Cell and Organ Transplantology. 2014; 2(2):148-150.
DOI: 10.22494/COT.V2I2.28
Short-term migration of transplanted Lin–Sca-1+c-kit+ hematopoietic stem cells after hippocampal ischemic injury of mice
Kyryk V. M.
The State Institute of Genetic and Regenerative Medicine NAMS Ukraine, Kyiv, Ukraine
Abstract
The study of migration and differentiation potential of different types of stem cells remains a problem for cell biology and regenerative medicine. The purpose of the study was to evaluate the ability of transplanted hematopoietic stem cells (HSC) of murine fetal liver to migrate into a zone of hippocampal ischemic injury at suboccipital intraventricular injection; and to assess their neural differentiation possibility in the early period after transplantation.
Materials and methods. We modeled an ischemic injury of the hippocampus of FVB-wt mice and after 24 hours transplanted suboccipitaly fetal liver HSC of FVB-Cg-Tg(GFPU)5Nagy/J fetuses (transgenic by GFP). Sorting of Lin–Sca-1+c-kit+ HSC fractions was performed by FACS. After 7 and 14 days we performed immunohistochemical staining of brain slices for GFP, NeuN and GFAP markers.
Results. On the 7th day after transplantation injected cells penetrated up to 100 µm from the wall of the 3rd ventricle, and on the 14th day single transplanted cells localized in the ischemic hippocampal CA1 region. Donor’s cells were round shape and did not express NeuN and GFAP markers. Features of reactive astrogliosis and neuronal death were kept in the hippocampal CA1 region of experimental animals, similar to the control group.
Conclusion. Transplanted Lin–Sca-1+c-kit+ mice fetal liver HSC are able to survive and migrate to the area of hippocampal ischemic injury, but the possibility of their neuronal or astrocyte differentiation in 14-day time was not confirmed.
Key words: hematopoietic stem cells; fetal liver; hippocampal ischemic injury
Full Text PDF (eng) Full Text PDF (ua)| 1. Mazo I, Massberg S, von Andrian U. Hematopoietic stem and progenitor cell trafficking. Trends in Immunology. 2011; 32(10):493–503. https://doi.org/10.1016/j.it.2011.06.011 PMid:21802990 PMCid:PMC3185129 |
||||
| 2. Jopling C, Boue S, Izpisua Belmonte J. C. Dedifferentiation, transdifferentiation and reprogramming: three routes to regeneration. Nature Reviews Molecular Cell Biology. 2011; 12:79-89. https://doi.org/10.1038/nrm3043 PMid:21252997 |
||||
| 3. Catacchio I, Berardi S, Reale A, et al. Evidence for Bone Marrow Adult Stem Cell Plasticity: Properties, Molecular Mechanisms, Negative Aspects, and Clinical Applications of Hematopoietic and Mesenchymal Stem Cells Transdifferentiation. Stem Cells Int. 2013; 2013: Article ID 589139, 11 p. | ||||
| 4. Eglitis M, Mezey E. Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proc Natl Acad Sci USA. 1997; 94:4080–4085. https://doi.org/10.1073/pnas.94.8.4080 PMid:9108108 PMCid:PMC20571 |
||||
| 5. Mezey E, Chandross K, Harta G, et al. Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. Science. 2000; 290:1779–1782. https://doi.org/10.1126/science.290.5497.1779 PMid:11099419 |
||||
| 6. Brazelton, T, Rossi F, Keshet G, Blau H. From marrow to brain: expression of neuronal phenotypes in adult mice. Science. 2000; 290:1775–1779. https://doi.org/10.1126/science.290.5497.1775 PMid:11099418 |
||||
| 7. Mezey E, Key S, Vogelsang G, et al. Transplanted bone marrow generates new neurons in human brains. Proc. Natl. Acad. Sci. USA. 2003; 100:1364–1369. https://doi.org/10.1073/pnas.0336479100 PMid:12538864 PMCid:PMC298778 |
||||
| 8. Cogle C, Yachnis A, Laywell E, et al. Bone marrow transdifferentiation in brain after transplantation: a retrospective study. Lancet. 2004; 363:1432–1437. https://doi.org/10.1016/S0140-6736(04)16102-3 |
||||
| 9. Castro R, Jackson K, Goodell M, et al. Failure of bone marrow cells transdifferentiate into neural cells in vivo. Science. 2002; 297:1299. https://doi.org/10.1126/science.297.5585.1299 PMid:12193778 |
||||
| 10. Chena J, Ellisona F, Keyvanfara K, et al. Enrichment of hematopoietic stem cells with SLAM and LSK markers for the detection of hematopoietic stem cell function in normal and Trp53 null mice. Exp. Hematol. 2008; 36:1236-1243. https://doi.org/10.1016/j.exphem.2008.04.012 PMid:18562080 PMCid:PMC2583137 |
||||
| 11. Massengale M, Wagers A, Vogel H, et al. Hematopoietic cells maintain hematopoietic fates upon entering the brain. J Exp Med. 2005; 201:1579–1589. https://doi.org/10.1084/jem.20050030 PMid:15897275 PMCid:PMC2212913 |
||||
| 12. Roybon L, Ma Z, Asztely F, et al. Failure of Transdifferentiation of Adult Hematopoietic Stem Cells into Neurons. Stem Cells. 2006; 24:1594–1604. https://doi.org/10.1634/stemcells.2005-0548 PMid:16556707 |
||||
| 13. Wehner T, Bontert M, Eyupoglu I, et al. Bone marrow-derived cells expressing green fluorescent protein under the control of the glial fibrillary acidic protein promoter do not differentiate into astrocytes in vitro and in vivo. J Neurosci. 2003; 23:5004–5011. PMid:12832523 |
||||
| 14. Kaplan R, Psaila B, Lyden D. Niche-to-niche migration of bone-marrow-derived cells. Trends Mol Med. 2007; 13(2):72-81. https://doi.org/10.1016/j.molmed.2006.12.003 PMid:17197241 |
||||
| 15. Magnon C, Lucas D, Frenette P. Trafficking of Stem Cells. Methods Mol Biol. 2011; 750:3-24. https://doi.org/10.1007/978-1-61779-145-1_1 PMid:21618080 |
||||
Kyryk VM. Short-term migration of transplanted lin-sca-1+c-kit+ hematopoietic stem cells after hippocampal ischemic injury of mice. Cell and Organ Transplantology. 2014; 2(2):148-150. doi: 10.22494/COT.V2I2.28
