Intracerebroventricular Transplantation of Cord Blood-Derived Neural Progenitors in a Child with Severe Global Brain Ischemic Injury

Cell Medicine

Mieczyslaw Litwin¹  Sergiusz Jozwiak²  Katarzyna Kotulska²  Tomasz Kmiec²  Elzbieta Jurkiewicz³  Jerzy Walecki⁴  Miroslaw Janowski⁵  Barbara Lukomska⁵  Aleksandra Habich⁵  Anna Sarnowska⁵  Krystyna Domanska-Janik⁵  Marcin Roszkowski⁶  Tomasz Kropiwnicki⁶  Tomasz Oldak⁷  Dariusz Boruczkowski⁷ 

[1] #Department of Nephrology, The Children's Memorial Health Institute, Warsaw, Poland;*Department of Neurology and Epileptology, The Children's Memorial Health Institute, Warsaw, Poland;§Department of Radiology, MR Unit, The Children's Memorial Health Institute, Warsaw, Poland;¶Department of Radiology and Diagnostic Imaging, Postgraduate Medical Centre and Experimental Pharmacology Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland;†NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland;‡Department of Neurosurgery, The Children's Memorial Health Institute, Warsaw, Poland;∗∗Polish Stem Cell Bank, Warsaw, Poland

关键词: Cord blood;    Neural progenitors;    Clinical transplantation;    Brain ischemia;   

DOI  :  10.3727/215517910X536618

学科分类：生物科学（综合）

来源: Cognizant Communication Corporation

【 摘 要 】

Transplantation of neural stem/precursor cells has recently been proposed as a promising, albeit still controversial, approach to brain repair. Human umbilical cord blood could be a source of such therapeutic cells, proven beneficial in several preclinical models of stroke. Intracerebroventricular infusion of neutrally committed cord blood-derived cells allows their broad distribution in the CNS, whereas additional labeling with iron oxide nanoparticles (SPIO) enables to follow the fate of engrafted cells by MRI. A 16-month-old child at 7 months after the onset of cardiac arrest-induced global hypoxic/ischemic brain injury, resulting in a permanent vegetative state, was subjected to intracerebroventricular transplantation of the autologous neutrally committed cord blood cells. These cells obtained by 10-day culture in vitro in neurogenic conditions were tagged with SPIO nanoparticles and grafted monthly by three serial injections (12 × 106 cells/0.5 ml) into lateral ventricle of the brain. Neural conversion of cord blood cells and superparamagnetic labeling efficiency was confirmed by gene expression, immunocytochemistry, and phantom study. MRI examination revealed the discrete hypointense areas appearing immediately after transplantation in the vicinity of lateral ventricles wall with subsequent lowering of the signal during entire period of observation. The child was followed up for 6 months after the last transplantation and his neurological status slightly but significantly improved. No clinically significant adverse events were noted. This report indicates that intracerebroventricular transplantation of autologous, neutrally committed cord blood cells is a feasible, well tolerated, and safe procedure, at least during 6 months of our observation period. Moreover, a cell-related MRI signal persisted at a wall of lateral ventricle for more than 4 months and could be monitored in transplanted brain hemisphere.

【 授权许可】

CC BY