Circulating plastic adherent mesenchymal stem cells in aged hip fracture patients

Orthopaedic Research Unit, Department of Orthopaedic Research and Traumatology, Turku University Hospital and University of Turku, Turku, Finland.
Journal of Orthopaedic Research (Impact Factor: 2.99). 12/2010; 28(12):1634-42. DOI: 10.1002/jor.21167
Source: PubMed


We examined the presence of circulating plastic adherent multipotent mesenchymal stem cells (MSCs) in fracture patients. Three patient groups (n = 10-18) were evaluated, including elderly females with a femoral neck fracture treated with cemented hemiarthroplasty, an age- and sex-matched group with hip osteoarthritis (OA) treated with cemented total hip arthroplasty (THA), and younger adults with surgically treated lower extremity fractures. The presence of circulating MSCs pre- and postoperatively was compared to bone marrow (BM) MSCs from the same subjects. Criteria for identifying MSCs included cell surface markers (CD105+, CD73+, CD90+, CD45-, CD14-), proliferation through several passages as well as osteogenic, chondrogenic, and adipogenic differentiation. Plastic adherent MSCs were found in peripheral blood (PB) from 22% of hip fracture patients, 46% of younger fracture patients, and in none of 63 pre- and postmenopausal women with hip OA. When detectable, circulating MSCs appeared between 39 and 101 h after fracture. PB derived MSCs did not differ from BM derived MSCs, except for a small population (<15%) of CD34+ cells among PB derived MSCs. This initial study indicates mobilization of MSCs into the circulation in response to fracture, even in very old patients, while circulating MSCs were not detectable before or after elective THA.

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Available from: Terhi J Heino, Oct 06, 2015
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    • "Furthermore, there are also good evidences that SDF-1a/CXCR4 play an important role in the mobilization of mesenchymal stem cells (MSCs) [7]. MSCs have been reported to promote repair of the remote tissue by mobilizing into peripheral blood by injury signals, and attract attention as donor cells for regenerative therapy [8]. "
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    ABSTRACT: Hypoxic-ischemic brain damage (HIBD) is a major cause of acute deaths and chronic nervous system damage. There is good evidence that stromal cell-derived factor-1 alpha (SDF-1α) has been receiving much interest in its role in the treatment of ischemic diseases. Here we aim to investigate the effect of intraperitoneal delivery of SDF-1α after experimental hypoxia-ischemia (HI) and the potentially involved mechanisms. A total of 129 mice were subjected to unilateral carotid artery ligation followed by 2.5 h of hypoxia, randomly assigned to three groups: sham, HI + vehicle and HI + SDF-1α. Mice treated with SDF-1α showed recovery of spatial learning abilities and pathological conditions, decreased number of apoptotic cells, and elevated expression of SDF-1α and its cognate receptor, CXC chemokine receptor-4 (CXCR4). Meanwhile, the increased number of mesenchymal stem cells (MSCs) was found in peripheral blood after SDF-1α treatment. Taken together, the treatment of SDF-1α after HIBD contributed to an improved functional recovery, and this behavioral restoration was paralleled by a reduction of apoptosis and mobilization of MSCs via SDF-1α/CXCR4. Copyright © 2015. Published by Elsevier Inc.
    Biochemical and Biophysical Research Communications 07/2015; 7(2). DOI:10.1016/j.bbrc.2015.06.135 · 2.30 Impact Factor
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    • "Upon sub-confluency, plastic-adherent MSCs were harvested using trypsin/EDTA and re-plated at 1000 cells/cm 2 . Criteria for identifying MSCs included phenotype (CD105+, CD73+, CD90+, CD45−, CD14−), proliferation through several passages, as well as osteogenic, chondrogenic, and adipogenic differentiation, as described earlier [17]. Cells at passage 2-5 were used for the exper- iments. "
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    ABSTRACT: Despite recent advances in bone tissue engineering, efficient bone formation and vascularization remains a challenge for clinical applications. The aim of this study was to investigate if the osteoblastic differentiation of human mesenchymal stromal cells (MSCs) can be enhanced by co-culturing them with peripheral blood (PB) mononuclear cells (MNCs), with and without vascular endothelial growth factor (VEGF), a coupling factor of bone formation and angiogenesis. Human bone marrow (BM) derived MSCs were co-cultured with PB-MNCs in osteogenic medium with or without VEGF. Osteoblastic differentiation and mineral deposition were studied by staining for alkaline phosphatase (ALP), and von Kossa, respectively, and measurements for ALP activity and calcium concentration (Ca). Cell proliferation was assayed with Alamar blue. The mechanism(s) were further studied by Transwell(®) cell culture experiments. Both ALP and mineralization (von Kossa and Ca) were significantly higher in the MSC-MNC co-cultures compared to plain MSC cultures. VEGF alone had no effect on osteoblastic differentiation of MSCs, but further enhanced differentiation in co-culture settings. The mechanism was shown to require cell-cell contact between MSCs and MNCs and the factors contributing to further differentiation appear to be soluble. No differences were observed in cell proliferation. Our study demonstrates that the in vitro ALP activity and mineralization of human BM-MSCs is more efficient in the presence of PB-MNCs, and exogenously added VEGF further enhances the stimulatory effect. This indicates that PB-MNCs could be a potential cell source in development of co-culture systems for novel tissue engineering applications for enhanced bone healing. Level IV. Experimental research study. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    Orthopaedics & Traumatology Surgery & Research 03/2015; 101(3). DOI:10.1016/j.otsr.2015.01.014 · 1.26 Impact Factor
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    • "Yang et al. demonstrated that engraftment of bone marrow-derived MSCs with gelatin beads successfully regenerated periodontal tissue in rats (Yang et al., 2010). Endogenous bone marrow-derived cells (BMCs) including MSCs have been reported to promote repair of the remote tissue by mobilizing into peripheral blood by injury signals, and homing to injured tissues (Mansilla et al., 2006; Alm et al., 2010). "
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    ABSTRACT: Bone marrow-derived cells (BMCs) are considered to be a major source of mesenchymal stem cells (MSCs) in adults and are known to be effective in periodontal tissue regeneration. However, whether endogenous BMCs are involved in periodontal tissue repair process is uncertain. We therefore created periodontal tissue defects in the buccal alveolar bone of mandibular first molars in bone marrow chimeric mice, and immunohistochemically examined the expression of stromal cell derived factor-1 (SDF-1) and the mobilization of BMCs. We found that SDF-1 expression was increased around the defects at as early as 1 week after injury and that BMCs were mobilized to the defects, while GFP+/CD45+ were rarely observed. Fluorescence-activated cell sorting (FACS) analysis demonstrated that the number of platelet-derived growth factor receptor (pdgfr) α+/Sca-1+ (PαS) cells in the bone marrow decreased after injury. Taken together, these results suggest that BMCs are mobilized to the periodontal tissue defects. Recruitment of BMCs, including a subset of MSCs could be a new target of periodontal treatment.
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