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  • Wiley  (2)
  • Ohta, Souichi  (2)
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  • Wiley  (2)
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  • 1
    In: Microsurgery, Wiley, Vol. 37, No. 6 ( 2017-09), p. 632-640
    Abstract: Recent studies have indicated that bone marrow‐derived stromal cells (BMSCs) have immunomodulatory properties that suppress the T cell responses that cause graft rejection. The purpose of this study is to evaluate the effect of recipient BMSCs intravenous infusion for immunomodulation in a rat vascularized composite allotransplantation model. Methods A total of nine Wistar (WIS) rats and thirty Lewis (LEW) rats were used. BMSCs were harvested from three LEW rats. Twenty‐four LEW rats were used as recipients and divided randomly into four groups: BMSC group, FK group, UT group, and Iso group. In the BMSC group, orthotopic rat hind limb transplantation was performed between WIS donor and LEW recipient rats. Recipient rats were injected intravenously with 2 × 10 6 recipient BMSCs on day 6, and with 0.2 mg/kg/day tacrolimus administered over 7 days ( n  = 6). In the FK group, recipient rats were treated with tacrolimus alone ( n  = 6). Rats in the UT group received no immunosuppressive treatment ( n  = 6). In the Iso group, transplantation was performed from three LEW donor rats to six LEW recipient rats without any immunosuppressive treatment ( n  = 6). Graft survival was assessed by daily inspection and histology. The immunological reactions of recipients were also evaluated. Results The graft survival of recipient rats in the BMSC group (24.5 days) was significantly prolonged in comparison with that of the FK group (18 days) ( P   〈  .01). Cytokine expression analysis of the skin of grafted limbs showed that BMSCs treatment significantly decreased IFN‐γ mRNA expression of the BMSC group (0.138 ± 0.045) in comparison with that of the FK group (1.049 ± 0.167) ( P  = .0001). Recipient rats in the BMSC group had significantly reduced serum IFN‐γ cytokine levels (1.571 ± 0.779 pg/ml) in comparison with that of the FK group (7.059 ± 1.522 pg/ml) ( P  = .001). In in vitro study, BMSCs induce T cell hyporesponsiveness in a mixed lymphocyte reaction. Conclusion BMSCs induce T cell hyporesponsiveness and prolong graft survival in the rat vascularized composite allotransplantation model. BMSCs exhibit immunomodulatory properties against acute rejection that can be realized without the need for significant recipient immunosuppression.
    Type of Medium: Online Resource
    ISSN: 0738-1085 , 1098-2752
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 1475571-3
    detail.hit.zdb_id: 605524-2
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  • 2
    In: Microsurgery, Wiley, Vol. 36, No. 4 ( 2016-05), p. 316-324
    Abstract: Previously, we showed that undifferentiated bone marrow stromal cell (uBMSC) implantation and vessel insertion into a nerve conduit facilitated peripheral nerve regeneration in a rodent model. In this study, we investigated the efficacy of the uBMSC‐laden vessel‐containing conduit in repair of segmental nerve defects, using a canine model. Eight beagle dogs were used in this study. Thirty‐millimeter ulnar nerve defects were repaired with the conduits (right forelimbs, n  = 8) or autografts (left forelimbs, n  = 7). In the conduit group, the ulnar artery was inserted into the l‐lactide/ε‐caprolactone tube, which was filled with autologous uBMSCs obtained from the ilium. In the autograft group, the reversed nerve segments were sutured in situ. At 8 weeks, one dog with only nerve repair with the conduit was sacrificed and the regenerated nerve in the conduit underwent immunohistochemistry for investigation of the differentiation capability of the implanted uBMSCs. In the remaining seven dogs, the repaired nerves underwent electrophysiological examination at 12 and 24 weeks and morphometric measurements at 24 weeks. The wet weight of hypothenar muscles was measured at 24 weeks. At 8 weeks, almost 35% of the implanted uBMSCs expressed glial markers. At 12 weeks, amplitude (0.4 ± 0.4mV) and conduction velocity (18.9 ± 14.3m/s) were significantly lower in the conduit group than in the autograft group (3.2 ± 2.5 mV, 34.9 ± 12.1 m/s, P   〈  0.05). Although the nerve regeneration in the conduit group was inferior when compared with the autograft group at 24 weeks, there were no significant differences between both groups, regarding amplitude (10.9 ± 7.3 vs. 25.3 ± 20.1 mV; P  = 0.11), conduction velocity (23.5 ± 8.7 vs 31.6 ± 20.0m/s; P  = 0.35), myelinated axon number (7032 ± 4188 vs 7165 ± 1814; P  = 0.94), diameter (1.73 ± 0.31 vs 2.09 ± 0.39μm; P  = 0.09), or muscle weight (1.02 ± 0.40 vs 1.19 ± 0.26g; P  = 0.36). In conclusion, this study showed that vessel‐containing tubes with uBMSC implantation may be an option for treatment of peripheral nerve injuries. However, further investigations are needed. © 2015 Wiley Periodicals, Inc. Microsurgery 36:316–324, 2016.
    Type of Medium: Online Resource
    ISSN: 0738-1085 , 1098-2752
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 1475571-3
    detail.hit.zdb_id: 605524-2
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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