Conditioned medium from amniotic cells protects striatal degeneration and ameliorates motor deficits in the R6/2 mouse model of Huntington's disease

Abstract

Inflammation significantly impacts the progression of Huntington's disease (HD) and the mutant HTT protein determines a pro‐inflammatory activation of microglia. Mesenchymal stem/stromal cells (MSC) from the amniotic membrane (hAMSC), and their conditioned medium (CM‐hAMSC), have been shown to possess protective effects in vitro and in vivo in animal models of immune‐based disorders and of traumatic brain injury, which have been shown to be mediated by their immunomodulatory properties.In this study, in the R6/2 mouse model for HD we demonstrate that mice treated with CM‐hAMSC display less severe signs of neurological dysfunction than saline‐treated ones. CM‐hAMSC treatment significantly delayed the development of the hind paw clasping response during tail suspension, reduced deficits in rotarod performance, and decreased locomotor activity in an open field test. The effects of CM‐hAMSC on neurological function were reflected in a significant amelioration in brain pathology, including reduction in striatal atrophy and the formation of striatal neuronal intranuclear inclusions. In addition, while no significant increase was found in the expression of BDNF levels after CM‐hAMSC treatment, a significant decrease of microglia activation and inducible nitric oxide synthase levels were observed. These results support the concept that CM‐hAMSC could act by modulating inflammatory cells, and more specifically microglia.

miRNA Reference Genes in Extracellular Vesicles Released from Amniotic Membrane-Derived Mesenchymal Stromal Cells

“…Moreover, and most importantly, it is rich in stromal cells (hAMSCs) with immunomodulatory and regenerative properties [10]. Due to these features, in different preclinical inflammatory disease models, hAMSCs and their conditioned medium (CM-hAMSC) have been successfully exploited, including for lung [11][12][13][14] and liver fibrosis [15], wound healing [16][17][18], collagen-induced arthritis [19,20], multiple sclerosis [19], inflammatory bowel disease, colitis [21], sepsis [19], traumatic brain injury [22], and Huntington's disease [23]. Accordingly, in vitro, we and others have demonstrated that hAMSCs and CM-hAMSC suppress the proliferation, inflammatory cytokine production, and functions of T lymphocytes [24,25], monocytes [18], dendritic cells [26], macrophages [18], and natural killer cells [27], while inducing a phenotype and functional switch of monocytes toward macrophages with anti-inflammatory pro-regenerative M2-like features [18,25], supporting the expansions of regulatory T cells [24,25].…”

Mesenchymal Stromal Cells’ Therapy for Polyglutamine Disorders: Where Do We Stand and Where Should We Go?

“…These capacities have been linked to the release of molecules like indoleamine 2,3-dioxygenase (IDO), prostaglandin E2, interleukin-10 (IL-10), human leukocyte antigen-G, TGF-β, and HGF (Dorronsoro et al, 2013 ). It has been demonstrated that the systemic administration of CM derived from amniotic membrane MSC ameliorates motor dysfunctions, brain pathology, and decreased microglial activation in HD animal model (Giampà et al, 2019 ).…”

Neuro-regenerative imidazole-functionalized GelMA hydrogel loaded with hAMSC and SDF-1α promote stem cell differentiation and repair focal brain injury

“…Tremendous treatment options have been attempted to treat TBI, among which stem cell replacement therapy is considered as a promising way to regenerate brain tissue [ 5 ]. Human amniotic mesenchymal stromal cells (hAMSCs) have attracted much attention since they are easily obtained without minimal ethical controversy [ 6 , 7 ]. Francesca et al have found that hAMSCs showed neuronal rescue and introduction of trophic factors in TBI, which are favorable to protect brain [ 8 ].…”

“…Francesca et al have found that hAMSCs showed neuronal rescue and introduction of trophic factors in TBI, which are favorable to protect brain [ 8 ]. Other researchers have found that hAMSCs treated-TBI present a significant decrease of microglia activation [ 6 ], as well as upregulation of vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) [ 9 ]. These results indicate that hAMSCs have great potential to protect the injured brain, reduce the loss of neurons, increase the expression of nutritional factors, and partially restore brain function.…”