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Introduction: Whartons Jelly stem cells(WJSCs)have been used as alternative to bone marrow derived mesenchymal stem cells(BMMSCs).We investigated the population of MSCs derived from different segments of human umbilical cord-the maternal,middle and fetal segments.MSCs were successfully expanded from three centimetre-long segment.MSCs from maternal and fetal segments were preferred in terms of their growth profile,cell viability,pluripotent embryonic markers expression,and higher osteogenic potential in vitro compared to those derived from the middle segment.We proceeded to form tissue engineered bone constructs using osteo-differentiated MSCs from maternal and fetal segments.We then investigated the safety and efficacy of transplanting these xenogenic bone constructs in immunocompetent mice(BALB/C).Methods: Animals were divided into 4 groups(control,maternal,fetal and fibrin group).3D bone construct were formed with human fibrin and WJSCs from maternal and fetal segments.After one month of implantation,mice were euthanized.Bone constructs,lymphoid organs were harvested,fixed and stained with haematoxylin and eosin.Serum samples were obtained for inflammatory markers detection.Results & Discussion: Mineralized bones were found in constructs of all except the fibrin group.Xenogenic fibrin had triggered an acute reaction evident by the enlargement of thymus and spleen in fibrin group.Maternal group showed the least immunogenic response based on the minimal changes seen in lymphoid organs.Pro-inflammatory cytokines(MMP-3,ICAM-1,galectin-3,fractakine,TNFα,IFNγ,IL-3,IL-6 and IL-1α)were highest in fibrin group.Anti-inflammatory cytokines(HGF,galectin-1,IL-13 and IL-10)were upregulated in fetal and maternal groups.Conclusion: Xenogenic WJSCs from maternal and fetal segments have the ability to suppress acute reaction toward fibrin.Bone constructs using WJMSCs from maternal segments are safe to be used allogenically for bone regeneration.These results were consistent with our previous findings in lymphocyte proliferation assay in vitro.