Three‐dimensional collagenous niche and azacytidine selectively promote time‐dependent cardiomyogenesis from human bone marrow‐derived MSC spheroids

Endogenous adult cardiac regenerative machinery is not capable of replacing the lost cells following myocardial infarction, often leading to permanent alterations in structure‐function‐mechanical properties. Regenerative therapies based on delivering autologous stem cells within an appropriate 3D mi...

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Bibliographic Details
Published in:Biotechnology and bioengineering 2018-08, Vol.115 (8), p.2013-2026
Main Authors: Joshi, Jyotsna, Mahajan, Gautam, Kothapalli, Chandrasekhar R.
Format: Article
Language:English
Subjects:
5‐azacytidine
atomic force microscopy
Autografts
Azacytidine
Bone marrow
Cell culture
Cell interactions
Collagen
Collagen (type I)
collagen gels
Differentiation
Evolution
Gels
Genotypes
Homing
human bone marrow‐derived MSCs
Immunofluorescence
Matrix protein
Mechanical properties
Mesenchyme
Modulus of elasticity
Myocardial infarction
Phenotypes
Pore size
Porosity
Proteins
Signal transduction
Signaling
Spheroids
Stem cell transplantation
Stem cells
Stiffness
Structure-function relationships
Time dependence
Tissue engineering
Transplantation
Wnt protein
Wnt signaling
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Summary:Endogenous adult cardiac regenerative machinery is not capable of replacing the lost cells following myocardial infarction, often leading to permanent alterations in structure‐function‐mechanical properties. Regenerative therapies based on delivering autologous stem cells within an appropriate 3D milieu could meet such demand, by enabling homing and directed differentiation of the transplanted cells into lost specialized cell populations. Since type I collagen is the predominant cardiac tissue matrix protein, we here optimized the 3D niche which could promote time‐dependent evolution of cardiomyogenesis from human bone marrow‐derived mesenchymal stem cells (BM‐MSC). 3D collagen gel physical and mechanical characteristics were assessed using SEM and AFM, respectively, while the standalone and combined effects of collagen concentration, culture duration, and 5‐azacytidine (aza) dose on the phenotype and genotype of MSC spheroids were quantified using immunofluorescence labeling and RT‐PCR analysis. Increasing collagen concentration led to a significant increase in Young's modulus (p 
ISSN:0006-3592
1097-0290
DOI:10.1002/bit.26714