Conditioning of myoblast secretome using mesenchymal stem/stromal cell spheroids improves bone repair

Augustine M. Saiz, Marissa A. Gionet-Gonzales, Mark A Lee, Jonathan K Leach

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Local muscle loss associated with open fractures remains an obstacle to functional recovery and bone healing. Muscle cells secrete bioactive myokines that elicit autocrine and paracrine effects and initiate signaling pathways for regenerating damaged muscle and bone. Mesenchymal stem/stromal cells (MSCs)are under investigation for the regeneration of both muscle and bone through their potent secretome. Compared to monodisperse cells, MSC spheroids exhibit a more complex secretome with heightened therapeutic potential. We hypothesized that the osteogenic potential of myokines would be enhanced when myoblasts were exposed to the MSC spheroid secretome. Conditioned media from MSC spheroids increased osteogenic response of MC3T3 pre-osteoblasts compared to myokines from L6 myoblasts alone. This effect was synergistically enhanced when conditioned media of MSC spheroids was serially delivered to myoblasts and then osteoprogenitor cells in vitro. We then delivered myoblast-stimulated conditioned media in the presence or absence of syngeneic rat bone marrow stromal cells (rBMSCs)from alginate hydrogels to a rat critical-sized segmental defect. We observed increased bone formation in defects treated with conditioned media compared to rBMSCs alone, while bone formation was greatest in defects treated with both conditioned media and rBMSCs over 12 weeks. This foundational study demonstrates a novel approach for capitalizing on the paracrine signaling of muscle cells to promote bone repair and provides additional evidence of the synergistic interaction between muscle and bone.

Original languageEnglish (US)
Pages (from-to)151-159
Number of pages9
JournalBone
Volume125
DOIs
StatePublished - Aug 1 2019

Fingerprint

Myoblasts
Mesenchymal Stromal Cells
Bone and Bones
Conditioned Culture Medium
Muscles
Osteogenesis
Muscle Cells
Paracrine Communication
Open Fractures
Hydrogels
Osteoblasts
Regeneration

Keywords

  • Bone
  • Mesenchymal stem/stromal cell
  • Muscle
  • Myokines
  • Secretome

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

Cite this

Conditioning of myoblast secretome using mesenchymal stem/stromal cell spheroids improves bone repair. / Saiz, Augustine M.; Gionet-Gonzales, Marissa A.; Lee, Mark A; Leach, Jonathan K.

In: Bone, Vol. 125, 01.08.2019, p. 151-159.

Research output: Contribution to journalArticle

Saiz, Augustine M. ; Gionet-Gonzales, Marissa A. ; Lee, Mark A ; Leach, Jonathan K. / Conditioning of myoblast secretome using mesenchymal stem/stromal cell spheroids improves bone repair. In: Bone. 2019 ; Vol. 125. pp. 151-159.
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