Early immunomodulatory effects of implanted human perivascular stromal cells during bone formation

Carolyn A Meyers, Jiajia Xu, Lei Zhang, Greg Asatrian, Catherine Ding, Noah Yan, Kristen Broderick, Justin Sacks, Raghav Goyal, Xinli Zhang, Kang Ting, Bruno Péault, Chia Soo, Aaron W James

Research output: Contribution to journalArticlepeer-review

Abstract

Human perivascular stem/stromal cells (PSC) are a multipotent mesodermal progenitor cell population defined by their perivascular residence. PSC are most commonly derived from subcutaneous adipose tissue, and recent studies have demonstrated the high potential for clinical translation of this fluorescence activated cell sorting (FACS) derived cell population for bone tissue engineering. Specifically, purified PSC induce greater bone formation than unpurified stroma taken from the same patient sample. Here, we examined the differences in early innate immune response to human PSC or unpurified stroma (stromal vascular fraction, SVF) during the in vivo process of bone formation. Briefly, SVF or PSC from the same patient sample were implanted intramuscularly in the hindlimb of SCID mice using an osteoinductive demineralized bone matrix carrier. Histologic examination of early inflammatory infiltrates was examined by H&E and immunohistochemical staining (Ly-6G, F4/80). Results showed significantly greater neutrophilic and macrophage infiltrates within and around SVF in comparison to PSC laden implants. Differences in early postoperative inflammation among SVF laden implants was associated with reduced osteogenic differentiation and bone formation. Similar findings were recapitulated with PSC implantation in immune-competent mice. Exaggerated postoperative inflammation was associated with increased IL-1α, IL-1β, IFN-γ and TNF-α gene expression among SVF samples, and conversely increased IL-6 and IL-10 expression among PSC samples. These data document a robust immunomodulatory effect of implanted PSC, and an inverse correlation between host inflammatory cell infiltration and stromal progenitor cell mediated ossification.

Original languageEnglish
JournalTissue Engineering, Part A
Early online date6 Jul 2017
DOIs
Publication statusE-pub ahead of print - 6 Jul 2017

Keywords

  • Journal Article

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