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

Adam D. Bachstetter; Mibel M. Pabon; Michael J. Cole; Charles E. Hudson; Paul R. Sanberg; Alison E. Willing; Paula C. Bickford; Carmelina Gemma

doi:10.1186/1471-2202-9-22

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

Adam D. Bachstetter
, Mibel M. Pabon
, Michael J. Cole
, Charles E. Hudson
, Paul R. Sanberg
, Alison E. Willing
, Paula C. Bickford
, Carmelina Gemma

Research output: Contribution to journal › Article › peer-review

92 Scopus citations

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.

Original language	English
Pages (from-to)	22
Number of pages	1
Journal	BMC Neuroscience
Volume	9
DOIs	https://doi.org/10.1186/1471-2202-9-22
State	Published - Feb 14 2008

Bibliographical note

Funding Information:
This work was supported by: NIH grant R21AG024165 (CG), PO1AG04418 (PCB), and R01AG020927(AEW); The US Veterans Administration Medical Research Service; In part by, the Analytic Microscopy Core Facility at the H. Lee Moffitt Cancer Center and Research Institute. The UCBMC were generously donated by Saneron CCEL Therapeutics Inc. Thanks are due to Ning Chen, and Craig T. Ajmo Jr., for their technical assistance.

Funding

This work was supported by: NIH grant R21AG024165 (CG), PO1AG04418 (PCB), and R01AG020927(AEW); The US Veterans Administration Medical Research Service; In part by, the Analytic Microscopy Core Facility at the H. Lee Moffitt Cancer Center and Research Institute. The UCBMC were generously donated by Saneron CCEL Therapeutics Inc. Thanks are due to Ning Chen, and Craig T. Ajmo Jr., for their technical assistance.

Funders	Funder number
US Veterans Administration Medical Research Service
National Institutes of Health (NIH)	PO1AG04418, R01AG020927
National Institute on Aging	R21AG024165

ASJC Scopus subject areas

General Neuroscience
Cellular and Molecular Neuroscience

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10.1186/1471-2202-9-22

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title = "Peripheral injection of human umbilical cord blood stimulates neurogenesis in the aged rat brain",

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.",

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note = "Funding Information: This work was supported by: NIH grant R21AG024165 (CG), PO1AG04418 (PCB), and R01AG020927(AEW); The US Veterans Administration Medical Research Service; In part by, the Analytic Microscopy Core Facility at the H. Lee Moffitt Cancer Center and Research Institute. The UCBMC were generously donated by Saneron CCEL Therapeutics Inc. Thanks are due to Ning Chen, and Craig T. Ajmo Jr., for their technical assistance.",

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AU - Sanberg, Paul R.

AU - Willing, Alison E.

AU - Bickford, Paula C.

AU - Gemma, Carmelina

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PY - 2008/2/14

Y1 - 2008/2/14

N2 - 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.

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

Abstract

Bibliographical note

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ASJC Scopus subject areas

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