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Nanoparticle technology and stem cell therapy team up against neurodegenerative disorders.

ABSTRACT: The convergence of nanoparticles and stem cell therapy holds great promise for the study, diagnosis, and treatment of neurodegenerative disorders. Researchers aim to harness the power of nanoparticles to regulate cellular microenvironment, improve the efficiency of cell and drug delivery to the brain, and enhance the survival of stem cell transplants. Understanding the various properties of different nanoparticles is key to applying them to clinical therapies; the many distinct types of nanoparticles offer unique capacities for medical imaging, diagnosis, and treatment of neurodegeneration disorders. In this review we introduce the biology of Alzheimer's, Parkinson's Disease, and amyotrophic lateral sclerosis, and discuss the potentials and shortcomings of metal, silica, lipid-based, polymeric, and hydrogel nanoparticles for diagnosis and treatment of neurodegenerative disorders. We then provide an overview of current strategies in stem cell therapies and how they can be combined with nanotechnology to improve clinical outcomes.

SUBMITTER: Vissers C

PROVIDER: S-EPMC6703981 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Nanoparticle technology and stem cell therapy team up against neurodegenerative disorders.

Vissers Caroline C Ming Guo-Li GL Song Hongjun H

Advanced drug delivery reviews 20190221

The convergence of nanoparticles and stem cell therapy holds great promise for the study, diagnosis, and treatment of neurodegenerative disorders. Researchers aim to harness the power of nanoparticles to regulate cellular microenvironment, improve the efficiency of cell and drug delivery to the brain, and enhance the survival of stem cell transplants. Understanding the various properties of different nanoparticles is key to applying them to clinical therapies; the many distinct types of nanopart ...[more]

PMID: 30797953

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Project description:With the technology of reprogramming somatic cells by introducing defined transcription factors that enables the generation of "induced pluripotent stem cells (iPSCs)" with pluripotency comparable to that of embryonic stem cells (ESCs), it has become possible to use this technology to produce various cells and tissues that have been difficult to obtain from living bodies. This advancement is bringing forth rapid progress in iPSC-based disease modeling, drug screening, and regenerative medicine. More and more studies have demonstrated that phenotypes of adult-onset neurodegenerative disorders could be rather faithfully recapitulated in iPSC-derived neural cell cultures. Moreover, despite the adult-onset nature of the diseases, pathogenic phenotypes and cellular abnormalities often exist in early developmental stages, providing new "windows of opportunity" for understanding mechanisms underlying neurodegenerative disorders and for discovering new medicines. The cell reprogramming technology enables a reverse engineering approach for modeling the cellular degenerative phenotypes of a wide range of human disorders. An excellent example is the study of the human neurodegenerative disease amyotrophic lateral sclerosis (ALS) using iPSCs. ALS is a progressive neurodegenerative disease characterized by the loss of upper and lower motor neurons (MNs), culminating in muscle wasting and death from respiratory failure. The iPSC approach provides innovative cell culture platforms to serve as ALS patient-derived model systems. Researchers have converted iPSCs derived from ALS patients into MNs and various types of glial cells, all of which are involved in ALS, to study the disease. The iPSC technology could be used to determine the role of specific genetic factors to track down what's wrong in the neurodegenerative disease process in the "disease-in-a-dish" model. Meanwhile, parallel experiments of targeting the same specific genes in human ESCs could also be performed to control and to complement the iPSC-based approach for ALS disease modeling studies. Much knowledge has been generated from the study of both ALS iPSCs and ESCs. As these methods have advantages and disadvantages that should be balanced on experimental design in order for them to complement one another, combining the diverse methods would help build an expanded knowledge of ALS pathophysiology. The goals are to reverse engineer the human disease using ESCs and iPSCs, generate lineage reporter lines and in vitro disease models, target disease related genes, in order to better understand the molecular and cellular mechanisms of differentiation regulation along neural (neuronal versus glial) lineages, to unravel the pathogenesis of the neurodegenerative disease, and to provide appropriate cell sources for replacement therapy. This article is part of a Special Issue entitled SI: PSC and the brain.

Project description:BackgroundStem/progenitor cells (SPCs) demonstrate neuro-regenerative potential that is dependent upon their humoral activity by producing various trophic factors regulating cell migration, growth, and differentiation. Herein, we compared the expression of neurotrophins (NTs) and their receptors in specific umbilical cord blood (UCB) SPC populations, including lineage-negative, CD34(+), and CD133(+) cells, with that in unsorted, nucleated cells (NCs).Methods and resultsThe expression of NTs and their receptors was detected by QRT-PCR, western blotting, and immunofluorescent staining in UCB-derived SPC populations (i.e., NCs vs. lineage-negative, CD34(+), and CD133(+) cells). To better characterize, global gene expression profiles of SPCs were determined using genome-wide RNA microarray technology. Furthermore, the intracellular production of crucial neuro-regenerative NTs (i.e., BDNF and NT-3) was assessed in NCs and lineage-negative cells after incubation for 24, 48, and 72 h in both serum and serum-free conditions. We discovered significantly higher expression of NTs and NT receptors at both the mRNA and protein level in lineage-negative, CD34(+), and CD133(+) cells than in NCs. Global gene expression analysis revealed considerably higher expression of genes associated with the production and secretion of proteins, migration, proliferation, and differentiation in lineage-negative cells than in CD34(+) or CD133(+) cell populations. Notably, after short-term incubation under serum-free conditions, lineage-negative cells and NCs produced significantly higher amounts of BDNF and NT-3 than under steady-state conditions. Finally, conditioned medium (CM) from lineage-negative SPCs exerted a beneficial impact on neural cell survival and proliferation.ConclusionsCollectively, our findings demonstrate that UCB-derived SPCs highly express NTs and their relevant receptors under steady-state conditions, NT expression is greater under stress-related conditions and that CM from SPCs favorable influence neural cell proliferation and survival. Understanding the mechanisms governing the characterization and humoral activity of subsets of SPCs may yield new therapeutic strategies that might be more effective in treating neurodegenerative disorders.

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Nanoparticle technology and stem cell therapy team up against neurodegenerative disorders.

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Nanoparticle technology and stem cell therapy team up against neurodegenerative disorders.

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