All Stem Cells Japan

Alzheimer’s disease (AD), the most common form of dementia in people over 65 years, is an irreversible progressive neurodegenerative disease, leading to severe incapacity and death. The hallmark neuropathological features of AD include extracellular as well as intracellular deposition of β- amyloid or Abeta (Aβ) protein, the formation of intracellular neurofibrillary tangles (NFT) and widespread neuronal loss, which cause characteristic neuronal deficits in the cerebral cortical and hippocampal areas associated with cognitive decline. According to the latest
estimation, it suggests that more than 35 million people worldwide suffer from AD today, with predictions that there could be more 125 million patients with AD by 2050. Unfortunately, the conventional therapeutic methods can only alleviate some clinical symptoms, and no cure or disease-modifying treatments against AD are currently available.
Recently, stem cells transplantation, including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and tissue-derived stem cells, such as bone marrow (BM)-and adipose-derived stem cells, has received considerable attention asa potential approach to various diseases, including AD. There is now considerable preclinical literature on the possible benefits of stem cells transplantation against AD.

Stem cells transplantation could lead to improve cognitive and memory performances and increased neuronal survival as a result of the decrease in β-amyloid plaques, neurofibrillary tangles, neurodegeneration, and microglia activation in animal models of AD. Moreover, neural stem cells could ameliorate complex behavioral deficits associated with widespread AD pathology via BDNF.[1] In vitro and in vivo, the transplantations of bone marrow-derived mesenchymal stem cells (BM-MSCs) were shown to ameliorate Aβ-induced neurotoxicity and cognitive decline by inhibiting apoptotic cell death and oxidative stress in the hippocampus. It has been also demonstrated that human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) transplantation could rescue the impaired memory function in AD mouse by reduction of apoptosis and modulation of oxidative stress.[2] Human amniotic epithelial cells (HAECs) transplantation could significantly ameliorate spatial memory deficits in transgenic mice, as well as increased acetylcholine levels and the number of hippocampal cholinergic neuritis.
Although stem cells show a strong candidate for treating AD in animal models, however, further studies are needed to determine the appropriate conditions to improve the therapeutic effects for AD, such as, which type of stem cells and from what source is best to implant, how many are needed, and where the implanted cells need to be transplanted into. Moreover, to inform decisions regarding the design and conduct of subsequent clinical trials, whether the magnitude of integrative and protective effects is large enough to be potentially clinically meaningful, and whether reports of efficacy in animal models are potentially biased in favor of positive results is also need to be investigated. Therefore, we report a systematic review and meta-analysis of data from controlled studies testing the efficacy of stem cells as a treatment in animal models of AD.

(1) to identify all animal experiments describing the efficacy of stem cells based therapies in models of AD,
(2) to systematically review the literature describing the effect of stem cells based therapies on cognitive impairment in animal models of AD,
(3) to perform a meta-analysis using the DerSimonian and Laird random effects model,
(4) to provide empirical evidence of biological factors associated with greater efficacy,
(5) and to provide an assessment for the presence and impact of possible publication bias .