCs), and non-MSC/HSCs using magnetic beads and adherent culture. The resultant cell populations were transplanted into injured mice. The in vivo integration and differentiation of the transplanted cells were detected immunocytochemically. The expression of SDF-1 in injured area of brain was tested by Western blot. G-CSF was able to mobilize MSCs into PB (fourfold increase). PB-MSCs possessed similar characteristics as BM-MSCs in terms of colony formation, the expression pattern of CD73, 44, 90, 106, 31 and 45, and multipotential of differentiation. Accumulative total mice mortality was lower in TG group (5/14) than that in T group (7/14). It was MSCs, not HSCs or non-MSC/HSC cells integrated into the damaged cerebral tissue and differentiated into cells expressing neural markers. Increased SDF-1 expression in injured area of brain was confirmed, which could facilitate the homing of MSCs to brain. G-CSF can mobilize MSCs into PB and MSCs in PB can integrate into injured cerebral tissue and transdifferentiated into neural cells and may benefit the repair of trauma.

Keywords

Mesenchymal stem cells Granulocyte colony-stimulating factor Stem cell mobilization Cell differentiation 

References

  1. 1.
    Rink A, Fung KM, Trojanowski JQ et al (1995) Evidence of apoptotic cell death after experimental traumatic brain injury in the rat. Am J Pathol 147:1575–1583PubMedGoogle Scholar
  2. 2.
    Kornblum HI (2007) Introduction to neural stem cells. Stroke 38:810–816PubMedCrossRefGoogle Scholar
  3. 3.
    Ke Y, Chi L, Xu R et al (2006) Early response of endogenous adult neural progenitor cells to acute spinal cord injury in mice. Stem Cells 24:1011–1019PubMedCrossRefGoogle Scholar
  4. 4.
    Deng J, Petersen BE, Steindler DA et al (2006) Mesenchymal stem cells spontaneously express neural proteins in culture and are neurogenic after transplantation. Stem Cells 24:1054–1064PubMedCrossRefGoogle Scholar
  5. 5.
    Coyne TM, Marcus AJ, Woodbury D et al (2006) Marrow stromal cells transplanted to the adult brain are rejected by an inflammatory response and transfer donor labels to host neurons and glia. Stem Cells 24:2483–2492PubMedCrossRefGoogle Scholar
  6. 6.
    Cheng TM, Shi CM, Su YP (2005) Spontaneous malignant transformation of adult stem cell in vitro culture proliferation. Zhonghua Yi Xue Za Zhi 85:1883–1884PubMedGoogle Scholar
  7. 7.
    Tolar J, Nauta AJ, Osborn MJ et al (2007) Sarcoma derived from cultured mesenchymal stem cells. Stem Cells 25:371–379PubMedCrossRefGoogle Scholar
  8. 8.
    Lee MW, Choi J, Yang MS et al (2004) Mesenchymal stem cells from cryopreserved human umbilical cord blood. Biochem Biophys Res Commun 320:273–278PubMedCrossRefGoogle Scholar
  9. 9.
    Gutierrez-Rodriguez M, Reyes-Maldonado E, Mayani H (2000) Characterization of the adherent cells developed in Dexter-type long-term cultures from human umbilical cord blood. Stem Cells 18:46–52PubMedCrossRefGoogle Scholar
  10. 10.
    Igura K, Zhang X, Takahashi K et al (2004) Isolation and characterization of mesenchymal progenitor cells from chorionic villi of human placenta. Cytotherapy 6:543–553PubMedCrossRefGoogle Scholar
  11. 11.
    Zvaifler NJ, Marinova-Mutafchieva L, Adams G et al (2000) Mesenchymal precursor cells in the blood of normal individuals. Arthr Res 2:477–488CrossRefGoogle Scholar
  12. 12.
    Wexler SA, Donaldson C, Denning-Kendall P et al (2003) Adult bone marrow is a rich source of human mesenchymal ‘stem’ cells but umbilical cord and mobilized adult blood are not. Br J Haematol 121:368–374PubMedCrossRefGoogle Scholar
  13. 13.
    Lazarus HM, Haynesworth SE, Gerson SL et al (1997) Human bone marrow-derived mesenchymal (stromal) progenitor cells (MPCs) cannot be recovered from peripheral blood progenitor cell collections. J Hematother 6:447–455PubMedGoogle Scholar
  14. 14.
    Schneider A, Wysocki R, Pitzer C et al (2006) An extended window of opportunity for G-CSF treatment in cerebral ischemia. BMC Biol 4:36Google Scholar
  15. 15.
    Honma T, Honmou O, Iihoshi S et al (2006) Intravenous infusion of immortalized human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat. Exp Neurol 199:56–66PubMedCrossRefGoogle Scholar
  16. 16.
    Sotnikova NV, Stavrova LA, Gur’antseva LA et al (2005) Mechanisms of the effects of granulocytic CSF on tissue reparation during chronic CCl4-induced damage to the liver. Bull Exp Biol Med 140:644–647PubMedCrossRefGoogle Scholar
  17. 17.
    Gol’dberg ED, Dygai AM, Zhdanov VV et al (2005) Effect of granulocyte colony-stimulating factor on myocardium recovery in postinfarction period. Bull Exp Biol Med 139:319–321PubMedCrossRefGoogle Scholar
  18. 18.
    Lombaert IM, Wierenga PK, Kok T et al (2006) Mobilization of bone marrow stem cells by granulocyte colony-stimulating factor ameliorates radiation-induced damage to salivary glands. Clin Cancer Res 12:1804–1812PubMedCrossRefGoogle Scholar
  19. 19.
    Takamiya M, Okigaki M, Jin D et al (2006) Granulocyte colony-stimulating factor-mobilized circulating c-Kit+/Flk-1+ progenitor cells regenerate endothelium and inhibit neointimal hyperplasia after vascular injury. Arterioscler Thromb Vasc Biol 26:751–757PubMedCrossRefGoogle Scholar
  20. 20.
    Marmarou A, Foda MA, van den Brink W et al (1994) A new model of diffuse brain injury in rats. Part I: pathophysiology and biomechanics. J Neurosurg 80:291–300PubMedCrossRefGoogle Scholar
  21. 21.
    Shyu WC, Lee YJ, Liu DD et al (2006) Homing genes, cell therapy and stroke. Front Biosci 11:899–907PubMedCrossRefGoogle Scholar
  22. 22.
    Schabitz WR, Schneider A (2006) Developing granulocyte-colony stimulating factor for the treatment of stroke: current status of clinical trials. Stroke 37:1654; author reply 1655Google Scholar
  23. 23.
    Fukuda K, Fujita J (2005) Mesenchymal, but not hematopoietic, stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction in mice. Kidney Int 68:1940–1943PubMedCrossRefGoogle Scholar
  24. 24.
    Meuer K, Pitzer C, Teismann P et al (2006) Granulocyte-colony stimulating factor is neuroprotective in a model of Parkinson’s disease. J Neurochem 97:675–686PubMedCrossRefGoogle Scholar
  25. 25.
    Kan I, Melamed E, Offen D (2007) Autotransplantation of bone marrow-derived stem cells as a therapy for neurodegenerative diseases. Handb Exp Pharmacol 180:219–242Google Scholar
  26. 26.
    Takamiya M, Fujita S, Saigusa K et al (2007) Simultaneous detections of 27 cytokines during cerebral wound healing by multiplexed bead-based immunoassay for wound age estimation. J Neurotrauma 24:1833–1844PubMedCrossRefGoogle Scholar
  27. 27.
    Klocke R, Kuhlmann MT, Scobioala S et al (2008) Granulocyte colony-stimulating factor (G-CSF) for cardio- and cerebrovascular regenerative applications. Curr Med Chem 15:968–977PubMedCrossRefGoogle Scholar
  28. 28.
    Maurer MH, Schabitz WR, Schneider A (2008) Old friends in new constellations—the hematopoetic growth factors G-CSF, GM-CSF, and EPO for the treatment of neurological diseases. Curr Med Chem 15:1407–1411PubMedCrossRefGoogle Scholar
  29. 29.
    He Q, Wan C, Li G (2007) Concise review: multipotent mesenchymal stromal cells in blood. Stem Cells 25:69–77PubMedCrossRefGoogle Scholar
  30. 30.
    Kassis I, Zangi L, Rivkin R et al (2006) Isolation of mesenchymal stem cells from G-CSF-mobilized human peripheral blood using fibrin microbeads. Bone Marrow Transplant 37:967–976PubMedCrossRefGoogle Scholar
  31. 31.
    Shi M, Li J, Liao L et al (2007) Regulation of CXCR4 expression in human mesenchymal stem cells by cytokine treatment: role in homing efficiency in NOD/SCID mice. Haematologica 92:897–904PubMedCrossRefGoogle Scholar
  32. 32.
    Ozaki K, Sato K, Oh I et al (2007) Mechanisms of immunomodulation by mesenchymal stem cells. Int J Hematol 86:5–7PubMedCrossRefGoogle Scholar
  33. 33.
    Satake K, Lou J, Lenke LG (2004) Migration of mesenchymal stem cells through cerebrospinal fluid into injured spinal cord tissue. Spine 29:1971–1979PubMedCrossRefGoogle Scholar
  34. 34.
    Guo L, Yin F, Meng HQ et al (2005) Differentiation of mesenchymal stem cells into dopaminergic neuron-like cells in vitro. Biomed Environ Sci 18:36–42PubMedGoogle Scholar
  35. 35.
    Hamada H, Kobune M, Nakamura K et al (2005) Mesenchymal stem cells (MSC) as therapeutic cytoreagents for gene therapy. Cancer Sci 96:149–156PubMedCrossRefGoogle Scholar
  36. 36.
    Hardy SA, Maltman DJ, Przyborski SA (2008) Mesenchymal stem cells as mediators of neural differentiation. Curr Stem Cell Res Ther 3:43–52PubMedCrossRefGoogle Scholar
  37. 37.
    Jackson L, Jones DR, Scotting P et al (2007) Adult mesenchymal stem cells: differentiation potential and therapeutic applications. J Postgrad Med 53:121–127PubMedCrossRefGoogle Scholar
  38. 38.
    Jeong JA, Gang EJ, Hong SH et al (2004) Rapid neural differentiation of human cord blood-derived mesenchymal stem cells. Neuroreport 15:1731–1734PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Jun Deng
    • 1
  • Zhong-min Zou
    • 1
  • Tao-li Zhou
    • 2
  • Yong-ping Su
    • 1
  • Guo-ping Ai
    • 1
  • Jun-ping Wang
    • 1
  • Hui Xu
    • 1
  • Shi-wu Dong
    • 1
  1. 1.Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, School of Preventive MedicineThird Military Medical UniversityChongqingChina
  2. 2.Department of Pathogenic Biology, School of Medical ScienceThe Third Military Medical UniversityChongqingChina

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