Two kinds of stem cell nasal transplantation for treating white matter injury in premature rat infants

doi:10.3969/j.issn.2095-4344.2150

Abstract

Abstract: BACKGROUND: Stem cell transplantation has a significant neuroprotective effect on neurological diseases. Current transplantation methods such as arteriovenous transplantation and brain stereotactic transplantation are not suitable for clinical application in preterm infants.
OBJECTIVE: To explore the feasibility of nasal transplantation of human umbilical cord mesenchymal stem cells and human neural stem cells for the treatment of white matter injury in premature rat infants.
METHODS: Human umbilical cord mesenchymal stem cells were prepared from human umbilical cord tissue, and human neural stem cells were prepared from human embryonic brain tissue. In vitro migration of two kinds of cells was assessed by Transwell method. Forty 3-day-old Sprague-Dawley rats were randomly divided into sham operation group, model control group, human umbilical cord mesenchymal stem cell transplantation group and human neural stem cell transplantation group, with 10 rats in each group. Rats in all groups except the sham operation group were treated with right common carotid artery ligation and hypoxia for 90 minutes to establish a rat model of white matter injury in the preterm infant. Totally 1×106 cells were delivered intranasally in the transplantation group at 3 days after injury. Each nostril was infused with 5×105, and each nostril was infused once. On day 7 after injury, MBP immunofluorescence staining was used to detect the expression of myelin basic protein in the white matter of the brain to identify the damage of the white matter injury model. At 24 hours after transplantation, human umbilical cord mesenchymal stem cell migration was detected by anti-HuNu immunohistochemical method and human neural stem cell migration was detected by CM-Dil fluorescent labeling method.
RESULTS AND CONCLUSION: (1) On day 7 after modeling, compared with the normal side, the positive area of MBP decreased in cingulate band, corpus callosum and external capsule of the affected side in the model of brain white matter injury in preterm infants (P < 0.05), indicating a successful modeling. (2) In vitro experiments showed that the migration rate of human neural stem cells was the same as that of human umbilical cord mesenchymal stem cells. (3) At 24 hours after the nasal transplantation, human umbilical cord mesenchymal stem cells migrated to the cortex, corpus callosum and hippocampus on the normal side and the damaged side, and human neural stem cells migrated to the damaged cortex, corpus callosum and hippocampus, and human umbilical cord mesenchymal stem cells migrated more than human neural stem cells. (4) Overall, these findings indicate that 24 hours after the nasal transplantation, human umbilical cord mesenchymal stem cells could survive and migrate to the normal side and the injury side, and human neural stem cells could survive and migrate to the injury side; and the migration of human umbilical cord mesenchymal stem cells was more extensive than that of human neural stem cells.

Key words: stem cells, transplantation, human umbilical cord mesenchymal stem cells, human neural stem cells, intranasal, premature infants, white matter injury, rats

CLC Number:

Zang Jing, Luan Zuo, Wang Qian, Yang Yinxiang, Wang Zhaoyan, Wu Youjia, Guo Aisong. Two kinds of stem cell nasal transplantation for treating white matter injury in premature rat infants[J]. Chinese Journal of Tissue Engineering Research, 2021, 25(1): 101-107.

Figures/Tables 6

References

[1] LIU L, OZA S, HOGAN D, et al. Global, regional, and national causes of under-5 mortality in 2000-15: an updated systematic analysis with implications for the Sustainable Development Goals. Lancet. 2016;388(10063):3027-3035.
[2] DULEY L, DORLING J, AYERS S, et al. Improving quality of care and outcome at very preterm birth: the Preterm Birth research programme, including the Cord pilot RCT. Southampton (UK). 2019.
[3] HERRERA TI, EDWARDS L, MALCOLM WF, et al. Outcomes of preterm infants treated with hypothermia for hypoxic-ischemic encephalopathy. Early Hum Dev. 2018;125:1-7.
[4] DE SIQUEIRA CALDAS JP, FERRI WAG, MARBA STM, et al. Admission hypothermia, neonatal morbidity, and mortality: evaluation of a multicenter cohort of very low birth weight preterm infants according to relative performance of the center. Eur J Pediatr. 2019;178(7): 1023-1032.
[5] GUNN AJ, BENNET L. Brain cooling for preterm infants. Clin Perinatol. 2008;35(4):735-748.
[6] Mazini L, Rochette L, Amine M, et al. Regenerative Capacity of Adipose Derived Stem Cells (ADSCs), Comparison with Mesenchymal Stem Cells (MSCs). Int J Mol Sci. 2019;20(10): E2523.
[7] WU KC, CHANG YH, LIU HW, et al. Transplanting human umbilical cord mesenchymal stem cells and hyaluronate hydrogel repairs cartilage of osteoarthritis in the minipig model. Ci Ji Yi Xue Za Zhi. 2019;31(1): 11-19.
[8] BOESE AC, LE QE, PHAM D, et al. Neural stem cell therapy for subacute and chronic ischemic stroke. Stem Cell Res Ther. 2018;9(1):154.
[9] BOESE AC, ECKERT A, HAMBLIN MH, et al. Human neural stem cells improve early stage stroke outcome in delayed tissue plasminogen activator-treated aged stroke brains. Exp Neurol. 2020;329:113275.
[10] HLADKY SB, BARRAND MA. Elimination of substances from the brain parenchyma: efflux via perivascular pathways and via the blood-brain barrier. Fluids Barriers CNS. 2018;15(1):30.
[11] VAN VELTHOVEN CT, KAVELAARS A, VAN BEL F, et al. Nasal administration of stem cells: a promising novel route to treat neonatal ischemic brain damage. Pediatr Res. 2010;68(5):419-422.
[12] YU D, LI G, LESNIAK MS, et al. Intranasal Delivery of Therapeutic Stem Cells to Glioblastoma in a Mouse Model. J Vis Exp. 2017;(124):55845.
[13] 马雪霞,汪兆艳,王倩,等.不同厚度神经球冰冻切片免疫荧光细胞化学染色结果的比较[J].细胞与分子免疫学杂志,2018,34(6): 495-498.
[14] FENG EC, JIANG L. Effects of leptin on neurocognitive and motor functions in juvenile rats in a preterm brain damage model. Mol Med Rep. 2018;18(4):4095-4102.
[15] QIAO L, FU J, XUE X, et al. Neuronalinjury and roles of apoptosis and autophagy in a neonatal rat model of hypoxia-ischemia-induced periventricular leukomalacia. Mol Med Rep. 2018;17(4):5940-5949.
[16] WANG Y, LI B, LI Z, et al. Improvement of hypoxia-ischemia-induced white matter injury in immature rat brain by ethyl pyruvate. Neurochem Res. 2013;38(4):742-752.
[17] REITZ M, DEMESTRE M, SEDLACIK J, et al. Intranasal delivery of neural stem/progenitor cells: a noninvasive passage to target intracerebral glioma. Stem Cells Transl Med. 2012;1(12):866-873.
[18] GOPAGONDANAHALLI KR, LI J, FAHEY MC, et al. Preterm Hypoxic-Ischemic Encephalopathy. Front Pediatr. 2016;4:114.
[19] SPITTLE AJ, MORGAN C, OLSEN JE, et al. Early Diagnosis and Treatment of Cerebral Palsy in Children with a History of Preterm Birth. Clin Perinatol. 2018;45(3):409-420.
[20] MOSTER D, LIE RT, MARKESTAD T. Long-term medical and social consequences of preterm birth. N Engl J Med. 2008;359(3):262-273.
[21] CORMACK BE, HARDING JE, MILLER SP, et al. The Influence of Early Nutrition on Brain Growth and Neurodevelopment in Extremely Preterm Babies: A Narrative Review. Nutrients. 2019;11(9). pii: E2029.
[22] LUNDBERG J, JUSSING E, LIU Z, et al. Safety of Intra-Arterial Injection With Tumor-Activated T Cells to the Rabbit Brain Evaluated by MRI and SPECT/CT. Cell Transplant. 2017;26(2):283-292.
[23] LIM M, WANG W, LIANG L, et al. Intravenous injection of allogeneic umbilical cord-derived multipotent mesenchymal stromal cells reduces the infarct area and ameliorates cardiac function in a porcine model of acute myocardial infarction. Stem Cell Res Ther. 2018;9(1):129.
[24] DE KEYSER J. Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol. 2005;58(4):653-654
[25] WANG HC, CHENG KI, CHEN PR, et al. Glycine receptors expression in rat spinal cord and dorsal root ganglion in prostaglandin E2 intrathecal injection models. BMC Neurosci. 2018;19(1):72.
[26] KIM TK, PARK D, BAN YH, et al. Improvement by Human Oligodendrocyte Progenitor Cells of Neurobehavioral Disorders in an Experimental Model of Neonatal Periventricular Leukomalacia. Cell Transplant. 2018;27(7):1168-1177.
[27] FAN LW, CARTER K, BHATT A, et al. Rapid transport of insulin to the brain following intranasal administration in rats. Neural Regen Res. 2019;14(6):1046-1051.
[28] SHAHROR RA, WU CC, CHIANG YH, et al. Tracking Superparamagnetic Iron Oxide-labeled Mesenchymal Stem Cells using MRI after Intranasal Delivery in a Traumatic Brain Injury Murine Model. J Vis Exp. 2019; (153): 60450.
[29] MCDONALD CA, DJULIANNISAA Z, PETRAKI M, et al. Intranasal Delivery of Mesenchymal Stromal Cells Protects against Neonatal Hypoxic⁻Ischemic Brain Injury. Int J Mol Sci. 2019;20(10). pii: E2449.
[30] CHAU MJ, DEVEAU TC, GU X, et al. Delayed and repeated intranasal delivery of bone marrow stromal cells increases regeneration and functional recovery after ischemic stroke in mice. BMC Neurosci. 2018; 19(1):20.
[31] NIJBOER CH, KOOIJMAN E, VAN VELTHOVEN CT, et al. Intranasal Stem Cell Treatment as a Novel Therapy for Subarachnoid Hemorrhage. Stem Cells Dev. 2018;27(5):313-325.
[32] LYONS FG, MATTEI TA. Sources, Identification, and Clinical Implications of Heterogeneity in Human Umbilical Cord Stem Cells. Adv Exp Med Biol. 2019;1169:243-256.
[33] MARINO L, CASTALDI MA, ROSAMILIO R, et al. Mesenchymal Stem Cells from the Wharton’s Jelly of the Human Umbilical Cord: Biological Properties and Therapeutic Potential. Int J Stem Cells. 2019;12(2): 218-226.
[34] ZHAO Q, HU J, XIANG J, et al. Intranasal administration of human umbilical cord mesenchymal stem cells-conditioned medium enhances vascular remodeling after stroke. Brain Res. 2015;1624:489-496.
[35] LI J, YAWNO T, SUTHERLAND AE, et al. Preterm umbilical cord blood derived mesenchymal stem/stromal cells protect preterm white matter brain development against hypoxia-ischemia. Exp Neurol. 2018; 308:120-131.
[36] KORSHUNOVA I, RHEIN S, GARCÍA-GONZÁLEZ D, et al. Genetic modification increases the survival and the neuroregenerative properties of transplanted neural stem cells. JCI Insight. 2020;5(4). pii: 126268.
[37] ZHENG ZC, CHEN YX, DU XJ, et al.Neural stem cell transplantation inhibits glial cell proliferation and P2X receptor-mediated neuropathic pain in spinal cord injury rats. Neural Regen Res. 2019;14(5):876-885.
[38] HAYASHI Y, LIN HT, LEE CC, et al. Effects of neural stem cell transplantation in Alzheimer’s disease models. J Biomed Sci. 2020; 27(1):29.
[39] SHUAIB A, MURABIT MA, KANTHAN R, et al. The neuroprotective effects of gamma-vinyl GABA in transient global ischemia: a morphological study with early and delayed evaluations. Neurosci Lett. 1996; 204 (1-2):1-4.
[40] CLOWRY GJ, BASUODAN R, CHAN F. What are the Best Animal models for testing early intervention in cerebral palsy? Front Neurol. 2014;5:258.
[41] DANIELYAN L, SCHÄFER R, VON AMELN-MAYERHOFER A, et al. Intranasal delivery of cells to the brain. Eur J Cell Biol. 2009;88(6): 315-324.
[42] MORETTI R, PANSIOT J, BETTATI D, et al. Blood-brain barrier dysfunction in disorders of the developing brain. Front Neurosci. 2015;9:40.
[43] HAGBERG H, MALLARD C, FERRIERO DM, et al. The role of inflammation in perinatal brain injury. Nat Rev Neurol. 2015;11(4):192-208.
[44] THOMI G, SURBEK D, HAESLER V, et al. Exosomes derived from umbilical cord mesenchymal stem cells reduce microglia-mediated neuroinflammation in perinatal brain injury. Stem Cell Res Ther. 2019; 10(1):105.
[45] LIU S, YUAN M, HOU K, et al. Immune characterization of mesenchymal stem cells in human umbilical cord Wharton’s jelly and derived cartilage cells. Cell Immunol. 2012;278(1-2):35-44.
[46] HOVAKIMYAN M, MÜLLER J, WREE A, et al. Survival of transplanted human neural stem cell line (ReNcell VM) into the rat brain with and without immunosuppression. Ann Anat. 2012;194(5):429-435.
[47] KEEP M, ELMÉR E, FONG KS, et al. Intrathecal cyclosporin prolongs survival of late-stage ALS mice. Brain Res. 2001;894(2):327-331.
[48] FRIBERG H, WIELOCH T. Mitochondrial permeability transition in acute neurodegeneration. Biochimie. 2002;84(2-3):241-250.
[49] SINIGAGLIA-COIMBRA R, CAVALHEIRO EA, COIMBRA C. Protective effect of systemic treatment with cyclosporine A after global ischemia in rats. J Neurol Sci. 2002;203-204:273-276.
[50] COOL SK, BREYNE K, MEYER E, et al. Comparison of in vivo optical systems for bioluminescence and fluorescence imaging. J Fluoresc. 2013;23(5):909-920.