Three-dimensional Collagenous Niche and Azacytidine Selectively Promote Time-dependent Cardiomyogenesis from Human Bone Marrow-derived MSC Spheroids

ORCID ID

http://orcid.org/0000-0001-8450- 0640

Document Type

Article

Publication Date

8-2018

Publication Title

Biotechnology and Bioengineering

Abstract

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

Comments

NSF-CBET, Grant number: 1337859

Cellular and Molecular Medicine Specialization fellowship at CSU; NSF-DMR, Grant number: 1126126

Volume

115

Issue

8

DOI

10.1002/bit.26714

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