Effect of transplantation of adipose-derived multipotent mesenchymal stromal cells on the nervous tissue and behavioral responses in a mouse model of periventricular leukomalacia

Home/2015, Vol. 3, No. 1/Effect of transplantation of adipose-derived multipotent mesenchymal stromal cells on the nervous tissue and behavioral responses in a mouse model of periventricular leukomalacia

Cell and Organ Transplantology. 2015; 3(1): 68-73.
DOI: 10.22494/COT.V3I1.22

Effect of transplantation of adipose-derived multipotent mesenchymal stromal cells on the nervous tissue and behavioral responses in a mouse model of periventricular leukomalacia

Tsupykov O. M.1,2, Kyryk V. M.2, Ustymenko A. M.2, Yatsenko K. V.1, Butenko G. M.2, Skybo G. G.1,2
1Bogomoletz Institute of Physiology NAS Ukraine, Кyiv, Ukraine
2State Institute of Genetic and Regenerative Medicine NAMS Ukraine, Kyiv, Ukraine

Abstract
The study of opportunities to use stem cells of different origins in the treatment and rehabilitation of patients with perinatal pathology of the central neural system (CNS) is important.
The aim of our study was to evaluate the effects of transplantation of multipotent mesenchymal stromal cells (MMSСs) from adipose tissue in mice with experimental model of cerebral palsy – periventricular leukomalacia (PVL).
Materials and methods. PVL was modeled by unilateral coagulation of common carotid artery in mice line FVB on sixth day after birth followed by exposure to hypoxia (6 % O2) with intraperitoneal injection of the endotoxin lipopolysaccharide 1 mg/kg. For transplantation we used MMSСs from adipose tissue of the 2nd passage derived from mice FVB-Cg-Tg(GFPU)5Nagy/J. Syngeneic transplantation of GFP-positive MMSСs suspension into seven-day-old (P7) animals with a model of perinatal brain damage was performed stereotactically into right hemisphere in 24 hours after PVL. Corticospinal function of the control animals and the mice with PVL was assessed by testing reaching and retrieval of food rewards.
Results. After modeling PVL operated animals lagged in development, had less weight, height and disorders of static and kinetic reflex compared to non-operated control mice. Animals with PVL had lower rates of successful attempts at obtaining food: the percentage of successful attempts in control animals was 58 ± 3 % and in animals with PVL – 23 ± 4 %. In the group of animals with MMSСs transplantation after PVL modeling corticospinal function recovery was observed and the number of successful attempts was 43 ± 4 %.
Conclusions. Syngeneic stereotactic transplantation of multipotent mesenchymal stromal cells from adipose tissue contributes to the restoration of behavioral responses in animals after PVL and improves cytoarchitectonics in the focus of brain damage

Keywords: periventricular leukomalacia; adipose-derived multipotent mesenchymal stromal cells; cell transplantation

Full Text PDF

1. Yakunin JuA, Yampolskaya EI, Kipnis SL, et al. Bolezni nervnoj sistemy u novorozhdennyh i detej rannego vozrasta [Diseases of the nervous system in infants and young children]. Мoskva, Medicina, 1979. 277 s. – Moskow, Medicine, 1979. 277 p.
2. Gano D, Andersen SK, Partridge JC, et al. Diminished white matter injury over time in a cohort of premature newborns. J. Pediatr. 2015; 166(1):39–43.
https://doi.org/10.1016/j.jpeds.2014.09.009
PMid:25311709 PMCid:PMC4274204
3. Skvortsov IA, Yermolenko NA. Razvitie nervnoj sistemy u detej v norme i patologii [Development of the nervous system in children in health and pathology]. Moskva, Medpress-inform , 2003. 368 s. – Moskow, Medpress-inform, 2003. 368 p.
4. Knuesel I, Chicha L, Britschgi M, et al. Maternal immune activation and abnormal brain development across CNS disorders. Nat. Rev. Neurol. 2014; 10(11):643– 660.
5. Launay E, Gras-Le Guen C, Martinot A, et al. Why children with severe bacterial infection die: a population-based study of determinants and consequences of suboptimal care with a special emphasis on methodological issues. PLoS One. 2014; 9(9):е107286.
6. Wang LW, Lin YC, Wang ST, et al. Hypoxic/ischemic and infectious events have cumulative effects on the risk of cerebral palsy in very-low-birth-weight preterm infants. Neonatology. 2014; 106(3):209–215.
https://doi.org/10.1159/000362782
PMid:25012626
7. Velthoven CTJ, Kavelaars A, Heijnen CJ. Mesenchymal stem cells as a treatment for neonatal ischemic brain damage. Pediatric Research. 2012; 71(4):474–481.
https://doi.org/10.1038/pr.2011.64
PMid:22430383
8. Berger R, Söder S. Neuroprotection in Preterm Infants. BioMed. Research International. 2015; 2015:Article ID 257139, 14 pages.
9. Zali A, Arab L, Ashrafi F, et al. Intrathecal injection of CD133-positive enriched bone marrow progenitor cells in children with cerebral palsy: feasibility and safety. Cytotherapy. 2015; 17(2):232–241.
https://doi.org/10.1016/j.jcyt.2014.10.011
PMid:25593079
10. Wang X, Hu H, Hua R, et al. Effect of umbilical cord mesenchymal stromal cells on motor functions of identical twins with cerebral palsy: pilot study on the correlation of efficacy and hereditary factors. Cytotherapy. 2015; 17(2):224–231.
https://doi.org/10.1016/j.jcyt.2014.09.010
PMid:25593078
11. Tsai HL, Deng WP, Lai WF, et al. Wnts enhance neurotrophin-induced neuronal differentiation in adult bone-marrow-derived mesenchymal stem cells via canonical and noncanonical signaling pathways. PLoS One. 2014; 9(8):e104937.
12. Isik S, Zaim M, Yildiz MT, et al. DNA topoisomerase IIβ as a molecular switch in neural differentiation of mesenchymal stem cells. Ann. Hematol. 2015; 94(2):7–18.
13. Ahn SY, Chang YS, Park WS. Mesenchymal stem cells transplantation for neuroprotection in preterm infants with severe intraventricular hemorrhage. Korean J. Pediatr. 2014; 57(6):251–256.
14. Chernykh ER, Kafanova MY, Shevela EY, et al. Clinical experience with autologous M2 macrophages in children with severe cerebral palsy. Cell Transplant. 2014; 23(1):S97–104.
15. Clowry GJ, Basuodan R, Chan F. What are the best animal models for testing early intervention in cerebral palsy? Frontiers in Neurology. 2014; 5:Article 258, 17 pages.
16. Shen Y, Plane JM, Deng W. Mouse Models of Periventricular Leukomalacia J. Vis. Exp. 2010; 39:e1951.
17. Velthoven CTJ, Kavelaars A, Bel F, et al. Mesenchymal stem cell treatment after neonatal hypoxic-ischemic brain injury improves behavioral outcome and induces neuronal and oligodendrocyte regeneration. Brain, Behavior, and Immunity. 2010; 24(3):387–393.
https://doi.org/10.1016/j.bbi.2009.10.017
PMid:19883750
18. Lee JA, Kim BI, Jo CH, et al. Mesenchymal stem-cell transplantation for hypoxic-ischemic brain injury in neonatal rat model. Pediatric Research. 2010; 67(1):42–46.
https://doi.org/10.1203/PDR.0b013e3181bf594b
PMid:19745781
19. Velthoven CTJ, Kavelaars A, Bel F, et al. Mesenchymal stem cell transplantation changes the gene expression profile of the neonatal ischemic brain. Brain, Behavior, and Immunity. 2011; 25(7):1342–1348.
https://doi.org/10.1016/j.bbi.2011.03.021
PMid:21473911
20. Kobayashi T, Ahlenius H, Thored P, et al. Intracerebral infusion of glial cell line-derived neurotrophic factor promotes striatal neurogenesis after stroke in adult rats. Stroke. 2006; 37(9):2361–2367.
https://doi.org/10.1161/01.STR.0000236025.44089.e1
PMid:16873711
21. Shen LH, Li Y, Chopp M. Astrocytic endogenous glial cell derived neurotrophic factor production is enhanced by bone marrow stromal cell transplantation in the ischemic boundary zone after stroke in adult rats. Glia. 2010; 58(9):1074–1081.
https://doi.org/10.1002/glia.20988
PMid:20468049 PMCid:PMC3096459
22. Velthoven CTJ, Kavelaars A, Bel F, et al. Repeated mesenchymal stem cell treatment after neonatal hypoxia-ischemia has distinct effects on formation and maturation of new neurons and oligodendrocytes leading to restoration of damage, corticospinal motor tract activity, and sensorimotor function. The Journal of Neuroscience. 2010; 30(28):9603–9611.
https://doi.org/10.1523/JNEUROSCI.1835-10.2010
PMid:20631189
23. Shen LH, Li Y, Gao Q, et al. Down-regulation of neurocan expression in reactive astrocytes promotes axonal regeneration and facilitates the neurorestorative effects of bone marrow stromal cells in the ischemic rat brain. Glia. 2008; 56(16):1747–1754.
https://doi.org/10.1002/glia.20722
PMid:18618668 PMCid:PMC2575136
24. Ekdahl CT, Kokaia Z, Lindvall O. Brain inflammation and adult neurogenesis: the dual role of microglia. Neuroscience. 2009; 158(3):1021–1029.
https://doi.org/10.1016/j.neuroscience.2008.06.052
PMid:18662748
25. Czeh M, Gressens P, Kaindl AM. The yin and yang of microglia. Developmental Neuroscience. 2011; 33(3-4):199–209.
26. Thored P, Heldmann U, Gomes-Leal W, et al. Long-term accumulation of microglia with proneurogenic phenotype concomitant with persistent neurogenesis in adult subventricular zone after stroke. Glia. 2009; 57(8):35–849.
https://doi.org/10.1002/glia.20810
PMid:19053043
27. Jellema RK, Wolfs TGAM, Passos V, et al. Mesenchymal stemcells induceT-cell tolerance and protect the pretermbrain after global hypoxia-ischemia PLoS ONE. 2013; 8(8):e73031.

Tsupykov OM, Kyryk VM, Ustymenko AM, Yatsenko KV, Butenko GM, Skybo GG. Effect of transplantation of adipose-derived multipotent mesenchymal stromal cells on the nervous tissue and behavioral responses in a mouse model of periventricular leukomalacia. Cell and Organ Transplantology. 2015; 3(1):68-73. doi: 10.22494/COT.V3I1.22

 

Creative Commons License
Is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.