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Nascent osteoblast matrix inhibits osteogenesis of human mesenchymal stem cells in vitro

Kolf, CM and Song, L and Helm, J and Tuan, RS (2015) Nascent osteoblast matrix inhibits osteogenesis of human mesenchymal stem cells in vitro. Stem Cell Research and Therapy, 6 (1).

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Introduction: Adult mesenchymal stem cells (MSCs) are considered promising candidates for cell-based therapies. Their potential utility derives primarily from their immunomodulatory activity, multi-lineage differentiation potential, and likely progenitor cell function in wound healing and repair of connective tissues. However, in vitro, MSCs often senesce and spontaneously differentiate into osteoblasts after prolonged expansion, likely because of lack of regulatory microenvironmental signals. In vivo, osteoblasts that line the endosteal bone marrow surface are in close proximity to MSCs in the marrow stroma and thus may help to regulate MSC fate. Methods: We examined here how osteogenic differentiation of MSCs in vitro is affected by exposure to osteoblastic cells (OBCs). Human bone marrow MSCs were exposed to OBCs, derived by induced osteogenic differentiation of MSCs, either directly in contact co-cultures, or indirectly to OBC-conditioned medium or decellularized OBC extracellular matrix (ECM). Results: Our results showed that OBCs can act as negative regulators of MSC osteogenesis. mRNA expression profiling revealed that OBCs did not affect MSC osteogenesis in direct contact cultures or via secreted factors. However, seeding MSCs on decellularized OBC ECM significantly decreased expression of several osteogenic genes and maintained their fibroblastic morphologies. Proteomic analysis identified some of the candidate protein regulators of MSC osteogenesis. Conclusions: These findings provide the basis for future studies to elucidate the signaling mechanisms responsible for osteoblast matrix-mediated regulation of MSC osteogenesis and to better manipulate MSC fate in vitro to minimize their spontaneous differentiation.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Kolf, CM
Song, L
Helm, J
Tuan, RSrst13@pitt.eduRST13
Date: 22 December 2015
Date Type: Publication
Journal or Publication Title: Stem Cell Research and Therapy
Volume: 6
Number: 1
DOI or Unique Handle: 10.1186/s13287-015-0223-x
Schools and Programs: School of Medicine > Orthopaedic Surgery
Refereed: Yes
Date Deposited: 22 Aug 2016 14:56
Last Modified: 30 Mar 2021 15:55


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