A microphysiological system for studying human bone biology under simultaneous control of oxygen tension and mechanical loading

Scheinpflug, Julia; Höfer, Chris Tina; Schmerbeck, Sarah S.; Steinfath, Matthias; Doka, Jennifer; Tesfahunegn, Yonatan Afework; Violet, Norman; Renko, Kostja; Gulich, Konrad; John, Thilo; Schneider, Marlon R.; Wistorf, Elisa; Schönfelder, Gilbert; Schulze, Frank

doi:10.1039/d3lc00154g

Cited by 2 publications

(1 citation statement)

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“…Overall, the increased secretion of TGF-β1, TIMP2, and VEGF in osteogenically differentiated BM-MSCs from PAO patients compared with those from THA patients may be beneficial for future therapies in the context of bone repair and endochondral ossification. The application of BM-MSCs from PAO samples in the context of cell therapies for bone healing or to stimulate bone formation of impaired periprosthetic bone requires preclinical testing in advanced and multicellular human in vitro models [ 57 – 59 ] and in vivo testing [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

Bone marrow from periacetabular osteotomies as a novel source for human mesenchymal stromal cells

Handke,

Rakow,

Singer

et al. 2023

Stem Cell Res Ther

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Background Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are used in regenerative medicine and related research involving immunomodulatory, anti-inflammatory, anti-fibrotic and regenerative functions. Isolation of BM-MSCs from samples obtained during total hip arthroplasty (THA) is routinely possible. Advanced age and comorbidities of the majority of patients undergoing THA limit their applicability. Our study aimed to evaluate the potential of bone marrow obtained during periacetabular osteotomy (PAO) as a novel source of BM-MSCs from young donors by analyzing cell yield and cell characteristics. Methods Bone samples were obtained from the anterior Os ilium or superior Os pubis during PAO and from the femoral cavity during primary THA. Isolation of bone marrow-derived mononuclear cells (BM-MNCs) was performed by density gradient centrifugation. The samples from PAO and THA patients were compared in terms of BM-MSC yield, colony formation and the proportion of BM-MSCs within the BM-MNC population using flow cytometry analysis. The cells were characterized based on the expression of BM-MSC-specific surface markers. The functionality of the cells was compared by quantifying post-thaw viability, metabolic activity, proliferation capacity, senescence-associated beta galactosidase (SA-β-gal) expression, trilineage differentiation potential and major secretome proteins. Results Isolation of BM-MNCs was possible in a reliable and reproducible manner when using bone from PAO containing more than 0.24 g bone marrow. PAO patients were younger than patients of the THA group. Bone obtained during PAO contained less bone marrow and led to a lower BM-MSC number after the first cell culture passage compared to BM-MSCs obtained during THA. BM-MSCs from PAO samples are characterized by a higher proliferation capacity. This results in a higher yield in cell culture passage two, when normalized to the sample weight. BM-MSCs from PAO patients showed increased secretion of TGF-β1, TIMP2, and VEGF upon osteogenic differentiation. BM-MSCs from PAO and THA patients revealed similar results regarding the onset of SA-β-gal expression and trilineage differentiation capacity. Conclusions We suggest that bone obtained during PAO is a promising novel source for BM-MSCs from young donors. Limited absolute cell yield due to low sample weight must be considered in early cell culture passages and might be critical for the range of clinical applications possible for BM-MSCs from this source. The higher proliferation capacity and increased growth factor secretion of BM-MSCs from young donors may be beneficial for future regenerative cell therapies, in vitro models, and tissue engineering.

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Section: Discussionmentioning

confidence: 99%

Bone marrow from periacetabular osteotomies as a novel source for human mesenchymal stromal cells

Handke,

Rakow,

Singer

et al. 2023

Stem Cell Res Ther

Self Cite

View full text Add to dashboard Cite

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Estrogen and estrogen receptors mediate the mechanobiology of bone disease and repair

Shi,

Morgan

2024

Bone

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A microphysiological system for studying human bone biology under simultaneous control of oxygen tension and mechanical loading

Abstract: We present a microphysiological system with the unique ability to combine perfusion, regulation of oxygen tension, and mechanical loading to culture bone tissue constructs under physiological conditions.

Cited by 2 publications

References 64 publications

Bone marrow from periacetabular osteotomies as a novel source for human mesenchymal stromal cells

Bone marrow from periacetabular osteotomies as a novel source for human mesenchymal stromal cells

Estrogen and estrogen receptors mediate the mechanobiology of bone disease and repair

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