Peripheral injection of human umbilical cord blood stimulates neurogenesis in the aged rat brain

Adam D Bachstetter¹^,2 , Mibel M Pabon¹^,2 , Michael J Cole² , Charles E Hudson³ , Paul R Sanberg¹^,2^,4 , Alison E Willing¹^,2 , Paula C Bickford¹^,2^,3 and Carmelina Gemma¹^,2^,3

¹Department of Molecular Pharmacology and Physiology, University of South Florida, College of Medicine, Tampa, FL 33612, USA

²Department of Neurosurgery, Center of Excellence for Aging and Brain Repair, University of South Florida, College of Medicine, Tampa, FL 33612, USA

³James A. Haley Veterans Administration Hospital, Tampa, FL 33612, USA

⁴Saneron CCEL Therapeutics Inc., Temple Terrace, FL 33617, USA

author email corresponding author email

BMC Neuroscience 2008, 9:22doi:10.1186/1471-2202-9-22


Published:	14 February 2008

Abstract

Background

Neurogenesis continues to occur throughout life but dramatically decreases with increasing age. This decrease is mostly related to a decline in proliferative activity as a result of an impoverishment of the microenvironment of the aged brain, including a reduction in trophic factors and increased inflammation.

Results

We determined that human umbilical cord blood mononuclear cells (UCBMC) given peripherally, by an intravenous injection, could rejuvenate the proliferative activity of the aged neural stem/progenitor cells. This increase in proliferation lasted for at least 15 days after the delivery of the UCBMC. Along with the increase in proliferation following UCBMC treatment, an increase in neurogenesis was also found in the aged animals. The increase in neurogenesis as a result of UCBMC treatment seemed to be due to a decrease in inflammation, as a decrease in the number of activated microglia was found and this decrease correlated with the increase in neurogenesis.

Conclusion

The results demonstrate that a single intravenous injection of UCBMC in aged rats can significantly improve the microenvironment of the aged hippocampus and rejuvenate the aged neural stem/progenitor cells. Our results raise the possibility of a peripherally administered cell therapy as an effective approach to improve the microenvironment of the aged brain.