Soluble intracellular adhesion molecule-1 secreted by human umbilical cord blood-derived mesenchymal stem cell reduces amyloid-β plaques

Abstract

Presently, co-culture of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) with BV2 microglia under amyloid-β42 (Aβ42) exposure induced a reduction of Aβ42 in the medium as well as an overexpression of the Aβ-degrading enzyme neprilysin (NEP) in microglia. Cytokine array examinations of co-cultured media revealed elevated release of soluble intracellular adhesion molecule-1 (sICAM-1) from hUCB-MSCs. Administration of human recombinant ICAM-1 in BV2 cells and wild-type mice brains induced NEP expression in time- and dose-dependent manners. In co-culturing with BV2 cells under Aβ42 exposure, knockdown of ICAM-1 expression on hUCB-MSCs by small interfering RNA (siRNA) abolished the induction of NEP in BV2 cells as well as reduction of added Aβ42 in the co-cultured media. By contrast, siRNA-mediated inhibition of the sICAM-1 receptor, lymphocyte function-associated antigen-1 (LFA-1), on BV2 cells reduced NEP expression by ICAM-1 exposure. When hUCB-MSCs were transplanted into the hippocampus of a 10-month-old transgenic mouse model of Alzheimer's disease for 10, 20, or 40 days, NEP expression was increased in the mice brains. Moreover, Aβ42 plaques in the hippocampus and other regions were decreased by active migration of hUCB-MSCs toward Aβ deposits. These data suggest that hUCB-MSC-derived sICAM-1 decreases Aβ plaques by inducing NEP expression in microglia through the sICAM-1/LFA-1 signaling pathway.

Secretion of immunoregulatory cytokines by mesenchymal stem cells

“…Hypothetically, the lack of such a requirement for bone marrow-derived MSCs suggests acquisition of varying functions of MSCs according to the tissue localization. Furthermore, the importance of sICAM secreted from human umbilical cord-derived MSCs for microglia functioning and neuronal survival is depicted in a model of Alzheimer's disease [222] . Insufficiently explored, the paracrine function of sICAM seems to counteract the classical biological function of membrane ICAM by preventing leukocyte interactions.…”

“…Limited data demonstrate that some but not all MSCs are a source of sICAM. Profiles of cytokine arrays revealed high expression of sICAM from human MSCs derived from umbilical cord and deciduas [221,222] and null expression from bone marrow-derived MSCs [221] . The exact physiological role of sICAM in health and pathology is still not completely revealed but reports demonstrate its potential to stimulate endothelial cell differentiation in conditions with angiogenic growth in tumorigenesis [223] .…”

Anti-apoptotic Effects of Human Wharton's Jelly-derived Mesenchymal Stem Cells on Skeletal Muscle Cells Mediated via Secretion of XCL1

“…Further investigations on human MSC paracrine factors are required to gain complete understanding about the underlying therapeutic mechanisms of MSCs and develop novel treatment strategies employing recombinant proteins. [17][18][19] In this study, we investigated whether human Wharton's jellyderived MSCs (WJ-MSCs) could rescue both in vitro and in vivo models of skeletal muscle from cell death via paracrine activity. Furthermore, we identified chemokine (C motif) ligand (XCL1) as the key WJ-MSCs derived paracrine factor that mediates antiapoptotic effect.…”

“…For example, the paracrine action of human MSC has been demonstrated to prevent cell death and induce proliferation of endogenous progenitor cells. [17][18][19][20][21] Therefore, human MSCs have been described as injury drug store. 22,23 Lately, numerous paracrine factors have been identified through proteomic approaches.…”

Stem Cells for Neuro-regeneration: State of the Art

“…Delivery of neurotrophic factors using NSCs transplantation as neprilysin, plasmin, insulin degrading enzyme and cathepsin B, is shown to be a very effective strategy in approach to AD [76] as these factors helps to decrease amyloid-beta (Aβ) protein level in mice models [84. Using Adipose derived Stem cells (ADSCs) is promising source for neuroregeneration in AD model , Intracerebral administration of ADSCs showed increase in level of Aβ protein level thus leads to restore spatial cognitive abilities in APP/PS1 double transgenic mice [85], in another type of AD model, IV administration of ADSCs decrease dementia symptoms [86,87].…”