The Therapeutic Effects of Human Adipose-Derived Stem Cells in Alzheimer's Disease Mouse Models

2013 ◽  
Vol 13 (2-3) ◽  
pp. 99-102 ◽  
Author(s):  
Keun-A. Chang ◽  
Hee Jin Kim ◽  
Yuyoung Joo ◽  
Sungji Ha ◽  
Yoo-Hun Suh
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Mouse Models ◽  
Therapeutic Effects ◽  
Adipose Derived Stem Cells

scholarly journals The Preventive and Therapeutic Effects of Intravenous Human Adipose-Derived Stem Cells in Alzheimer’s Disease Mice

PLoS ONE ◽  
2012 ◽  
Vol 7 (9) ◽  
pp. e45757 ◽  
Author(s):  
Saeromi Kim ◽  
Keun-A Chang ◽  
Jeong a. Kim ◽  
Hyeong-Geun Park ◽  
Jeong Chan Ra ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Therapeutic Effects ◽  
Adipose Derived Stem Cells

scholarly journals Therapeutic Effects of Transplantation of As-MiR-937-Expressing Mesenchymal Stem Cells in Murine Model of Alzheimer's Disease

2015 ◽  
Vol 37 (1) ◽  
pp. 321-330 ◽  
Author(s):  
Zhen Liu ◽  
Cunfu Wang ◽  
Xiao Wang ◽  
Shunliang Xu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Murine Model ◽  
Social Recognition ◽  
Saline Control ◽  
Mouse Bone Marrow ◽  
Therapeutic Effects ◽  
Mrna Levels

Background/Aims: Alzheimer's disease (AD) is one of the most common dementias among aged people, and is clinically characterized by progressive memory loss, behavioral and learning dysfunction and cognitive deficits. So far, this is no cure for AD. A therapeutic effect of transplantation of mesenchymal stem cells (MSCs) into murine model of AD has been reported, but remains to be further improved. Brn-4 is a transcription factor that plays a critical role in neuronal development, whereas the effects of Brn-4 overexpression in transplanted MSCs on AD are unknown. Methods: MSCs were isolated from mouse bone marrow and induced to overexpress antisense of miRNA-937 (as-miR-937) through adeno-associated virus (AAV)-mediated transduction, and purified by flow cytometry based on expression of a GFP co-transgene in the cells. The Brn-4 levels in mouse MSCs were examined in miR-937-modified MSCs by RT-qPCR and by Western blot. These miR-937-modified MSCs were then transplanted into an APP/PS1 transgenic AD model in mice. The effects of saline control, MSCs and asmiR-937 MSCs on AD mice were examined by deposition of amyloid-beta peptide aggregates (Aβ), social recognition test (SR), Plus-Maze Discriminative Avoidance Task (PM-DAT) and the levels of Brain-derived neurotrophic factor (BDNF) in the mouse brain. Results: MSCs expressed high levels of Brn-4 transcripts but low levels of Brn-4 protein. Poor protein vs mRNA levels of Brn-4 in MSCs appeared to result from the presence of high levels of miR-937 in MSCs. miR-937 inhibited translation of Brn-4 mRNA through binding to the 3'-UTR of the Brn-4 mRNA in MSCs. Expression of as-miR-937 significantly increased Brn-4 protein levels in MSCs. Transplantation of as-miR-937-expressing MSCs significantly reduced the deposition of Aβ, increased the levels of BDNF, and significantly improved the appearance in SR and PM-DAT in AD mice. Conclusion: Overexpression of as-miR-937 in MSCs may substantially improve the therapeutic effects of MSCs on AD, possibly through augmenting Brn-4 levels in MSCs.

scholarly journals In vivoimaging of human adipose-derived stem cells in Alzheimer’s disease animal model

2013 ◽  
Vol 19 (5) ◽  
pp. 051206 ◽  
Author(s):  
Sungji Ha ◽  
Sangzin Ahn ◽  
Saeromi Kim ◽  
Yuyoung Joo ◽  
Young Hae Chong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Animal Model ◽  
Adipose Derived Stem Cells

scholarly journals The Therapeutic Effects of Adipose-Derived Stem Cells and Recombinant Peptide Pieces on Mouse Model of DSS Colitis

2018 ◽  
Vol 27 (9) ◽  
pp. 1390-1400 ◽  
Author(s):  
Reiko Iwazawa ◽  
Sayako Kozakai ◽  
Tsukasa Kitahashi ◽  
Kentaro Nakamura ◽  
Ken-ichiro Hata
Keyword(s):  
Stem Cells ◽  
Cell Therapy ◽  
Mouse Models ◽  
The Body ◽  
Toxicity Tests ◽  
Therapeutic Effects ◽  
Adipose Derived Stem Cells ◽  
Recombinant Peptide ◽  
General Toxicity

Cell therapies using adipose-derived stem cells (ADSCs) have been used to treat inflammatory bowel disease (IBD) in human and dog. We previously reported the CellSaic technique, which uses a recombinant scaffold to enhance the efficacy of cell therapy. To examine whether this technique can be applied to cell therapy for colitis, we evaluated the efficacy of CellSaic in colitis mouse models. Colitis mouse models were developed by administering dextran sulfate sodium (DSS) to C57BL/6 mice for 7 days. Then CellSaic comprising human/canine ADSCs (1.2 × 106 cells) or human/canine ADSCs only (1.2 × 106 cells) were administered to the mice. The body weights were measured, and the colon length measurements and histological evaluations were conducted at 7 days after administration. After in vitro culture of human ADSC (hADSC) CellSaic and hADSC spheroids in medium containing TNFα, the levels of the anti-inflammatory protein TSG-6 in each supernatant were measured. Furthermore, we conducted tumorigenicity and general toxicity tests of canine ADSC (cADSC) CellSaic in NOG mice for 8 weeks. In the colitis mouse models, the ADSC CellSaic group presented recovery of body weight and colon length compared with the ADSC-only group. Histological analysis showed that ADSC CellSaic decreased the number of inflammatory cells and repaired ulceration. In vitro, hADSC CellSaic secreted 3.1-fold more TSG-6 than the hADSCs. In addition, tumorigenicity and general toxicity of cADSC CellSaic were not observed. This study suggests that human and canine ADSC CellSaic has a therapeutic effect of colitis in human and dogs.

scholarly journals Efficacy of Adipose-Derived Stem Cells as a Potential Cellular Therapy of Alzheimer’s Disease: A Comprehensive Systematic Review

2021 ◽  
Vol 7 (4) ◽  
Author(s):  
Grady Krisandi ◽  
Rejoel Mangasa Siagian ◽  
Karina Karina ◽  
Imam Rosadi
Keyword(s):  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Neurodegenerative Diseases ◽  
Cellular Therapy ◽  
Phase 1 ◽  
Risk Of Bias ◽  
Cochrane Library ◽  
Adipose Derived Stem Cells

Context: Elderlies are more prone to neurodegenerative diseases. One of the most common neurodegenerative diseases with limited effective treatments available is Alzheimer’s disease (AD). Adipose-derived stem cells (ADSCs) with neuroregenerative and neuroprotective capabilities have shown great potential to serve as a potential cellular therapy for AD. Adipose-derived stem cells’ efficacy in the treatment of AD is evaluated in this systematic review. Data Sources: Literature search was performed via PubMed, Cochrane Library, ScienceDirect, Wiley Online Library, and EBSCOhost databases, selecting studies which evaluated the effect of ADSCs on AD from inception to 6 August 2020. The SYRCLE Risk of Bias tool was used to assess pre-clinical studies in animal models, and MINORS Risk of Bias tool was used to assess non-randomized phase 1 clinical trials. Conclusions: Overall, seven studies, including two in-vitro studies, four in-vivo mice model studies, and one non-randomized phase 1 clinical trial, were included in this systematic review. Adipose-derived stem cells showed significant potential, proven by their neuroregenerative (i.e., increased neurogenesis, synaptogenesis, synaptic and dendritic stability, and cognitive and spatial skills) and neuroprotective capabilities (i..e., decreased Aβ concentration, APP-CT concentration, P-tau concentration, number of amyloid plaques, oxidative stress, and neuron apoptosis when exposed to Aβ). Adipose-derived stem cells demonstrated promising efficacy in treating AD patients.

scholarly journals Exposure of Mesenchymal Stem Cells to an Alzheimer’s Disease Environment Enhances Therapeutic Effects

2020 ◽  
Author(s):  
Sang eon Park ◽  
Hyeong Seop Kim ◽  
Soo Jin Kwon ◽  
Min-Jeong Kim ◽  
Suk-joo Choi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Cell Death ◽  
Mesenchymal Stem Cells ◽  
Amyloid Beta ◽  
Therapeutic Effects ◽  
Human Mscs ◽  
Sequencing Data ◽  
Ubiquitin Conjugate

Abstract BackgroundMesenchymal stem cells (MSCs) have emerged as a promising tool for the treatment of Alzheimer’s disease (AD). Previous studies suggested that the co-culture of human MSCs with AD in an in vitro model reduced the expression of amyloid-beta 42 (Aβ42) in the medium as well as the overexpression of amyloid-beta (Aβ )-degrading enzymes such as neprilysin (NEP).MethodsIn this study, we focused on the role of primed MSCs (human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) exposed to an AD cell line via a co-culture system) in reducing the levels of Aβ and inhibiting cell death. ResultsWe demonstrated that mouse groups treated with naïve MSCs and primed MSCs showed significant reductions in cell death, ubiquitin conjugate levels, and Aβ levels, but the effects were greater in primed MSCs. Also, mRNA sequencing data analysis indicated that high levels of TGF-β induced primed-MSCs. Furthermore, treatment with TGF-β reduced Aβ expression in an AD transgenic mouse model. ConclusionAD environmental preconditioning is a promising strategy to reduce cell death and ubiquitin conjugate levels and maintain the stemness of MSCs. Further, these data suggest that human WJ-MSCs exposed to an AD environment may represent a promising and novel therapy for AD.

scholarly journals Exposure of Mesenchymal Stem Cells to an Alzheimer’s Disease Environment Enhances Therapeutic Effects

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Sang Eon Park ◽  
Hyeong Seop Kim ◽  
Soo Jin Kwon ◽  
Min-Jeong Kim ◽  
Suk-joo Choi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Cell Death ◽  
Mesenchymal Stem Cells ◽  
Amyloid Beta ◽  
Therapeutic Effects ◽  
Human Mscs ◽  
Sequencing Data ◽  
Ubiquitin Conjugate

Mesenchymal stem cells (MSCs) have emerged as a promising tool for the treatment of Alzheimer’s disease (AD). Previous studies suggested that the coculture of human MSCs with AD in an in vitro model reduced the expression of amyloid-beta 42 (Aβ42) in the medium as well as the overexpression of amyloid-beta- (Aβ-) degrading enzymes such as neprilysin (NEP). We focused on the role of primed MSCs (human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) exposed to an AD cell line via a coculture system) in reducing the levels of Aβ and inhibiting cell death. We demonstrated that mouse groups treated with naïve MSCs and primed MSCs showed significant reductions in cell death, ubiquitin conjugate levels, and Aβ levels, but the effects were greater in primed MSCs. Also, mRNA sequencing data analysis indicated that high levels of TGF-β induced primed-MSCs. Furthermore, treatment with TGF-β reduced Aβ expression in an AD transgenic mouse model. These results highlighted AD environmental preconditioning is a promising strategy to reduce cell death and ubiquitin conjugate levels and maintain the stemness of MSCs. Further, these data suggest that human WJ-MSCs exposed to an AD environment may represent a promising and novel therapy for AD.

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