Home » Key Stem Cells Research Articles » 3D microenvironment of collagen hydrogel enhances the release of neurotrophic factors from human umbilical cord blood cells and stimulates the neurite outgrowth of human neural precursor cells

3D microenvironment of collagen hydrogel enhances the release of neurotrophic factors from human umbilical cord blood cells and stimulates the neurite outgrowth of human neural precursor cells

Significance statement

 

Stem cells play key roles in the regenerative process of damaged and diseased tissues through a controlled stem cell trans-differentiation into a cell type of interest. However, recently, a modulatory role of stem cells i.e., immune-modulation of anti-scar formation and nerve protection by their secreted cytokines and neurotrophic factors, has been highlighted. UCB cells have also shown to produce several neurotrophic factors, including nerve growth factors (NGFs), brain-derived neurotrophic factors (BDNFs), ciliary neurotrophic factors (CNTFs), neurotrophin-3 (NT3), and -4 (NT4) [15]. Therefore, UCB cells are considered as a possible therapeutic cell source for the treatment of neurotrauma and neurodegenerative diseases.

Here we thus hope to make full use of the UCB cells for this neural repair and regenerative purposes. In particular, we consider the culture microenvironments of UCB cells would significantly affect their biological functions, particularly their releasing behaviors of neurotrophic factors. We introduce 3-dimensional (3D) hydrogel made of collagen to culture UCB cells. 3D hydrogel environment is considered to mimic the native soft tissue structure, providing stem cells appropriate physical and chemical cues for adherence, spreading, growth and even switch to a lineage differentiation. When compared to 2D culture, the 3D hydrogel culture significantly enhanced the expression of a series of neutrophic factors, including neurotrophin-4, nerve growth factor, brain-derived neurotrophic factor, and ciliary neurotrophic factor as verified by the gene and protein analysis. To verify the effects of neurotrophic factors secretion, we allowed an indirect interaction of the UCB-environment with human neuronal precursor cells (hNPCs). Results showed significantly enhanced directional neurite outgrowth and neuronal differentiation of hNPCs.

In conclusion, the main benefit of using the 3D collagen hydrogel is to stimulate the secretion of neutropic factors from stem cells and slowly provide them along with uncharacterized physical or chemical cues to nearby neural cells, which collectively would help to regenerate the damaged neural tissues. The present 3-D culture of UBC-MSCs in a collagen hydrogel therefore could provide a novel framework for the stem cell-based therapy. Collectively, our findings demonstrate that the collagen-based 3D hydrogel provides excellent microenvironment for UBC cells to release neurotrophic factors that will be ultimately useful for the neural repair and regeneration purposes.

3D microenvironment of collagen hydrogel enhances the release of neurotrophic factors from human umbilical cord blood cells

 

Journal Reference

Park JW1, Kang YD1, Kim JS1, Lee JH2, Kim HW3.

Biochem Biophys Res Commun. 2014 May 9;447(3):400-6.

1Department of Obstetrics and Gynecology, College of Medicine, College of Dentistry, Dankook University, Cheonan 330-714, South Korea and

2Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714, South Korea; Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, South Korea. Electronic address: [email protected] and

3Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714, South Korea; Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, South Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan 330-714, South Korea. Electronic address: [email protected]

 

Abstract

The umbilical cord blood (UCB) cells have been reported to secrete therapeutic signals, including a series of neurotrophic factors. This suggests the cell source provides suitable therapeutic environments for nerve regeneration that ultimately finds a possible cell therapy for nerve tissue. In this study, we observe a collagen hydrogel provides human UCB cells a proper 3D environment that stimulates the release of various neurotrophic factors. When compared to 2D culture, the 3D hydrogel culture significantly enhanced the expression of a series of neurotrophic factors, including neurotrophins, nerve growth factor, brain-derived neurotrophic factor, and ciliary neurotrophic factor as verified by the gene and protein analysis. To confirm the effects of neurotrophic factors secretion, we allowed an indirect interaction of the UCB-environment with human neural precursor cells (hNPCs). Results showed significantly enhanced neurite outgrowth of hNPCs. Collectively, our findings demonstrate that the collagen-based 3D hydrogel provides excellent environment for UCB-derived cells to release neurotrophic factors that will be ultimately useful for the neural repair and regeneration purposes.

Copyright © 2014 Elsevier Inc. All rights reserved.

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