Cell-secreted extracellular matrix influences cellular composition sequestered from unprocessed bone marrow aspirate for osteogenic grafts

Jenna N. Harvestine, Augustine M. Saiz, Jonathan K Leach

Research output: Contribution to journalArticle

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Abstract

Bone marrow aspirates provide a rich source of cells for use in tissue engineering of bone and other clinical indications. However, progenitor cells such as mesenchymal stem cells (MSCs) account for a small fraction of nucleated cells in bone marrow aspirate (BMA), requiring extensive culture expansion. Accessory cell populations such as endothelial or hematopoietic cells can potentiate the bone-forming potential of MSCs, and cell-secreted extracellular matrix (ECM) can increase cell seeding efficiency and osteogenic differentiation of heterogeneous cell populations. In this study, we hypothesized that cell-secreted ECM could be used to sequester MSCs and accessory cells from BMA for bone regeneration. To generate 3D implantable constructs, BMA was resuspended in media with or without type I collagen or ECM and injected into a perfusion bioreactor system. The addition of protein coatings increased cell seeding efficiency compared to uncoated scaffolds. Compared to fresh BMA, the culture of BMA on all scaffolds reduced the proportion of CD45+ myeloid cells and increased CD31+CD45- endothelial cells. Compared to uncoated scaffolds, we observed a 143- and 30-fold increase in MSCs when fresh BMA was cultured on ECM- or collagen-coated scaffolds, respectively. Upon subcutaneous implantation, ECM-coated scaffolds promoted cell survival and early vascularization. However, bone formation was comparable across all implant groups, suggesting additional osteogenic cues are necessary to increase the bone forming potential of fresh BMA. These results motivate further investigation into strategies which elicit more robust bone regeneration by tissue aspirates.

Original languageEnglish (US)
Pages (from-to)2091-2101
Number of pages11
JournalBiomaterials Science
Volume7
Issue number5
DOIs
StatePublished - May 1 2019

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Grafts
Bone
Chemical analysis
Scaffolds
Stem cells
Cells
Accessories
Collagen
Endothelial cells
Scaffolds (biology)
Collagen Type I
Bioreactors
Tissue engineering
Cell culture
Tissue

ASJC Scopus subject areas

  • Biomedical Engineering
  • Materials Science(all)

Cite this

Cell-secreted extracellular matrix influences cellular composition sequestered from unprocessed bone marrow aspirate for osteogenic grafts. / Harvestine, Jenna N.; Saiz, Augustine M.; Leach, Jonathan K.

In: Biomaterials Science, Vol. 7, No. 5, 01.05.2019, p. 2091-2101.

Research output: Contribution to journalArticle

Harvestine, Jenna N. ; Saiz, Augustine M. ; Leach, Jonathan K. / Cell-secreted extracellular matrix influences cellular composition sequestered from unprocessed bone marrow aspirate for osteogenic grafts. In: Biomaterials Science. 2019 ; Vol. 7, No. 5. pp. 2091-2101.
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