A unique heterologous fibrin sealant (HFS) as a candidate biological scaffold for mesenchymal stem cells in osteoporotic rats

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dc.contributor.authorOrsi, Patrícia Rodrigues [UNESP]
dc.contributor.authorLandim-Alvarenga, Fernanda Cruz [UNESP]
dc.contributor.authorJustulin, Luis Antônio [UNESP]
dc.contributor.authorKaneno, Ramon [UNESP]
dc.contributor.authorDe Assis Golim, Marjorie [UNESP]
dc.contributor.authorDos Santos, Daniela Carvalho [UNESP]
dc.contributor.authorCreste, Camila Fernanda Zorzella [UNESP]
dc.contributor.authorOba, Eunice [UNESP]
dc.contributor.authorMaia, Leandro [UNESP]
dc.contributor.authorBarraviera, Benedito [UNESP]
dc.contributor.authorFerreira, Rui Seabra [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2018-12-11T17:15:04Z
dc.date.available2018-12-11T17:15:04Z
dc.date.issued2017-09-29
dc.description.abstractBackground: The injection of mesenchymal stem cells (MSCs) directly into the bone of osteoporotic (OP) patients for rapid recovery has been studied worldwide. Scaffolds associated with MSCs are used to maintain and avoid cell loss after application. A unique heterologous fibrin sealant (HFS) derived from snake venom was evaluated for the cytotoxicity of its main components and as a three-dimensional biological scaffold for MSCs to repair a critical femur defect in osteoporotic rats. Methods: The cytotoxicity of HFS was assessed using a 3-(4,5-dimethyl-2-Thiazolyl)-2,5-diphenyl-2H-Tetrazoliumbromide (MTT) assay and transmission electron microscopy. The cells were cultured, characterized by flow cytometry and differentiated into the osteogenic lineage. Two-month-old rats underwent ovariectomy to induce OP. After 3 months, a 5 mm critical bone defect was made in the distal end of the rat femurs and filled with HFS; HFS + MSCs; and HFS + MSCs D (differentiated into the osteogenic lineage) to evaluate the effects. An injury control group (injury and no treatment) and blank control group (no injury and no treatment) were also included. The animals were observed at days 14 and 28 by microtomographic (micro-CT) analyses, histologic and biochemical analysis, as well as scanning electron microscopy. Results: The results revealed that one of the compounds of HFS, the thrombin-like enzyme extracted from snake venom, had no cytotoxic effects on the MSCs. OP was successfully induced, as demonstrated by the significant differences in the levels of 17β-estradiol, Micro-CT analyses and alkaline phosphatase between the ovariectomized (OVX) and non-ovariectomized (NOVX) groups. The histological data revealed that at 14 days after surgery in both the OVX and NOVX animals, the HFS + CTMs and HFS + CTMsD showed a higher formation of bone cells at the site in relation to the control group (without treatment). Collagen formation was evidenced through bone neoformation in all treated and control groups. No morphological differences in the femurs of the NOVX and OVX animals were observed after the surgical procedure. Scanning electron microscopy (SEM) confirmed the histological analysis. Conclusions: The new HFS composed of two non-Toxic components for MSCs showed capacity to promote the recovery of the bone lesions in OVX and NOVX animals at 14 days after surgery. In addition, the HFS enabled the differentiation of MSCs into MSCs D in the group treated with HFS + MSCs. Using the MSCs and/or MSCs D together with this biopharmaceutical could potentially enable significant advances in the treatment of osteoporotic fractures. Future clinical trials will be necessary to confirm these results.en
dc.description.affiliationCenter for the Study of Venoms and Venomous Animals (CEVAP) UNESP-Universidade Estadual Paulista
dc.description.affiliationBotucatu Medical School UNESP-Universidade Estadual Paulista
dc.description.affiliationBotucatu Biosciences Institute UNESP-Universidade Estadual Paulista
dc.description.affiliationCollege of Veterinary Medicine and Animal Husbandry (FMVZ) UNESP-Univ Estadual Paulista
dc.description.affiliationUnespCenter for the Study of Venoms and Venomous Animals (CEVAP) UNESP-Universidade Estadual Paulista
dc.description.affiliationUnespBotucatu Medical School UNESP-Universidade Estadual Paulista
dc.description.affiliationUnespBotucatu Biosciences Institute UNESP-Universidade Estadual Paulista
dc.description.affiliationUnespCollege of Veterinary Medicine and Animal Husbandry (FMVZ) UNESP-Univ Estadual Paulista
dc.identifierhttp://dx.doi.org/10.1186/s13287-017-0654-7
dc.identifier.citationStem Cell Research and Therapy, v. 8, n. 1, 2017.
dc.identifier.doi10.1186/s13287-017-0654-7
dc.identifier.file2-s2.0-85030156974.pdf
dc.identifier.issn1757-6512
dc.identifier.lattes8456490300814833
dc.identifier.lattes8845835550637809
dc.identifier.orcid0000-0002-2420-2550
dc.identifier.orcid0000-0002-4292-3298
dc.identifier.scopus2-s2.0-85030156974
dc.identifier.urihttp://hdl.handle.net/11449/175270
dc.language.isoeng
dc.relation.ispartofStem Cell Research and Therapy
dc.relation.ispartofsjr1,685
dc.rights.accessRightsAcesso aberto
dc.sourceScopus
dc.subjectCytotoxicity
dc.subjectFibrin sealant
dc.subjectFibrinogen
dc.subjectOsteoporosis
dc.subjectSnake venom
dc.titleA unique heterologous fibrin sealant (HFS) as a candidate biological scaffold for mesenchymal stem cells in osteoporotic ratsen
dc.typeArtigo
unesp.author.lattes6840524602748457[10]
unesp.author.lattes8456490300814833[2]
unesp.author.lattes8845835550637809[4]
unesp.author.orcid0000-0002-9855-5594[10]
unesp.author.orcid0000-0002-2420-2550[2]
unesp.author.orcid0000-0002-4292-3298[4]

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Botucatu - CEVAP - Centro de Estudos de Venenos e Animais Peçonhentos