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Author Notes:

Johnna S. Temenoff, W.H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, US; johnna.temenoff@bme.

Subjects:

Research Funding:

The authors wish to acknowledge funding from NIH R21 EB009153 as well as the NSF Stem Cell Biomanufacturing IGERT (DGE 0965945) to TER.

Primary human MSCs were provided by the Texas A&M Health Science Center College of Medicine, Institute for Regenerative Medicine at Scott and White Healthcare through a grant from NCRR of the NIH (P40RR017447).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell Biology
  • GLUCOSE-CONCENTRATIONS ALTER
  • HYDROGELS
  • DIFFERENTIATION
  • MECHANISMS
  • FAT
  • PATHOGENESIS
  • MODULATION
  • INSULIN
  • DISEASE
  • SYSTEMS

Interactions between mesenchymal stem cells, adipocytes, and osteoblasts in a 3D tri-culture model of hyperglycemic conditions in the bone marrow microenvironment

Journal Title:

Integrative Biology

Volume:

Volume 6, Number 3

Publisher:

, Pages 324-337

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Recent studies have found that uncontrolled diabetes and consequential hyperglycemic conditions can lead to an increased incidence of osteoporosis. Osteoblasts, adipocytes, and mesenchymal stem cells (MSCs) are all components of the bone marrow microenvironment and thus may have an effect on diabetes-related osteoporosis. However, few studies have investigated the influence of these three cell types on each other, especially in the context of hyperglycemia. Thus, we developed a hydrogel-based 3D culture platform engineered to allow live-cell retrieval in order to investigate the interactions between MSCs, osteoblasts, and adipocytes in mono-, co-, and tri-culture configurations under hyperglycemic conditions for 7 days of culture. Gene expression, histochemical analysis of differentiation markers, and cell viability were measured for all cell types, and MSC-laden hydrogels were degraded to retrieve cells to assess their colony-forming capacity. Multivariate models of gene expression data indicated that primary discrimination was dependent on the neighboring cell type, validating the need for co-culture configurations to study conditions modeling this disease state. MSC viability and clonogenicity were reduced when mono- and co-cultured with osteoblasts at high glucose levels. In contrast, MSCs showed no reduction of viability or clonogenicity when cultured with adipocytes under high glucose conditions, and the adipogenic gene expression indicates that cross-talk between MSCs and adipocytes may occur. Thus, our unique culture platform combined with post-culture multivariate analysis provided a novel insight into cellular interactions within the MSC microenvironment and highlights the necessity of multi-cellular culture systems for further investigation of complex pathologies such as diabetes and osteoporosis.

Copyright information:

© The Royal Society of Chemistry 2014.

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