Identification of Bone Marrow-Derived Soluble Factors Regulating Human Mesenchymal Stem Cells for Bone Regeneration.
Maintaining properties of human bone marrow-derived mesenchymal stem cells (BMSCs) in culture for regenerative applications remains a great challenge. An emerging approach of constructing a culture environment mimicking the bone marrow niche to regulate BMSC activities has been developed. In this study, we have demonstrated a systematic approach to identify soluble factors of interest extracted from human bone marrow and used them in BMSC culture for tissue regeneration. We have found that lipocalin-2 and prolactin are key factors in bone marrow, involved in regulating BMSC activities. Treating the cell with lipocalin-2 and prolactin delays cellular senescence of BMSCs and primes the cell for osteogenesis and chondrogenesis. We have also demonstrated that BMSCs pretreated with lipocalin-2 and prolactin can enhance the repair of calvarial defects in mice. Together, our study provides research evidence of using a viable approach to prime BMSC properties in vitro for improving cell-based tissue regeneration in vivo.
Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53705, USA.
Tsung-Lin
TL
Tsai
Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53705, USA. Electronic address: li@ortho.wisc.edu.
Wan-Ju
WJ
Li
D001853:Bone Marrow / Q000378:metabolism*; D001861:Bone Regeneration / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D019070:Cell Lineage / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D016922:Cellular Senescence / Q000235:genetics; D020219:Chondrogenesis / Q000187:drug effects / Q000235:genetics; D017077:Culture Media, Conditioned; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016130:Immunophenotyping; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects; D010641:Phenotype; D023822:Tissue Engineering
D017077:Culture Media, Conditioned
bone marrow; bone regeneration; environmental cue; mesenchymal stem cells; soluble factors