Pretreated monocytes may confer positive effects for Alzheimer’s sufferers

Cell transplantation research using animals modelled with Alzheimer’s disease has indicated that human umbilical cord blood cells (HUCBCs) can ameliorate some cognitive deficits and reduce the effects of the amyloid-beta (Aβ) plaques, one of the physiological hallmarks of the disease.

However, the role that HUCBCs play in Aβ clearance has yet to be elucidated.

Monocytes are peripheral blood mononuclear cells (MNCs) with round nuclei that are critical components in the immune system for fighting infection and processing foreign material. A team of American, Chinese, and Japanese researchers hypothesized that monocytes derived from cord blood can help clear aggregated Aβ protein when transplanted into laboratory animals modelled with Alzheimer’s disease.

“We previously reported that HUCBCs modulated inflammation, diminished Aβ pathology, and reduced behavioural deficits in mice modelled with Alzheimer’s disease,” said Dr Donna Darlington of the Rashid Laboratory for Developmental Neurobiology at the Silver Child Development Centre, University of South Florida. “In this study, we attempted to determine which MNC population was conferring these effects and to determine the mechanism by which these effects occur.”

HUCBC-derived monocytes improved hippocampal-dependent learning, memory and motor function

Over a period of two to four months, the researchers treated Alzheimer’s disease modelled mice with HUCBC-derived monocytes followed by behavioural evaluation and biochemical and histological analyses.

The researchers found that administration of HUCBC-derived monocytes not only diminished Aβ pathology in the test mice, but also improved hippocampal-dependent learning, memory, and motor function.

“MNCs may exert a therapeutic effect through phagocytosis of dead cells and cellular debris. We believe that phagocytosis (a process by which cells internalize solid particles) is a possible mechanism by which MNCs mediate Aβ clearance,” said the researchers. “Most importantly, we found that aged monocytes were less effective against Aβ and that soluble amyloid precursor protein (sAPPa) could restore the phagocytic capabilities of these endogenous aged cells.”

“This study contributes insight into the possible mechanisms by which monocytes exert therapeutic effects,” said Dr Shinn-Zong Lin, Vice Superintendent for the Centre of Neuropsychiatry, Professor of Neurosurgery at China Medical University Hospital. “Future studies should weigh the benefits of using MNCs in cell therapy versus the possible detrimental effects, such as secretion of neurotoxic, inflammatory factors. The effectiveness of using MNCs in human Alzheimer’s disease patients should also be validated, as it has been a matter of conjecture.”

The study will be published in a future issue of Cell Transplantation and is currently freely available on-line as an unedited version.