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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">sibmed</journal-id><journal-title-group><journal-title xml:lang="ru">Сибирский научный медицинский журнал</journal-title><trans-title-group xml:lang="en"><trans-title>Сибирский научный медицинский журнал</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2410-2512</issn><issn pub-type="epub">2410-2520</issn><publisher><publisher-name>ИЦиГ СО РАН</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.15372/SSMJ20200206</article-id><article-id custom-type="elpub" pub-id-type="custom">sibmed-372</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>МЕДИКО-БИОЛОГИЧЕСКИЕ НАУКИ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>BIOMEDICINE</subject></subj-group></article-categories><title-group><article-title>Безопасность применения кондиционной среды, полученной при направленной остеогенной индукции мезенхимальных стволовых клеток костного мозга крыс</article-title><trans-title-group xml:lang="en"><trans-title>The safety of the use of the conditioned medium obtained by directed osteogenic induction of rat bone marrow mesenchymal stem cells</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Покровская</surname><given-names>Л. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Pokrovskaya</surname><given-names>L. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Любовь Анатольевна Покровская</p><p>634050, г. Томск, просп. Ленина, 36</p></bio><bio xml:lang="en"><p>Lyubov’ A. Pokrovskaya</p><p>634050, Tomsk, Lenin av., 36</p></bio><email xlink:type="simple">pokrovskayal@ect-center.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6178-5329</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шерстобоев</surname><given-names>Е. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Sherstoboev</surname><given-names>E. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Евгений Юрьевич Шерстобоев, д.м.н., проф.</p><p>634050, г. Томск, просп. Ленина, 36634028, г. Томск, просп. Ленина, 3 </p></bio><bio xml:lang="en"><p>Evgeniy Yu. Sherstoboev, doctor of medical sciences, professor</p><p>634050, Tomsk, Lenin av., 36634028, Tomsk, Lenin av., 3 </p></bio><email xlink:type="simple">sherstoboev_eu@pharmso.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Надеждин</surname><given-names>С. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Nadezhdin</surname><given-names>S. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Сергей Викторович Надеждин, к.б.н.</p><p>308015, г. Белгород, ул. Победы, 85</p></bio><bio xml:lang="en"><p>Sergey V. Nadezhdin, candidate of biological sciences</p><p>308015, Belgorod, Pobedy str., 85</p></bio><email xlink:type="simple">sergey_nadezhdin@yahoo.com</email><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Данилец</surname><given-names>М. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Danilets</surname><given-names>M. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Марина Григорьевна Данилец, д.б.н.</p><p>634028, г. Томск, просп. Ленина, 3</p></bio><bio xml:lang="en"><p>Marina G. Danilets, doctor of biological sciences</p><p>634028, Tomsk, Lenin av., 3</p></bio><email xlink:type="simple">danilets_mg@pharmso.ru</email><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Трофимова</surname><given-names>Е. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Trofimova</surname><given-names>E. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Евгения Сергеевна Трофимова, к.м.н.</p><p>634028, г. Томск, просп. Ленина, 3</p></bio><bio xml:lang="en"><p>Evgeniya S. Trofimova, candidate of medical sciences</p><p>634028, Tomsk, Lenin av., 3</p></bio><email xlink:type="simple">eugenie76@mail.ru</email><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Лигачева</surname><given-names>А. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Ligacheva</surname><given-names>A. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Анастасия Александровна Лигачева, к.б.н.</p><p>634028, г. Томск, просп. Ленина, 3</p></bio><bio xml:lang="en"><p>Anastasiya A. Ligacheva, candidate of biological sciences</p><p>634028, Tomsk, Lenin av., 3</p></bio><email xlink:type="simple">vittelli@mail.ru</email><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Чурин</surname><given-names>А. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Churin</surname><given-names>A. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Алексей Александрович Чурин, д.м.н.</p><p>634028, г. Томск, просп. Ленина, 3</p></bio><bio xml:lang="en"><p>Aleksey A. Churin, doctor of medical sciences</p><p>634028, Tomsk, Lenin av., 3</p></bio><email xlink:type="simple">churin_aa@pharmso.ru</email><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Дубская</surname><given-names>Т. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Dubskaya</surname><given-names>T. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Татьяна Юрьевна Дубская, к.м.н.</p><p>634028, г. Томск, просп. Ленина, 3</p></bio><bio xml:lang="en"><p>Tat’yana Yu. Dubskaya, candidate of medical sciences</p><p>634028, Tomsk, Lenin av., 3</p></bio><email xlink:type="simple">tatatox@mail.ru</email><xref ref-type="aff" rid="aff-4"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Национальный исследовательский Томский государственный университет</institution><country>Россия</country></aff><aff xml:lang="en"><institution>National Research Tomsk State University</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Национальный исследовательский Томский государственный университет; НИИ фармакологии и регенеративной медицины имени Е.Д. Гольдберга, Томский национальный исследовательский медицинский центр РАН</institution><country>Россия</country></aff><aff xml:lang="en"><institution>National Research Tomsk State University; Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center of RAS</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>Белгородский государственный национальный исследовательский университет</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Belgorod National Research University</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-4"><aff xml:lang="ru"><institution>НИИ фармакологии и регенеративной медицины имени Е.Д. Гольдберга, Томский национальный исследовательский медицинский центр РАН</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center of RAS</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2020</year></pub-date><pub-date pub-type="epub"><day>02</day><month>05</month><year>2020</year></pub-date><volume>40</volume><issue>2</issue><fpage>47</fpage><lpage>55</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Покровская Л.А., Шерстобоев Е.Ю., Надеждин С.В., Данилец М.Г., Трофимова Е.С., Лигачева А.А., Чурин А.А., Дубская Т.Ю., 2020</copyright-statement><copyright-year>2020</copyright-year><copyright-holder xml:lang="ru">Покровская Л.А., Шерстобоев Е.Ю., Надеждин С.В., Данилец М.Г., Трофимова Е.С., Лигачева А.А., Чурин А.А., Дубская Т.Ю.</copyright-holder><copyright-holder xml:lang="en">Pokrovskaya L.A., Sherstoboev E.Y., Nadezhdin S.V., Danilets M.G., Trofimova E.S., Ligacheva A.A., Churin A.A., Dubskaya T.Y.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://sibmed.elpub.ru/jour/article/view/372">https://sibmed.elpub.ru/jour/article/view/372</self-uri><abstract><p>Цель исследования: изучить цитотоксичность in vitro и подострую токсичность in vivo кондиционной среды (КС), полученной при направленной остеогенной индукции мезенхимальных стволовых клеток (МСК) костного мозга крыс. Материал и методы. Кондиционную среду получали при культивировании МСК костного мозга крыс, индуцированных в остеогенном направлении. Результаты и их обсуждение. КС МСК костного мозга крыс, индуцированных в остеогенном направлении, не обладает существенным цитотоксическим действием на культуру клеток аденокарциномы Эрлиха и мононуклеары периферической крови здоровых доноров in vitro. Введение КС МСК не оказывало негативного влияния на состояние экспериментальных крыс SD, общую массу животных и ее прирост. Патоморфологическое исследование не выявило отклонений от общепринятой нормы, связанных с действием вводимого препарата. Заключение. Применение КС МСК костного мозга крыс, стимулированных в остеогенном направлении, как in vitro в отношении линии опухолевых клеток (аденокарцинома Эрлиха) и мононуклеаров периферической крови здоровых доноров, так и in vivo при введении экспериментальным животным является безопасным.</p></abstract><trans-abstract xml:lang="en"><p>The purpose of the study was to evaluate in vitro cytotoxicity and in vivo sub-acute toxicity of conditioned medium obtained from rat bone marrow-derived mesenchymal stem cells directed to osteogenic differentiation. Material and methods. Conditioned medium was obtained by culturing rat bone marrow-derived MSCs induced under osteogenic condition. Results and discussion. Conditioned medium from rat bone marrow-derived MSCs was shown to have no significant cytotoxic effect on Ehrlich adenocarcinoma cell culture and in vitro expanded peripheral blood mononuclear cells from healthy donors. The use of MSC-CM did not have a significant effect on the state of experimental SD rats, the total body weight and growth rate of animals. A pathomorphologic study revealed no any abnormalities associated with MSC-CM injection. Conclusion. The use of conditioned medium from rat bone marrow-derived mesenchymal stem cells stimulated under osteogenic condition was found to be safe for both in vitro studies (with respect to Ehrlich adenocarcinoma cell line and peripheral blood mononuclear cells from healthy donors) and in vivo studies (injection of MSC-CM to animals).</p></trans-abstract><kwd-group xml:lang="ru"><kwd>мезенхимальные стволовые клетки костного мозга крыс</kwd><kwd>кондиционная среда</kwd><kwd>цитотоксичность</kwd><kwd>подострая токсичность</kwd><kwd>крысы SD</kwd></kwd-group><kwd-group xml:lang="en"><kwd>rat bone marrow mesenchymal stem cells</kwd><kwd>conditioned medium</kwd><kwd>cytotoxicity</kwd><kwd>subacute toxicity</kwd><kwd>SD rats</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Исследование выполнено при финансовой поддержке Министерства науки и высшего образования РФ, соглашение № 14.575.21.0164, идентификатор RFMEFI57517X0164.</funding-statement><funding-statement xml:lang="en">The study was supported by the Ministry of Science and Higher Education of the Russian Federation, agreement No. 14.575.21.0164, identifier RFMEFI57517X0164.</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Athanasiou V.T., Papachristou D.J., Panagopoulos A., Saridis A., Scopa C.D., Megas P. Histological comparison of autograft, allograft-DBM, xenograft, and synthetic grafts in a trabecular bone defect: an experimental study in rabbits. Med. Sci. Monit. 2010; 16: 24–31.</mixed-citation><mixed-citation xml:lang="en">Athanasiou V.T., Papachristou D.J., Panagopoulos A., Saridis A., Scopa C.D., Megas P. Histological comparison of autograft, allograft-DBM, xenograft, and synthetic grafts in a trabecular bone defect: an experimental study in rabbits. Med. Sci. Monit. 2010; 16: 24–31.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Cantinieaux D., Quertainmont R., Blacher S., Rossi L., Wanet T., Noël A., Brook G., Schoenen J., Franzen R. Conditioned medium from bone marrow derived mesenchymal stem cells improves recovery after spinal cord injury in rats: an original strategy to avoid cell transplantation. PLoS One. 2013; 8: e69515, doi:10.1371/journal.pone.0069515</mixed-citation><mixed-citation xml:lang="en">Cantinieaux D., Quertainmont R., Blacher S., Rossi L., Wanet T., Noël A., Brook G., Schoenen J., Franzen R. Conditioned medium from bone marrow derived mesenchymal stem cells improves recovery after spinal cord injury in rats: an original strategy to avoid cell transplantation. PLoS One. 2013; 8: e69515, doi:10.1371/journal.pone.0069515</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Dawson J.I., Oreffo R.O. Bridging the regeneration gap: stem cells, biomaterials and clinical translation in bone tissue engineering. Arch. Biochem. Biophys. 2008; 473: 124–131. doi: 10.1016/j.abb.2008.03.024</mixed-citation><mixed-citation xml:lang="en">Dawson J.I., Oreffo R.O. Bridging the regeneration gap: stem cells, biomaterials and clinical translation in bone tissue engineering. Arch. Biochem. Biophys. 2008; 473: 124–131. doi: 10.1016/j.abb.2008.03.024</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Eppley B.L., Morales L., Wood R., Pensler J., Goldstein J., Havlik R.J., Habal M., Losken A., Williams J.K., Burstein F., Rozzelle A.A., Sadove A.M. Resorbable PLLA-PGA plate and screw fixation in pediatric craniofacial surgery: clinical experience in 1883 patients. Plast. Reconstr. Surg. 2004; 114: 850–856. doi: 10.1097/01.prs.0000132856.69391.43</mixed-citation><mixed-citation xml:lang="en">Eppley B.L., Morales L., Wood R., Pensler J., Goldstein J., Havlik R.J., Habal M., Losken A., Williams J.K., Burstein F., Rozzelle A.A., Sadove A.M. Resorbable PLLA-PGA plate and screw fixation in pediatric craniofacial surgery: clinical experience in 1883 patients. Plast. Reconstr. Surg. 2004; 114: 850–856. doi: 10.1097/01.prs.0000132856.69391.43</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Eppley B.L., Pietzak W.S., Blanton M.W. Allograft and alloplastic bone substitutes: a review of science and tеchnology for the craniomaxillofacial surgeon. J. Craniofac. Surg. 2005; 16: 981–989. doi:10.1097/01.scs.0000179662.38172.dd</mixed-citation><mixed-citation xml:lang="en">Eppley B.L., Pietzak W.S., Blanton M.W. Allograft and alloplastic bone substitutes: a review of science and tеchnology for the craniomaxillofacial surgeon. J. Craniofac. Surg. 2005; 16: 981–989. doi:10.1097/01.scs.0000179662.38172.dd</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Grayson W.L., Frohlich M., Yeager K., Bhumiratana S., Chan M.E., Cannizzaro C., Wan L.Q., Liu X.S., Guo X.E., Vunjak-Novakovic G. Engineering anatomically shaped human bone grafts. Proc. Natl. Acad. Sci. USA. 2010; 107: 3299–3304. doi: 10.1073/pnas.0905439106</mixed-citation><mixed-citation xml:lang="en">Grayson W.L., Frohlich M., Yeager K., Bhumiratana S., Chan M.E., Cannizzaro C., Wan L.Q., Liu X.S., Guo X.E., Vunjak-Novakovic G. Engineering anatomically shaped human bone grafts. Proc. Natl. Acad. Sci. USA. 2010; 107: 3299–3304. doi: 10.1073/pnas.0905439106</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Han Y., Li X., Zhang Y., Han Y., Chang F., Ding J. Mesenchymal stem cells for regenerative medicine. Cells. 2019; 13; 8 (8). doi: 10.1007/5584_2018_213</mixed-citation><mixed-citation xml:lang="en">Han Y., Li X., Zhang Y., Han Y., Chang F., Ding J. Mesenchymal stem cells for regenerative medicine. Cells. 2019; 13; 8 (8). doi: 10.1007/5584_2018_213</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Horie M., Choi H., Lee R.H., Reger R.L., Ylostalo J., Muneta T., Sekiya I., Prockop D.J. Intra-articular injection of human mesenchymal stem cells (MSCs) promote rat meniscal regeneration by being activated to express Indian hedgehog that enhances expression of type II collagen. Osteoarthritis Cartilage. 2012; 20: 1197–1207. doi: 10.1016/j.joca.2012.06.002</mixed-citation><mixed-citation xml:lang="en">Horie M., Choi H., Lee R.H., Reger R.L., Ylostalo J., Muneta T., Sekiya I., Prockop D.J. Intra-articular injection of human mesenchymal stem cells (MSCs) promote rat meniscal regeneration by being activated to express Indian hedgehog that enhances expression of type II collagen. Osteoarthritis Cartilage. 2012; 20: 1197–1207. doi: 10.1016/j.joca.2012.06.002</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Ide C., Nakai Y., Nakano N., Seo T.B., Yamada Y., Endo K., Noda T., Saito F., Suzuki Y., Fukushima M., Nakatani T. Bone marrow stromal cell transplantation for treatment of sub-acute spinal cord injury in rat. Brain Res. 2010; 1332: 32–47. doi: 10.1016/j.brainres.2010.03.043</mixed-citation><mixed-citation xml:lang="en">Ide C., Nakai Y., Nakano N., Seo T.B., Yamada Y., Endo K., Noda T., Saito F., Suzuki Y., Fukushima M., Nakatani T. Bone marrow stromal cell transplantation for treatment of sub-acute spinal cord injury in rat. Brain Res. 2010; 1332: 32–47. doi: 10.1016/j.brainres.2010.03.043</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Kay A.G., Long G., Tyler G., Stefan A., Broadfoot S.J., Piccinini A.M., Middleton J., Kehoe O. Mesenchymal stem cell-conditioned medium reduces disease severity and immune responses in inflammatory arthritis. Sci. Rep. 2017; 7: e18019. doi: 10.1038/s41598-017-18144-w</mixed-citation><mixed-citation xml:lang="en">Kay A.G., Long G., Tyler G., Stefan A., Broadfoot S.J., Piccinini A.M., Middleton J., Kehoe O. Mesenchymal stem cell-conditioned medium reduces disease severity and immune responses in inflammatory arthritis. Sci. Rep. 2017; 7: e18019. doi: 10.1038/s41598-017-18144-w</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Kinnaird T., Srabile E., Burnett M.S., Shou M., Lee C.W., Barr S., Fuchs S., Epstein S.E. Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation. 2004; 109: 1543–1549. doi: 10.1161/01.CIR.0000124062.31102.57</mixed-citation><mixed-citation xml:lang="en">Kinnaird T., Srabile E., Burnett M.S., Shou M., Lee C.W., Barr S., Fuchs S., Epstein S.E. Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation. 2004; 109: 1543–1549. doi: 10.1161/01.CIR.0000124062.31102.57</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Linero I., Chaparro O. Paracrine effect of mesenchymal stem cells derived from human adipose tissue in bone regeneration. PLoS One. 2014; 10: e107001, doi: 10.1371/journal.pone.0107001</mixed-citation><mixed-citation xml:lang="en">Linero I., Chaparro O. Paracrine effect of mesenchymal stem cells derived from human adipose tissue in bone regeneration. PLoS One. 2014; 10: e107001, doi: 10.1371/journal.pone.0107001</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Minenna L., Herrero F., Sanz M., Trombelli L. Adjunctive effect of a polylactide/polyglycolide copolymer in the treatment of deep periodontal intraosseous defects: a randomized clinical trial. J. Clin. Periodontol. 2005; 32: 456–461. doi: 10.1111/j.1600051X.2005.00696.x</mixed-citation><mixed-citation xml:lang="en">Minenna L., Herrero F., Sanz M., Trombelli L. Adjunctive effect of a polylactide/polyglycolide copolymer in the treatment of deep periodontal intraosseous defects: a randomized clinical trial. J. Clin. Periodontol. 2005; 32: 456–461. doi: 10.1111/j.1600051X.2005.00696.x</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Patel D.M., Shah J., Srivastava A.S. Therapeutic potential of mesenchymal stem cells in regenerative medicine. Stem. Cells Int. 2013; 2013: 496218. doi: 10.1155/2013/496218</mixed-citation><mixed-citation xml:lang="en">Patel D.M., Shah J., Srivastava A.S. Therapeutic potential of mesenchymal stem cells in regenerative medicine. Stem. Cells Int. 2013; 2013: 496218. doi: 10.1155/2013/496218</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Pawitan J.A. Prospect of stem cell conditioned medium in regenerative medicine. BioMed. Res. Int. 2014; 2014: 1–14. doi: 10.1155/2014/965849</mixed-citation><mixed-citation xml:lang="en">Pawitan J.A. Prospect of stem cell conditioned medium in regenerative medicine. BioMed. Res. Int. 2014; 2014: 1–14. doi: 10.1155/2014/965849</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Perez J.R., Kouroupis D., Li D.J., Best T.M., Kaplan L., Correa D. Tissue Engineering and CellBased Therapies for Fractures and Bone Defects. Front. Bioeng. Biotechnol. 2018; 6: 105. doi: 10.3389/fbioe.2018.00105</mixed-citation><mixed-citation xml:lang="en">Perez J.R., Kouroupis D., Li D.J., Best T.M., Kaplan L., Correa D. Tissue Engineering and CellBased Therapies for Fractures and Bone Defects. Front. Bioeng. Biotechnol. 2018; 6: 105. doi: 10.3389/fbioe.2018.00105</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Perri B., Cooper M., Lauryssen C., Anand N. Adverse swelling associated with use of rh-BMP-2 in anterior cervical discectomy and fusion: a case study. Spine J. 2007; 7: 235–239. doi: 10.1016/j.spinee.2006.04.010</mixed-citation><mixed-citation xml:lang="en">Perri B., Cooper M., Lauryssen C., Anand N. Adverse swelling associated with use of rh-BMP-2 in anterior cervical discectomy and fusion: a case study. Spine J. 2007; 7: 235–239. doi: 10.1016/j.spinee.2006.04.010</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Peter S.J., Liang C.R., Kim D.J., Widmer M.S., Mikos A.G. Osteoblastic phenotype of rat marrow stromal cells cultured in the presence of dexamethasone, beta-glycerolphosphate, and L-ascorbic acid. J. Cell Biochem. 1998; 71: 55–62. doi: 10.1002/(sici)10974644(19981001)71:1&lt;55::aid-jcb6&gt;3.0.co;2-0</mixed-citation><mixed-citation xml:lang="en">Peter S.J., Liang C.R., Kim D.J., Widmer M.S., Mikos A.G. Osteoblastic phenotype of rat marrow stromal cells cultured in the presence of dexamethasone, beta-glycerolphosphate, and L-ascorbic acid. J. Cell Biochem. 1998; 71: 55–62. doi: 10.1002/(sici)10974644(19981001)71:1&lt;55::aid-jcb6&gt;3.0.co;2-0</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Pittenger M.F., Mbalaviele G., Black M., Mosca J.D., Marshak D.R. Mesenchymal Stem Cells. In: Human cell culture. Eds. M.R. Koller, B.O. Palsson, J.R.W. Masters. Dordrecht: Springer, 2001. Vol. 5: 189–207. doi: 10.1007/0-306-46870-0_9</mixed-citation><mixed-citation xml:lang="en">Pittenger M.F., Mbalaviele G., Black M., Mosca J.D., Marshak D.R. Mesenchymal Stem Cells. In: Human cell culture. Eds. M.R. Koller, B.O. Palsson, J.R.W. Masters. Dordrecht: Springer, 2001. Vol. 5: 189–207. doi: 10.1007/0-306-46870-0_9</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Sanchooli T., Norouzian M., Ardeshirylajimi A., Ghoreish S.K., Abdollahifar M.A., Nazarian H., Piryaei A. Adipose derived stem cells conditioned media in combination with bioceramic collagen scaffolds improved calvarial bone healing in hypothyroid rats. Iran. Red. Crescent. Med. J. 2017; 19: e45516. doi: 10.5812/ircmj.45516</mixed-citation><mixed-citation xml:lang="en">Sanchooli T., Norouzian M., Ardeshirylajimi A., Ghoreish S.K., Abdollahifar M.A., Nazarian H., Piryaei A. Adipose derived stem cells conditioned media in combination with bioceramic collagen scaffolds improved calvarial bone healing in hypothyroid rats. Iran. Red. Crescent. Med. J. 2017; 19: e45516. doi: 10.5812/ircmj.45516</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Song I.H., Caplan A.I., Dennis J.E. In vitro dexamethasone pretreatment enhances bone formation of human mesenchymal stem cells in vivo. J. Orthop. Res. 2009; 27: 916–921. doi: 10.1002/jor.20838</mixed-citation><mixed-citation xml:lang="en">Song I.H., Caplan A.I., Dennis J.E. In vitro dexamethasone pretreatment enhances bone formation of human mesenchymal stem cells in vivo. J. Orthop. Res. 2009; 27: 916–921. doi: 10.1002/jor.20838</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Um S., Kim H.Y., Seo B.M. Effects of BMP-2 on the osteogenic differentiation of bone marrow stem cells in fibrous dysplasia. Oral. Dis. 2018; 6: 10571067. doi: 10.1111/odi.12869</mixed-citation><mixed-citation xml:lang="en">Um S., Kim H.Y., Seo B.M. Effects of BMP-2 on the osteogenic differentiation of bone marrow stem cells in fibrous dysplasia. Oral. Dis. 2018; 6: 10571067. doi: 10.1111/odi.12869</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Visser R., Rico-Llanos G.A., Pulkkinen H., Becerra J. Peptides for bone tissue engineering. J. Controlled Release. 2016; 244: 122–135. doi: 10.1016/j.jconrel.2016.10.024</mixed-citation><mixed-citation xml:lang="en">Visser R., Rico-Llanos G.A., Pulkkinen H., Becerra J. Peptides for bone tissue engineering. J. Controlled Release. 2016; 244: 122–135. doi: 10.1016/j.jconrel.2016.10.024</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Yun Y.R., Jang J.H., Jeon E., Kang W., Lee S., Won J.E., Kim H.W., Wall I. Administration of growth factors for bone regeneration. Regen. Med. 2012; 7: 369–385. doi: 10.2217/rme.12.1</mixed-citation><mixed-citation xml:lang="en">Yun Y.R., Jang J.H., Jeon E., Kang W., Lee S., Won J.E., Kim H.W., Wall I. Administration of growth factors for bone regeneration. Regen. Med. 2012; 7: 369–385. doi: 10.2217/rme.12.1</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
