Abstract

Skin is the largest organ of the human body and a possible source of stem cells for research and cell-based therapy. We have isolated a population of mesenchymal stem cell-like pluripotent cells from human epidermis, termed human (h) EMSCPCs. This preliminary study tested if these hEMSCPCs can be induced to differentiate into neural-like cells. Human EMSCPCs were first cultured for four to seven days in a serum-free neural stem cell (NSC) medium for pre-induction. During pre-induction, hEMSCPCs coalesced into dense spheres that resembled neural rosettes. In the presence of a conditioned differentiation medium, pre-induced cells took on the morphological characteristics of neural cells, including slender projections with inflated or claw-like ends that contacted the soma or projections of other cells as revealed by confocal microscopy. Moreover, these differentiating cells expressed the neural-specific markers β-III tubulin, MAP2, GFAP, and synapsin I as evidenced by immunocytochemistry. Both pre-induced hEMSCPCs and uninduced hEMSCPCs were labeled with CM-DiI and transplanted into the vitreous cavities of nude mice. Transplanted cells were examined four weeks later in frozen eyeball sections by immunofluorescence staining, which demonstrated superior retinal migration and neural differentiation of pre-induced cells. Our study is the first to demonstrate that hEMSCPCs possess the capacity to differentiate into neural-like cells, suggesting potential uses for the treatment of retinal diseases such as age-related macular degeneration.

Highlights

  • Neurological degenerative diseases like Alzheimer’s disease, Parkinson’s disease, and age-related macular degeneration are a group of chronic, diverse and progressive disorders

  • Cell precipitation was suspended in growth medium consisting of 80% DMEM (GIBCO, USA), 18% fetal bovine serum (FBS) (Si Jiqing Ltd., China), 10 ng/ml basic fibroblast growth factor (PERPO-TECH, USA), 2 ng/ml stem cell factor (SCF) (PERPO-TECH, USA), and 1% MEM nonessential amino acids (NEAA) (100 × solution, GIBCO, USA), and plated in T-25 cell culture flask, incubated at 37 ̊C in a 5% CO2 atmosphere

  • When cultured in growth medium, hEMSCPCs appeared as small spindle-shaped cells that adhered to the bottoms of culture flasks in a monolayer arranged in a vortex pattern (Figures 1(A) and (B))

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Summary

Introduction

Neurological degenerative diseases like Alzheimer’s disease, Parkinson’s disease, and age-related macular degeneration are a group of chronic, diverse and progressive disorders. Oxidative stress, neurotrophic factor deficiency, dysbolism and other unknown factors could cause a main pathological change of special neurons degeneration and loss, followed by demyelination of nerve fibers [1]. These pathophysiology leads to a decreased activity in the pathway of neural conduction, and results in disturbance of memory, learning, moving and other activities, which causes severe public health burden, in an aging population. The results of clinical trials testing single gene therapies for Parkinson’s disease were less than ideal [8,9]

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