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Stem Cell Res. 2017 Oct;24:55-60. doi: 10.1016/j.scr.2017.08.011. Epub 2017 Aug 17.

Mechanical induction of dentin-like differentiation by adult mouse bone marrow stromal cells using compressive scaffolds.

Author information

1
Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
2
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
3
Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA; Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA 02138, USA. Electronic address: don.ingber@wyss.harvard.edu.

Abstract

Tooth formation during embryogenesis is controlled through a complex interplay between mechanical and chemical cues. We have previously shown that physical cell compaction of dental mesenchyme cells during mesenchymal condensation is responsible for triggering odontogenic differentiation during embryogenesis, and that expression of Collagen VI stabilizes this induction. In addition, we have shown that synthetic polymer scaffolds that artificially induce cell compaction can induce embryonic mandible mesenchymal cells to initiate tooth differentiation both in vitro and in vivo. As embryonic cells would be difficult to use for regenerative medicine applications, here we explored whether compressive scaffolds coated with Collagen VI can be used to induce adult bone marrow stromal cells (BMSCs) to undergo an odontogenic lineage switch. These studies revealed that when mouse BMSCs are compressed using these scaffolds they increase expression of critical markers of tooth differentiation in vitro, including the key transcription factors Pax9 and Msx1. Implantation under the kidney capsule of contracting scaffolds bearing these cells in mice also resulted in local mineralization, calcification and production of dentin-like tissue. These findings show that these chemically-primed compressive scaffolds can be used to induce adult BMSCs to undergo a lineage switch and begin to form dentin-like tissue, thus raising the possibility of using adult BMSCs for future tooth regeneration applications.

KEYWORDS:

Bone marrow stromal cells; Collagen VI; Dentin; Odontogenesis; PNIPAAm; Tissue engineering

PMID:
28841424
PMCID:
PMC5796538
DOI:
10.1016/j.scr.2017.08.011
[Indexed for MEDLINE]
Free PMC Article

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