Intracerebral Transplantation of Adipose-Derived Mesenchymal Stem Cells Alternatively Activates Microglia and Ameliorates Neuropathological Deficits in Alzheimer's Disease Mice

Abstract

Recent studies suggest that transplantation of mesenchymal stem cells might have therapeutic effects in preventing pathogenesis of several neurodegenerative disorders. Adipose-derived mesenchymal stem cells (ADSCs) are a promising new cell source for regenerative therapy. However, whether transplantation of ADSCs could actually ameliorate the neuropathological deficits in Alzheimer's disease (AD) and the mechanisms involved has not yet been established. Here, we evaluated the therapeutic effects of intracerebral ADSC transplantation on AD pathology and spatial learning/memory of APP/PS1 double transgenic AD model mice. Results showed that ADSC transplantation dramatically reduced b-amyloid (Ab) peptide deposition and significantly restored the learning/memory function in APP/PS1 transgenic mice. It was observed that in both regions of the hippocampus and the cortex there were more activated microglia, which preferentially surrounded and infiltrated into plaques after ADSC transplantation. The activated microglia exhibited an alternatively activated phenotype, as indicated by their decreased expression levels of proinflammatory factors and elevated expression levels of alternative activation markers, as well as Ab-degrading enzymes. In conclusion, ADSC transplantation could modulate microglial activation in AD mice, mitigate AD symptoms, and alleviate cognitive decline, all of which suggest ADSC transplantation as a promising choice for AD therapy. This manuscript is published as part of the International Association of Neurorestoratology (IANR) supplement issue of Cell Transplantation.

Therapeutic Potential of Human Adipose-Derived Stem Cells in Neurological Disorders

“…These studies suggested that activated microglia might be involved in the mechanisms to ameliorate the neuropathological deficits in AD (20,21). More activated microglia were detected in both regions of the hippocampus and cortex after ASCs transplantation, exhibiting decreased expression levels of pro-inflammatory factors and elevated expression levels of Ab-degrading enzymes as well as neprilysin (20,21).…”

“…More activated microglia were detected in both regions of the hippocampus and cortex after ASCs transplantation, exhibiting decreased expression levels of pro-inflammatory factors and elevated expression levels of Ab-degrading enzymes as well as neprilysin (20,21). The mechanisms behind the role of ASC in microglial activation are largely unknown.…”

“…The therapeutic effects of i.c. ASCs transplantation were also evaluated in an APP/PS1 double Tg AD mouse model (21). The transplantation of ASCs reduced amyloid beta (Ab) deposition and restored the learning and memory function in APP/PS1 double Tg mice (21).…”

Stem Cell Transplantation for Traumatic Spinal Cord Injury: What Have We Learned from Previous Experience

“…MSCs, whether bone marrow derived or adipose derived have been shown to differentiate into neuron cells (8)(9)(10), Schwann Cells (11-13), neurotrophic factor secreting cells (14)(15), and glial cells (16). Researchers have been able to produce mature and functional dopaminergic neurons from induced pleuripotent stem cells (iPS) (17,18) and Wharton jelly derived MSCs (19).…”

Transdifferentiation potential of adipose-derived stem cells into neural lineage and their application

“…The same group demonstrated that ADSC are capable to alleviate symptoms of Alzheimer's disease and diminish cognitive decline through modulate microglial activation [32]. Chen et al, revealed that ADSCs transplantation in rat model of brain ischemia can promote neuronal regeneration by inhibiting the expression of Glial fibrillary acidic protein (GFAP) and increasing the expressions of Neuritin and NF-200 in the brain [33].…”