Stem cells for neonatal hypoxic-ischemic injury

Home/2013, Vol. 1, No. 1/Stem cells for neonatal hypoxic-ischemic injury

Cell and Organ Transplantology. 2013, 1(1): 10-13.
DOI: 10.22494/COT.V1I1.44  

Stem cells for neonatal hypoxic-ischemic injury

Carroll James
Georgia Health Sciences University, Augusta, GА, USA

Many types of adult stem cells have been used in pre-clinical situations to treat experimental hypoxic-ischemic (HI) injury in neonatal animals. Numerous laboratory reports have appeared in the literature indicating that this treatment is beneficial, and the route of cell administration does not appear to be critical. The success of treatment occurs with administration soon after the injury, and this early administration of the cells proximate to the time of injury appears to be decisive. The mechanism of benefit relates to preservation of intrinsic neurons at the site of injury rather than cell replacement by the administered cells. There are few clinical studies, and most positive reports are either from uncontrolled studies or anecdotal. Given the preclinical success with treatment, well-thought-out clinical studies need to be initiated in acutely brain injured neonates.

Full Text PDF (eng) Full text PDF (ua)


1. Carroll J, Borlongan C. Adult Stem Cell Therapy for Acute Brain Injury in Children. CNS & Neurological Disorders Drug Targets. 2008; 7:1-8.
2. Keene C, Ortiz-Gonzalez X, Jiang Y, et al. Neural differentiation and incorporation of bone marrow-derived multipotent adult progenitor cells after single cell transplantation into blastocyst stage mouse embryos. Cell Transplant. 2003; 12(3):201-13.
3. Yamagata M, Yamamoto A, Kako E, et al. Human dental pulp-derived stem cells protect against hypoxic-ischemic injury in neonatal mice. Stroke. 2013; 44(2):551-554.
4. Lee I, Jung K, Kim M et al. Neural stem cells: properties and therapeutic potentials for hypoxic-ischemic brain injury in newborn infants. Pediatrics International. 2010; 52(6):855-65.
5. Takahashi K, Yamanaka S. Induced pluripotent stem cells in medicine and biology. Development. 2013; 140(12):2257-67.
6. Bartley J, Soltau T, Wimbourne H, et al. BrdU-positive cells in the neonatal mouse hippocampus following hypoxic-ischemic brain injury. BMC Neuroscience. 2005; 6:15.
PMid:15743533 PMCid:PMC555560
7. Donega V, van Velthoven CT, Nijboer CH, et al. The endogenous regenerative capacity of the damaged newborn brain: neurogenesis with mesenchymal stem cell treatment. J Cerebral Blood Flow & Metabolism. 2013; 33(5):625-34.
PMid:23403379 PMCid:PMC3652688
8. Rice J, Vannucci R, Brierly J. The influence of immaturity on hypoxic-ischemic brain damage in the rat. Ann Neurol. 1981; 9(2):131-41.
9. Donega V, van Velthoven C, Nijboer C, et al. Intranasal mesenchymal stem cell treatment for neonatal brain damage: long-term cognitive and sensorimotor improvement. PLoS ONE. 2013; 8(1):51253.
PMid:23300948 PMCid:PMC3536775
10. Rosenblum S, Wang N, Smith T, et al. Timing of intra-arterial neural stem cell transplantation after hypoxia-ischemia influences cell engraftment, survival, and differentiation. Stroke. 2012; 43(6):1624-31.
11. Park S, Koh SE, Maeng S, et al. Neural progenitors generated from mesenchymal stem cells of first-trimester human placenta matured in the hypoxic-ischemic rat brain and mediated restoration of locomotor activity. Placenta. 2011; 32(3):269-76.
12. Lee J, Kim B, Jo C, et al. Mesenchymal stem-cell transplantation for hypoxic-ischemic brain injury in neonatal rat model. Pediatric research. 2010; 67(1):42-6.
13. de Paula S, Greggio S, Marinowic D, et al. The dose-response effect of acute intravenous umbilical cord blood cells on brain damage and neonatal hypoxia-ischemia. Neuroscience. 2012; 210:431-41.
14. Kim ES, Ahn SY, Im GH et al. Human umbilical cord blood-derived mesenchymal stem cell transplantation attenuates severe brain injury by permanent middle cerebral artery occlusion in newborn rats. Pediatr Res. 2012, 72(3):277-84.
15. Meier C, Middelanis J, Wasielewski B, et al. Spastic paresis after perinatal brain damage in rats is reduced by human cord blood mononuclear cells. Pediatric Research. 2006; 59(2):244-49.
16. Yasuhara T, Matsukawa N, Yu G, et al. Transplantation of cryopreserved human bone marrow-derived multipotent adult progenitor cells of neonatal hypoxic-ischemic injury: targeting the hippocampus. Reviews in the Neurosciences. 2006; 17(1-2):215-25.
17. Yasuhara T, Hara K, Maki M, et al. Intravenous grafts recapitulate the neurorestoration afforded by intracerebrally delivered multipotent adult progenitor cells in neonatal hypoxic-ischemic rats. J Cerebral Blood Flow and Metabolism. 2008; 28:1804-10.
PMid:18594556 PMCid:PMC2587070
18. van Velthoven C, Kavelaars A, van Bel F, Heijnen C. Nasal administration of stem cells: a promising novel route for ischemic brain damage. Pediatric Research. 2010; 68(5):419-22.
19. Carroll J. Human cord blood for the hypoxic-ischemic neonate. Pediatr Res. 2012; 71(4 Pt 2):459-63.
PMid:22278181 PMCid:PMC3640287
20. Van Velthoven C, Kavelaars A, Heijnen C. Mesenchymal stem cells as a treatment for neonatal ischemia. Pediatr Res. 2012; 71(4 Pt 2):474-81.
21. Erices A, Conget P, Minguell J. Mesenchymal progenitor cell in human umbilical cord blood. British Journal of Haematology. 2000; 109(1):235-42.
22. Zhao L, Duan W, Reyes M, et al. Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats. Experimental Neurology. 2002; 174(1):11-20.
23. van Velthoven C, Kavalaars A, van Bel F, et al. Mesenchymal stem cell transplantation changes the gene expression of the neonatal ischemic brain. Brain, Behavior & Immunity. 2011; 25(7):1342-48.
24. Daadi M, Davis A, Arac A, et al. Human neural stem cell grafts modify microglial response and enhance axonal sprouting in neonatal hypoxic-ischemic brain injury. Stroke. 2010; 41(3):516-23.
25. Wasielewski B, Jensen A, Roth-Harer A, et al. Neuroglial activation and CX43 expression are reduced upon transplantation of human umbilical cord blood cells after perinatal hypoxic-ischemic injury. Brain Res. 2012; 1487:39-53.
26. Borlongan C, Lind J, Dillon-Carter O, et al. Bone marrow grafts restore cerebral blood flow and blood brain barrier in stroke rats. Brain Res. 2004; 1010(1-2):108-16.
27. Robinson S, Niu T, de Lima M, et al. Ex vivo expansion of umbilical cord blood. Cytotherapy. 2005; 7(3):243-50.
28. van Velthoven C, van de Lootj Y, Kavalaars A, et al. Mesenchymal stem cells restore cortical rewiring after neonatal ischemia in mice. Annals of Neurology. 2012; 71(6):785-96.
29. Luan Z, Liu W, Qu S, et al. Treatment of newborns with severe injured brain with transplantation of human neural precursor cells. Zhonghua Erke Zazhi. 2011; 49(6):445-49.
30. Luan Z, Yin G, Hu X, et al. Treatment of an infant with severe neonatal hypoxic-ischemic encephalopathy sequelae with transplantation of human neural stem cells into cerebral ventricle. Zhonghua Erke Zazhi. 2005; 43(8):580-83.

Carroll J. Stem cells for neonatal hypoxic-ischemic injury. Cell and Organ Transplantology. 2013; 1(1):10-13. doi: 10.22494/COT.V1I1.44


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