Third trimester NG2-positive amniotic fluid cells are effective in improving repair in spinal cord injury.
Spinal cord injury presents a significant therapeutic challenge since the treatments available are mostly vain. The use of stem cells to treat this condition represents a promising new therapeutic strategy; therefore, a variety of stem cell treatments have been recently examined in animal models of CNS trauma. In this work, we analyzed the effects of third trimester amniotic fluid cells in a mouse model of spinal cord injury. Among the different cultures used for transplantation, some were able to induce a significant improvement in motor recovery (cultures #3.5, #3.6 and #7.30), evaluated by means of open field free locomotion. All effective cell cultures expressed the surface marker nerve/glial antigen 2, ortholog of the human chondroitin sulfate proteoglycan 4, which is present on several types of immature progenitor cells. The improved motor functional recovery was correlated with higher myelin preservation in the ventral horn white matter and an increased vascularization in the peri-lesion area. Real-Time PCR analysis showed higher expression levels of vascular endothelial growth factor and hypoxia-inducible factor-1α mRNA two days after cells transplantation compared to PBS-treated animals, indicating that an angiogenic pathway might have been activated by these cells, possibly through the production of hepatocyte growth factor. This cytokine appears to be produced mostly in filtering organs, such as the lung, of the transplanted animals and is likely released in the blood suggesting an endocrine role of hepatocyte growth factor in targeting the injury site.
Department of Health Science, Faculty of Medicine, University of Milan, Via A. di Rudinì 8, 20142 Milan, Italy. Electronic address: daniele.bottai@unimi.it.
Daniele
D
Bottai
Department of Health Science, Faculty of Medicine, University of Milan, Via A. di Rudinì 8, 20142 Milan, Italy.
Giuseppe
G
Scesa
Department of Health Science, Faculty of Medicine, University of Milan, Via A. di Rudinì 8, 20142 Milan, Italy.
Daniela
D
Cigognini
Department of Health Science, Faculty of Medicine, University of Milan, Via A. di Rudinì 8, 20142 Milan, Italy.
Raffaella
R
Adami
Department of Health Science, Faculty of Medicine, University of Milan, Via A. di Rudinì 8, 20142 Milan, Italy.
Emanuela
E
Nicora
Istituto Nazionale di Genetica Molecolare-INGM, Via Francesco Sforza, 28, 20122 Milan, Italy.
Sergio
S
Abrignani
Department of Health Science, Faculty of Medicine, University of Milan, Via A. di Rudinì 8, 20142 Milan, Italy.
Anna Maria
AM
Di Giulio
Department of Health Science, Faculty of Medicine, University of Milan, Via A. di Rudinì 8, 20142 Milan, Italy. Electronic address: alfredo.gorio@unimi.it.
Alfredo
A
Gorio
D000653:Amniotic Fluid / Q000166:cytology*; D042501:Angiogenic Proteins / Q000235:genetics; D000818:Animals; D000941:Antigens / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D017228:Hepatocyte Growth Factor / Q000097:blood / Q000235:genetics; D006801:Humans; D008168:Lung / Q000166:cytology; D008297:Male; D051379:Mice; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D011509:Proteoglycans / Q000378:metabolism; D020127:Recovery of Function / Q000502:physiology; D013116:Spinal Cord / Q000098:blood supply / Q000473:pathology*; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000379:methods*; D016896:Treatment Outcome; D000099216:Chondroitin Sulfate Proteoglycan 4
D042501:Angiogenic Proteins; D000941:Antigens; D015415:Biomarkers; D017228:Hepatocyte Growth Factor; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4
Amniotic fluid cells; Angiogenesis; HGF; NG2; Spinal cord injury