Autologous Cord Blood in Children with Cerebral Palsy: A Review
Abstract
:1. Introduction
2. The Scientific Basis for the Use of Umbilical Cord Blood in the Treatment of Cerebral Palsy
2.1. Cord Blood Composition and Its Mode of Action
2.1.1. Homing and Neurodifferentiation
2.1.2. Extracellular Vesicles
2.1.3. Tunnelling
2.2. Efficacy of MSC Administration in Animal Models of Hypoxia
2.3. The Influence of Low Oxygen Concentration on Stem Cells
3. Clinical Trials Assessing the Use of Autologous Umbilical Cord Blood in the Treatment of Cerebral Palsy
3.1. Early Phase Clinical Studies
3.2. Safety
4. Past and Future Perspectives
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
BDNF | brain-derived neutrophic factor |
BM | bone marrow |
CB | cord blood |
CNS | central nervous system |
CP | cerebral palsy |
EEG | Electroencephalography |
EPC | endothelial progenitor cells |
EV | extracellular vesicles |
GCSF | granulocyte colony stimulating factor |
GMFM-88 | Gross Motor Function Measure |
HIE | hypoxic-ischemic encephalopathy |
HLA | human leukocyte antigen |
hUCB | human umbilical cord blood |
MDSC | monocyte-derived suppressor cells |
MRI | magnetic resonance imaging |
MSC | mesenchymal stem cell |
OR | odds ratio |
TNC | total nucleated cells |
Treg | regulatory T cells |
TrkB | tropomyosin receptor kinase B |
UC | umbilical cord |
UCB | umbilical cord blood |
WJ | Wharton’s jelly |
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Cell Targets | Effect | |
---|---|---|
BDNF | tTrkB, LNGFR [43], alpha-7 nicotinic receptor [44], reelin [45] | ↑ proliferation and differentiation of oligodendrocyte precursor cells [34] ↑ myelination [34] |
EGF | JAK/STAT, MAPK, Pi3K/Akt [37] | ↑ survival, proliferation, and migration of neural precursor cells [37] ↑ differentiation towards oligodendrocyte [37] |
↑ proliferation of astrocytes [37] | ||
GCSF | JAK/STAT, MAPK, PI3K/Akt [36] | ↑ neurogenesis [46] ↓ apoptosis [46] |
GDNF | STAT3 [47] | ↑ differentiation of neural precursor cells into astrocytes [47,48] ↓ apoptosis [48] |
IGF-1 | ERK, Pi3K/Akt [40] | ↑ neural stem cell proliferation and migration [42] |
Disease | Effect |
---|---|
Stroke [59] | ↑ synaptogenesis, ↑ angiogenesis |
Traumatic brain injury [58] | ↓ apoptosis |
Inflammation-induced preterm brain injury [57] | ↓ inflammation-induced neuronal degeneration, ↓ microgliosis, ↓ astrogliosis |
Parkinson’s disease [60] | ↓ apoptosis |
Alzheimer’s disease [61] | neprilysin secretion |
Autism [62] | ↓ autistic behaviors |
Hepatic ischemia [50] | ↓ necrosis, ↓ apoptosis, ↓ inflammation, ↓ oxidative stress |
Hepatic failure [51] | ↓ apoptosis, ↓ inflammation |
Hepatocellular carcinoma [52] | ↓ tumor |
Myocardial infarction [53] | ↑ neovascularization, ↓ inflammation |
Myocardial hypoxia [54] | ↑ Wnt/β-catenin signaling pathway (↑ survival, ↓ apoptosis) |
Ischemic-hypoxic kidney injury [55,56] | ↓ apoptosis, ↓ inflammation, ↑ proliferation, ↑ function, ↓ CX3CL1, ↓ CD68+ |
ClinicalTrials.gov ID | Therapy | Sample Size (n) | Phase | Status on 18 January 2019 |
---|---|---|---|---|
NCT02881970 | Autologous cord blood | 20 | I, II | Not yet recruiting |
NCT02551003 | Autologous cord blood + hypothermia | 60 | I, II | Recruiting |
NCT03352310 | Autologous cord blood | 40 | I | Recruiting |
NCT02434965 | Autologous cord blood and human placenta-derived stem cells | 20 | II | Not yet recruiting |
NCT02612155 | Autologous cord blood | 160 | II | Recruiting |
NCT03123081 | Umbilical cord milking | 400 | NS | Not yet recruiting |
NCT03682042 | Umbilical cord milking | 350 | NS | Not yet recruiting |
NCT03657394 | Umbilical cord milking | 1400 | III | Not yet recruiting |
NCT01072370 | Autologous cord blood | 40 | I, II | Recruiting |
NCT03791372 | Autologous umbilical cord blood mononuclear cells | 25 | I | Recruiting |
NCT03327467 | Autologous or sibling cord blood | NS | NS | Available |
Parameter | Effect | Model |
---|---|---|
Proliferation | Increased | Rat BM-MSC cultures [135] Mice BM-MSC cultures [130] |
Viability | Increased | Human BM cell cultures [134] |
Decreased | hPSCs [140], hHSC, and progenitors [137], human embryonic NSCs culture [138] | |
Migration | Increased | Human embryonic NSCs culture [138] |
Resistance to oxidative stress | Increased | Human BM cell cultures [134] |
Differentiation | ||
into neural cells | Increased | Human embryonic NSCs culture [138] |
into bone cells | Increased | Rat BM-MSCs cultures [129], mice BM-MSC cultures [130] |
Decreased | Human BM cell cultures [133] | |
into β-cells | Increased | Rat BM-MSCs cultures [131] |
into hepatic cells | Increased | Human BM cell cultures [134] |
into fat tissue cells | Increased | Human BM cell cultures [133] |
Proinflammatory cytokines | Decreased | Rat model of spinal cord injury [132] |
Anti-inflammatory cytokines | Increased | Rat model of spinal cord injury [132] |
Angiogenic factor secretion | Increased | Rat BM-MSC cultures [135] |
BDNF secretion | Increased | Human embryonic NSCs culture [138] |
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Boruczkowski, D.; Pujal, J.-M.; Zdolińska-Malinowska, I. Autologous Cord Blood in Children with Cerebral Palsy: A Review. Int. J. Mol. Sci. 2019, 20, 2433. https://doi.org/10.3390/ijms20102433
Boruczkowski D, Pujal J-M, Zdolińska-Malinowska I. Autologous Cord Blood in Children with Cerebral Palsy: A Review. International Journal of Molecular Sciences. 2019; 20(10):2433. https://doi.org/10.3390/ijms20102433
Chicago/Turabian StyleBoruczkowski, Dariusz, Josep-Maria Pujal, and Izabela Zdolińska-Malinowska. 2019. "Autologous Cord Blood in Children with Cerebral Palsy: A Review" International Journal of Molecular Sciences 20, no. 10: 2433. https://doi.org/10.3390/ijms20102433