Biomineralized Matrices Dominate Soluble Cues to Direct Osteogenic Differentiation of Human Mesenchymal Stem Cells through Adenosine Signaling

Heemin Kang, Yu Ru V. Shih, Shyni Varghese

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Stem cell differentiation is determined by a repertoire of signals from its microenvironment, which includes the extracellular matrix (ECM) and soluble cues. The ability of mesenchymal stem cells (MSCs), a common precursor for the skeletal system, to differentiate into osteoblasts and adipocytes in response to their local cues plays an important role in skeletal tissue regeneration and homeostasis. In this study, we investigated whether a bone-specific calcium phosphate (CaP) mineral environment could induce osteogenic differentiation of human MSCs, while inhibiting their adipogenic differentiation, in the presence of adipogenic-inducing medium. We also examined the mechanism through which the mineralized matrix suppresses adipogenesis of hMSCs to promote their osteogenic differentiation. Our results show that hMSCs cultured on mineralized matrices underwent osteogenic differentiation despite being cultured in the presence of adipogenic medium, which indicates the dominance of matrix-based cues of the mineralized matrix in directing osteogenic commitment of stem cells. Furthermore, the mineralized matrix-driven attenuation of adipogenesis was reversed with the inhibition of A2b adenosine receptor (A2bR), implicating a role of adenosine signaling in mineralized environment-mediated inhibition of adipogenesis. Such synthetic matrices with an intrinsic ability to direct differentiation of multipotent adult stem cells toward a targeted phenotype while inhibiting their differentiation into other lineages not only will be a powerful tool in delineating the role of complex microenvironmental cues on stem cell commitment but also will contribute to functional tissue engineering and their translational applications. (Figure Presented).

Original languageEnglish
Pages (from-to)1050-1061
Number of pages12
JournalBiomacromolecules
Volume16
Issue number3
DOIs
Publication statusPublished - 2015 Mar 9
Externally publishedYes

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Stem cells
Adenosine
Tissue homeostasis
Phosphate minerals
Tissue regeneration
Purinergic P1 Receptors
Osteoblasts
Calcium phosphate
Tissue engineering
Minerals
Bone

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

Cite this

Biomineralized Matrices Dominate Soluble Cues to Direct Osteogenic Differentiation of Human Mesenchymal Stem Cells through Adenosine Signaling. / Kang, Heemin; Shih, Yu Ru V.; Varghese, Shyni.

In: Biomacromolecules, Vol. 16, No. 3, 09.03.2015, p. 1050-1061.

Research output: Contribution to journalArticle

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