Stem‐Cell Challenges in the Treatment of Alzheimer's Disease: A Long Way from Bench to Bedside

Abstract

Alzheimer's disease (AD) is the most prevalent type of dementia, and its neuropathology is characterized by deposition of insoluble β-amyloid peptides, intracellular neurofibrillary tangles, and the loss of diverse neurons. Current pharmacological treatments for AD relieve symptoms without affecting the major pathological characteristics of the disease. Therefore, it is essential to develop new and effective therapies. Stem-cell types include tissue-specific stem cells, such as neural stem cells and mesenchymal stem cells, embryonic stem cells derived from blastocysts, and induced pluripotent stem cells (iPSCs) reprogrammed from somatic cells. Recent preclinical evidence suggests that stem cells can be used to treat or model AD. The mechanisms of stem cell based therapies for AD include stem cell mediated neuroprotection and trophic actions, antiamyloidogenesis, beneficial immune modulation, and the replacement of the lost neurons. iPSCs have been recently used to model AD, investigate sporadic and familial AD pathogenesis, and screen for anti-AD drugs. Although considerable progress has been achieved, a series of challenges must be overcome before stem cell based cell therapies are used clinically for AD patients. This review highlights the recent experimental and preclinical progress of stem-cell therapies for AD, and discusses the translational challenges of their clinical application.

Design Advances in Particulate Systems for Biomedical Applications

“…Adequate cell types should be selected and integrated in the particulate systems according to the needs of the patients. The use of primary cells, [ 33 ] stem cells [34][35][36] and bioengineered cells [ 37,38 ] are considered a valuable strategy for treatment of several diseases or even for stimulating the regeneration of Figure 1. The chemistry at surface and bulk levels as well as the physical features such as mechanical properties, size, porosity, surface topography/texture, shape and compartmentalization should be carefully considered during the design/engineering of particulate systems for biomedical applications.…”

Wharton’s Jelly-derived mesenchymal stem cells alleviate memory deficits and reduce amyloid-β deposition in an APP/PS1 transgenic mouse model

“…However, harvesting BM-MSCs is an invasive procedure, and the yield of viable stem cells is low. These shortcomings limit their usage in clinic [3]. Wharton's Jelly-derived mesenchymal stem cells (WJ-MSCs) have gained much attention since they have a sufficiently high cell yield, without an invasive harvesting procedure and any ethical concern.…”

Transplantation of human umbilical cord blood-derived mononuclear cells induces recovery of motor dysfunction in a rat model of Parkinson's disease

“…Nevertheless, some studies reported that the transplanted NSCs overexpressing GDNF or BDNF or NGF improved the locomotive or memory deficits of the animal models with PD, amyotrophic lateral sclerosis, and Alzheimer's disease, probably because of secreted growth factors playing major neurorestorative effects in these studies. 29,[34][35][36] The compositions of the hUCB-MNCs are still not uniform. One study showed that the hUCB-MNCs contain different stem cells and CD34/CD45 is about 60%.…”