Umbilical Cord Cell Therapy Improves Spatial Memory in Aging Rats
There is a growing interest in the potential of adult stem cells for implementing regenerative medicine in the brain. We assessed the effect of intracerebroventricular (icv) administration of human umbilical cord perivascular cells (HUCPVCs) on spatial memory of senile (27 mo) female rats, using intact senile counterparts as controls. Approximately one third of the animals were injected in the lateral ventricles with a suspension containing 4.8 X 105 HUCPVC in 8 μl per side. The other third received 4.8 X 105 transgenic HUCPVC overexpressing Insulin-like growth factor-1 (IGF-1) and the last third of the rats received no treatment. Spatial memory performance was evaluated using a modified version of the Barnes maze test. In order to evaluate learning ability as well as spatial memory retention, we assessed the time spent (permanence) by animals in goal sector 1 (GS1) and 3 (GS3) when the escape box was removed. Fluorescence microscopy revealed the prescence of Dil-labeled HUCPVC in coronal sections of treated brains. The HUCPVC were located in close contact with the ependymal cells with only a few labeled cells migrating into the brain parenchyma. After treatment with naïve or IGF-1 transgenic HUCPVC, permanence in GS1 and GS3 increased significantly whereas there were no changes in the intact animals. We conclude that HUCPVC injected icv are effective to improve some components of spatial memory in senile rats. The ready accessibility of HUCPVC constitutes a significant incentive to continue the exploration of their therapeutic potential on neurodegenerative diseases.
KeywordsBrain aging Spatial memory Hippocampus Umbilical cord Stem cells
The authors are indebted to Ms. Natalia Scelsio for technical work, to Mr. Mario R. Ramos for design of the figures and to Ms. Yolanda E. Sosa for editorial assistance. MGG, GM, GRM, PCR and RGG are career researchers of the Argentine Research Council (CONICET). ML, FZ and MCM are recipients of CONICET doctoral fellowships.
This study was supported by grant #PICT15–0817 from the Argentine Agency for the Promotion of Science and Technology and grant MRCF 10–10-17 from the Medical Research Charitable Foundation and the Society for Experimental Gerontological Research, New Zealand to RGG.
Compliance with Ethical Standards
Conflict of Interest
There are no conflicts of interest concerning any of the authors.
- 7.Bayo J., Fiore, E, Aquino, J B, et al. (2014) Human umbilical cord perivascular cells exhibited enhanced migration capacity towards hepatocellular carcinoma in comparison with bone marrow mesenchymal stromal cells: A role for autocrine motility factor receptor. Biomed. Res. Int. https://doi.org/10.1155/2014/837420.
- 8.Paxinos, G., & Watson, C. (1998). The rat brain in stereotaxic coordinates (4th ed.). San Diego: Academic Press.Google Scholar
- 11.The Safety and The Efficacy Evaluation of NEUROSTEM®-AD in Patients With Alzheimer’s Disease. ClinicalTrialsgov Identifier: NCT01297218. 2014. http://clinicaltrials.gov/ct2/show/ NCT01297218.
- 12.Safety and efficiency of umbilical cord-derived mesenchymal stem cells (UC-MSC) in patients with Alzheimer’s disease (SEMAD). Clinical Trialsgov Identifier: NCT01547689. May. 2014 https://clinicaltrials.gov/ct2/show/NCT01547689
- 13.Safety and exploratory efficacy study of NEUROSTEM® versus placebo in patients with Alzheimer’s disease. Clinicaltrialsgov identifier: nct02054208. Feb. 2014 https://clinicaltrials.gov/ct2/show/NCT02054208