Stem Cell Institute Philippines

novel inductions for the future...

Stem Cell Treatment for Huntington's Disease is an Option at ASCI

Stem Cell Treatment for Huntington's Disease

 

 

 

 

 

 

 

 

 

 

Stem Cell Treatment for Huntington's Disease is an Option at ASCI

 

Related Articles Human-to-mouse prion-like propagation of mutant huntingtin protein. Acta Neuropathol. 2016 Oct;132(4):577-92 Authors: Jeon I, Cicchetti F, Cisbani G, Lee S, Li E, Bae J, Lee N, Li L, Im W, Kim M, Kim HS, Oh SH, Kim TA, Ko JJ, Aubé B, Oueslati A, Kim YJ, Song J Abstract Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder of the central nervous system (CNS) that is defined by a CAG expansion in exon 1 of the huntingtin gene leading to the production of mutant huntingtin (mHtt). To date, the disease pathophysiology has been thought to be primarily driven by cell-autonomous mechanisms, but, here, we demonstrate that fibroblasts derived from HD patients carrying either 72, 143 and 180 CAG repeats as well as induced pluripotent stem cells (iPSCs) also characterized by 143 CAG repeats can transmit protein aggregates to genetically unrelated and healthy host tissue following implantation into the cerebral ventricles of neonatal mice in a non-cell-autonomous fashion. Transmitted mHtt aggregates gave rise to both motor and cognitive impairments, loss of striatal medium spiny neurons, increased inflammation and gliosis in associated brain regions, thereby recapitulating the behavioural and pathological phenotypes which characterizes HD. In addition, both in vitro work using co-cultures of mouse neural stem cells with 143 CAG fibroblasts and the SH-SY5Y human neuroblastoma cell line as well as in vivo experiments conducted in newborn wild-type mice suggest that exosomes can cargo mHtt between cells triggering the manifestation of HD-related behaviour and pathology. This is the first evidence of human-to-mouse prion-like propagation of mHtt in the mammalian brain; a finding which will help unravel the molecular bases of HD pathology as well as to lead to the development of a whole new range of therapies for neurodegenerative diseases of the CNS. PMID: 27221146 [PubMed - indexed for MEDLINE]
Read more...
Characterization of subventricular zone-derived progenitor cells from mild and late symptomatic YAC128 mouse model of Huntington's disease. Biochim Biophys Acta. 2017 Sep 19;: Authors: Silva AC, Ferreira IL, Hayden MR, Ferreiro E, Cristina Rego A Abstract Huntington's disease (HD) is caused by an expansion of CAG repeats in the HTT gene, leading to expression of mutant huntingtin (mHTT) and selective striatal neuronal loss, frequently associated with mitochondrial dysfunction and decreased support of brain-derived neurotrophic factor (BDNF). New neurons derived from the subventricular zone (SVZ) are apparently not able to rescue HD pathological features. Thus, we analyzed proliferation, migration and differentiation of adult SVZ-derived neural stem/progenitor cells (NSPC) from mild (6month-old (mo)) and late (10mo) symptomatic HD YAC128 mice expressing full-length (FL)-mHTT versus age-matched wild-type (WT) mice. SVZ cells derived from 6mo YAC128 mice exhibited higher migratory capacity and a higher number of MAP2+ and synaptophysin+cells, compared to WT cells; MAP2 labeling was enhanced after exposure to BDNF. However, BDNF-evoked neuronal differentiation was not observed in 10mo YAC128 SVZ-derived cells. Interestingly, 6mo YAC128 SVZ-derived cells showed increased intracellular Ca(2+) levels in response to KCl, which was potentiated by BDNF, evidencing the presence of differentiated neurons. In contrast, KCl depolarization-induced intracellular Ca(2+) increase in 10mo YAC128 SVZ-derived cells was shown to be increased only in BDNF-treated YAC128 SVZ-derived cells, suggestive of decreased differentiation capacity. In addition, BDNF-untreated NSPC from 10mo YAC128 mice exhibited lower mitochondrial membrane potential and increased mitochondrial Ca(2+) accumulation, in relation with NSPC from 6mo YAC128 mice. Data evidence age-dependent reduced migration and decreased acquisition of a neuronal phenotype, accompanied by decreased mitochondrial membrane potential in SVZ-derived cells from YAC128 mice through HD symptomatic phases. PMID: 28939435 [PubMed - as supplied by publisher]
Read more...