vestibИзвестия Национальной академии наук Беларуси. Серия биологических наукProceedings of the National Academy of Sciences of Belarus, Biological Series1029-89402524-230XThe Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1029-8940-2022-67-3-309-320vestib-824Research ArticleОБЗОРЫREVIEWSТранскрипционные факторы ‒ ключевые регуляторные биомолекулы, определяющие направление дифференцировки мезенхимальных стволовых клеток в соматические клетки органов и тканейTranscription factors – key regulatory biomolecules determining the differentiation of mesenchimal stem cells into the somatic cells of organs and tissuesВолотовскийИ. Д.VolotovskiI. D.

Волотовский Игорь Дмитриевич ‒ академик, д-р биол. наук, профессор, гл. науч. сотрудник

ул. Академическая, 27, 220072, г. Минск

Igor D. Volotovski ‒ Academician, D. Sc. (Biol.), Professor, Сhief Researcher

27, Akademicheskaya Str., 220072, Minsk

volotovski@yahoo.comПинчукС. В.PinchukS. V.

Пинчук Сергей Владимирович ‒ канд. биол. наук, вед. науч. сотрудник

ул. Академическая, 27, 220072, г. Минск

Sergei V. Pinchuk ‒ Ph. D. (Biol.), Leading Researche

27, Akademicheskaya Str., 220072, Minsk

pinchuksv@mail.ruВасилевичИ. Б.VasilevichI. B.

Василевич Ирина Борисовна ‒ науч. сотрудник

ул. Академическая, 27, 220072, г. Минск

Irina B. Vasilevich ‒ Researcher

27, Akademicheskaya Str., 220072, Minsk

 

irina-vasilevich@yandex.ruИнститут биофизики и клеточной инженерии НАН БеларусиInstitute of Biophysics and Cell Engineering of the National Academy of Sciences of Belarus202204082022673309320Copyright © Волотовский И.Д., Пинчук С.В., Василевич И.Б., 20222022Волотовский И.Д., Пинчук С.В., Василевич И.Б.Volotovski I.D., Pinchuk S.V., Vasilevich I.B.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestibio.belnauka.by/jour/article/view/824

В статье рассматриваются механизмы дифференцировки мезенхимальных стволовых клеток в соматические клетки органов и тканей, лежащие в основе эмбриогенеза и естественных репаративных процессов в клетке и поддерживающие структурный и функциональный гомеостаз клеточного пула в разрезе целостного организма, что тем самым определяет судьбу индивидуальных клеток. Приводятся данные об адипогенной, остеогенной, хондрогенной, миогенной и эндотелиальной дифференцировках, приводящих к формированию в организме системных клеток мезодермального происхождения. Рассматривается также вопрос о том, каким образом осуществляется контроль каждого из видов диффереренцировки и участие в них разнообразных регуляторных биомолекул, транскрипционных факторов, цитокинов и химокинов, находящихся в постоянном cложном взаимодействии друг с другом и образующих в клетке интегральную регуляторную сеть. Обсуждается участие в процессах дифференцировки ряда траскрипционых факторов (Runx2, Sox9, PPARγ, MyoD, GATA4 и GATA6), экспрессия которых находится под постоянным химическим контролем в пределах регуляторной сети клетки.

Тhe mechanisms of differentiation of mesenchimal stem cells into the somatic cells of organs and tissues underlying embryogenesis and natural reparation processes and providing the structural and functional homeostasis of cells are considered. The data on adipogenic, osteogenic, chondrogenic, miogenic, and endothelial differentiations are given, which results in the formation of the cells of mesodermal origin in organism. The problem is discussed, how the transcription factors control each type of differentiation and participatе in them using various regulatory biomolecules, transcription factors, cytokines, and chimokins being in complicate permanent interactions and forming the integrity regulatory network. The participation in differentiation processes of a number of transcription factors (Runx2, Sox9, PPARγ, MyoD, GATA4 и GATA6) is discussed, the expression of which is under a permanent chemical control within the cellular regulatory network.

мезенхимальные стволовые клеткидифференцировкатранскрипционные факторысоматические клетки органов и тканейэмбриогенезрегуляторные сетирегенеративные процессыmesenchimal stem cellsdifferentiationtranscription factorssomatic cells of organs and tissuesembryogenesisregulatory networksregenerative processesReferencesOrigin of bone marrow stromal mechanocytes in radiochimeras and heterotopic transplants / A. J. Friedenstein [et al.] // Exp. Hematol. – 1978. – Vol. 6, N 5. – P. 440–444.Friedenstein A. J., Ivanov-Smolenski A. A., Chajlakjan A. R., Gorskaya U. F., Kuralesova A. I., Latzinik N. W., Gerasimov U.W. Origin of bone marrow stromal mechanocytes in radiochimeras and heterotopic transplants. Experimental Hematology, 1978, vol. 6, no. 5, pp. 440–444.Caplan, A. I. Mesenchymal stem cells: building blocks for molecular medicine in the 21st century / A. I. Caplan, S. P. Bruder // Trends Mol. Med. – 2001. – Vol. 7, N 6. – P. 259–264. https://doi.org/10.1016/S1471-4914(01)02016-0Caplan A. I., Bruder S. P. Mesenchymal stem cells: building blocks for molecular medicine in the 21st century. Trends in Molecular Medicine, 2001, vol. 7, no. 6, pp. 259–264. https://doi.org/10.1016/S1471-4914(01)02016-0Herzog, E. L. Plasticity of marrow-derived stem cells / E. L. Herzog, L. Chai, D. S. Krause // Blood. – 2003. – Vol. 102, N 10. – P. 3483–3493. https://doi.org/10.1182/blood-2003-05-1664Herzog E. L., Chai L., Krause D. S. Plasticity of marrow-derived stem cells. Blood, 2003, vol. 102, no. 10, pp. 3483–3493. https://doi.org/10.1182/blood-2003-05-1664Prockop, D. J. Repair of tissues by adult stem/progenitor cells (MSCs): controversies, myths, and changing paradigms / D. J. Prockop // Mol. Ther. – 2009. – Vol. 17, N 6. – P. 939–946. https://doi.org/10.1038/mt.2009.62Prockop D. J. Repair of tissues by adult stem/progenitor cells (MSCs): controversies, myths, and changing paradigms. Molecular Therapy, 2009, vol. 17, no. 6, pp. 939–946. https://doi.org/10.1038/mt.2009.62Chen, S. L. Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction / S.-L. Chen [et al.] // Am. J. Cardiol. – 2004. – Vol. 94, N 1. – P. 92–95. https://doi.org/10.1016/j.amjcard.2004.03.034Chen S.-L., Fang W.-W., Ye F., Liu Y.-H., Qian J., Shan S.-J. [et al.]. Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction. American Journal of Cardiology, 2004, vol. 94, no. 1, pp. 92–95. https://doi.org/10.1016/j.amjcard.2004.03.034le Blanc, K. Immunobiology of human mesenchymal stem cells and future use in hematopoietic stem cell transplantation / K. le Blanc, O. Ringden // Biol. Blood Marrow Transplant. – 2005. – Vol. 11, N 5. – P. 321–334. https://doi.org/10.1016/j.bbmt.2005.01.005Le Blanc K., Ringden O. Immunobiology of human mesenchymal stem cells and future use in hematopoietic stem cell transplantation. Biology of Blood and Marrow Transplantation, 2005, vol. 11, no. 5, pp. 321–334. https://doi.org/10.1016/j.bbmt.2005.01.005A perivascular origin for mesenchymal stem cells in multiple human organs / M. Crisan [et al.] // Cell Stem Cell. – 2008. – Vol. 3, N 3. – P. 301–313. https://doi.org/10.1016/j.stem.2008.07.003Crisan M., Yap S., Casteilla L., Chen C. W., Corselli M., Park T. S. [et al.]. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell, 2008, vol. 3, no. 3, pp. 301–313. https://doi.org/10.1016/j.stem.2008.07.003Almalki, S. G. Key transcription factors in the differentiation of mesenchymal stem cells / S. G. Almalki, D. K. Agrawal // Differentiation. – 2016. – Vol. 92, N 1–2. – P. 41–51. https://doi.org/10.1016/j.diff.2016.02.005Almalki S. G., Agrawal D. K. Key transcription factors in the differentiation of mesenchymal stem cells. Differentiation, 2016, vol. 92, no. 1–2, pp. 41–51. https://doi.org/10.1016/j.diff.2016.02.005Friedenstein, A. J. Bone marrow osteogenic stem cells: in vitro cultivation and transplantation in diffusion chambers / A. J. Friedenstein, R. K. Chailakhyan, U. V. Gerasimov // Cell Tissue Kinet. – 1987. – Vol. 20, N 3. – P. 263–272. https://doi.org/10.1111/j.1365-2184.1987.tb01309.xFriedenstein A. J., Chailakhyan R. K., Gerasimov U. V. Bone marrow osteogenic stem cells: in vitro cultivation and transplantation in diffusion chambers. Cell and Tissue Kinetics, 1987, vol. 20, no. 3, pp. 263–272. https://doi.org/10.1111/j.1365-2184.1987.tb01309.xAugello, A. The regulation of differentiation in mesenchymal stem cells / A. Augello, C. de Bari // Hum. Gene Ther. – 2010. – Vol. 21, N 10. – P. 1226–1238. https://doi.org/10.1089/hum.2010.173Augello A., de Bari C. The regulation of differentiation in mesenchymal stem cells. Human Gene Therapy, 2010, vol. 21, no. 10, pp. 1226–1238. https://doi.org/10.1089/hum.2010.173Clonal heterogeneity in differentiation potential of immortalized human mesenchymal stem cells / T. Okamoto [et al.] // Biochem. Biophys. Res. Commun. – 2002. – Vol. 295, N 2. – P. 354–361. https://doi.org/10.1016/S0006-291X(02)00661-7Okamoto T., Aoyama T., Nakayama T., Nakamata T., Hosaka T., Nishijo K., Nakamura T., Kiyono T., Toguchida J. Clonal heterogeneity in differentiation potential of immortalized human mesenchymal stem cells. Biochemical and Biophysical Research Communications, 2002, vol. 295, no. 2, pp. 354–361. https://doi.org/10.1016/S0006-291X(02)00661-7Delivery of the Sox9 gene promotes chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells in an in vitro model / Z. H. Wang [et al.] // Braz. J. Med. Biol. Res. – 2014. – Vol. 47, N 4. – P. 279–286. https://doi.org/10.1590/1414-431X20133539Wang Z. H., Li X. L., He X. J., Wu B. J., Xu M., Chang H. M. [et al.]. Delivery of the Sox9 gene promotes chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells in an in vitro model. Brazilian Journal of Medical and Biological Research, 2014, vol. 47, no. 4, pp. 279–286. https://doi.org/10.1590/1414-431X20133539Chondrogenesis of human mesenchymal stem cells mediated by the combination of SOX trio SOX5, 6, and 9 genes complexed with PEI-modified PLGA nanoparticles / J. S. Park [et al.] // Biomaterials. – 2011. – Vol. 32, N 14. – P. 3679–3688. https://doi.org/10.1016/j.biomaterials.2011.01.063Park J. S., Yang H. N., Woo D. G., Jeon S. Y., Do H. J., Lim H. Y., Kim J. H., Park K. H. Chondrogenesis of human mesenchymal stem cells mediated by the combination of SOX trio SOX5, 6, and 9 genes complexed with PEI-modified PLGA nanoparticles. Biomaterials, 2011, vol. 32, no. 14, pp. 3679–3688. https://doi.org/10.1016/j.biomaterials.2011.01.063Role of Hox genes in stem cell differentiation / A. Seifert [et al.] // World J. Stem Cells. – 2015. – Vol. 7, N 3. – P. 583–595. https://dx.doi.org/10.4252/wjsc.v7.i3.583Seifert A., Werheid D. F., Knapp S. M., Tobiasch E. Role of Hox genes in stem cell differentiation. World Journal of Stem Cells, 2015, vol. 7, no. 3, pp. 583–595. https://doi.org/10.4252/wjsc.v7.i3.583Yes-associated protein (YAP) is a negative regulator of chondrogenesis in mesenchymal stem cells / A. Karystinou [et al.] // Arthritis Res. Ther. – 2015. – Vol. 17, N 1. – P. 147. https://doi.org 10.1186/s13075-015-0639-9Karystinou A., Roelofs A. J., Neve A., Cantatore F. P, Wackerhage H., de Bari C. Yes-associated protein (YAP) is a negative regulator of chondrogenesis in mesenchymal stem cells. Arthritis Research and Therapy, 2015, vol. 17, no. 1, p. 147. https://doi.org/10.1186/s13075-015-0639-9Contribution of the interleukin-6/STAT-3 signaling pathway to chondrogenic differentiation of human mesenchymal stem cells / M. Kondo [et al.] // Arthritis Rheumatol. – 2015. – Vol. 67, N 5. – P. 1250–1260. https://doi.org.10.1002/art.39036Kondo M., Yamaoka K., Sakata K., Sonomoto K., Lin L., Nakano K., Tanaka Y. Contribution of the interleukin-6/ STAT-3 signaling pathway to chondrogenic differentiation of human mesenchymal stem cells. Arthritis and Rheumatology, 2015, vol. 67, no. 5, pp. 1250–1260. https://doi.org/10.1002/art.39036Insulin stimulates adipogenesis through the Akt-TSC2-mTORC1 pathway / H. H. Zhang [et al.] // PLoS ONE. – 2009. – Vol. 4, N 7. – P. e6189. https://doi.org/10.1371/journal.pone.0006189Zhang H. H., Huang J., Duvel K., Boback B., Wu S., Squillace R. M., Wu C. L., Manning B. D. Insulin stimulates adipogenesis through the Akt-TSC2-mTORC1 pathway. PLoS ONE, 2009, vol. 4, no. 7, p. e6189. https://doi.org/10.1371/journal.pone.0006189Molecular mechanisms of PPAR-gamma governing MSC osteogenic and adipogenic differentiation / H. Zhuang [et al.] // Curr. Stem Cell Res. Ther. – 2015. – Vol. 11, N 3. – P. 255–264. https://doi.org/10.2174/1574888x10666150531173309Zhuang H., Zhang X., Zhu C., Tang X., Yu F., Shang G. W., Cai X. Molecular mechanisms of PPAR-gamma governing MSC osteogenic and adipogenic differentiation. Current Stem Cell Research and Therapy, 2015, vol. 11, no. 3, pp. 255–264. https://doi.org/10.2174/1574888x10666150531173309Regulation of adipocyte differentiation of bone marrow stromal cells by transcription factor GATA-2 / Y. Okitsu [et al.] // Biochem. Biophys. Res. Commun. – 2007. – Vol. 364, N 2. – P. 383–387. https://doi.org/10.1016/j.bbrc.2007.10.031Okitsu Y., Takahashi S., Minegishi N., Kameoka J., Kaku M., Yamamoto M., Sasaki T., Harigae H. Regulation of adipocyte differentiation of bone marrow stromal cells by transcription factor GATA-2. Biochemical and Biophysical Research Communications, 2007, vol. 364, no. 2, pp. 383–387. https://doi.org/10.1016/j.bbrc.2007.10.031TWIST family of basic helix-loop-helix transcription factors mediate human mesenchymal stem cell growth and commitment / S. Isenmann [et al.] // Stem Cells. – 2009. – Vol. 27, N 10. – P. 2457–2468. https://doi.org/10.1002/stem.181Isenmann S., Arthur A., Zannettino A. C., Turner J. L., Shi S., Glackin C. A., Gronthos S. TWIST family of basic helix-loop-helix transcription factors mediate human mesenchymal stem cell growth and commitment. Stem Cells, 2009, vol. 27, no. 10, pp. 2457–2468. https://doi.org/10.1002/stem.181MicroRNA-194 reciprocally stimulates osteogenesis and inhibits adipogenesis via regulating COUP-TFII expression / B. C. Jeong [et al.] // Cell Death Dis. – 2014. – Vol. 5, N 11. – P. e1532. https://doi.org/10.1038/cddis.2014.485Jeong B. C., Kang I. H., Hwang Y. C., Kim S. H., Koh J. T. MicroRNA-194 reciprocally stimulates osteogenesis and inhibits adipogenesis via regulating COUP-TFII expression. Cell Death and Disease, 2014, vol. 5, no. 11, p. e1532. https://doi.org/10.1038/cddis.2014.485Adult mesenchymal stem cells: differentiation potential and therapeutic applications / L. Jackson [et al.] // Postgrad. Med. – 2007. – Vol. 53, N 2. – P. 121–127. https://doi.org/10.4103/0022-3859.32215Jackson L., Jones D. R., Scotting P., Sottile V. Adult mesenchymal stem cells: differentiation potential and therapeutic applications. Journal of Postgraduate Medicine, 2007, vol. 53, no. 2, pp. 121–127. https://doi.org/10.4103/00223859.32215Charytonowicz, E. Alternate PAX3 and PAX7 C-terminal isoforms in myogenic differentiation and sarcomagenesis / E. Charytonowicz // Clin. Transl. Oncol. – 2011. – Vol. 13, N 3. – P. 194–203. https://doi.org/10.1007/s12094-011-0640-yCharytonowicz E., Matushansky I., Castillo-Martin M., Hricik T., Cordon-Cardo C., Ziman M. Alternate PAX3 and PAX7 C-terminal isoforms in myogenic differentiation and sarcomagenesis. Clinical and Translational Oncology, 2011, vol. 13, no. 3, pp. 194–203. https://doi.org.10.1007/s12094-011-0640-yPax3 activation promotes the differentiation of mesenchymal stem cells toward the myogenic lineage / E. J. Gang [et al.] // Exp. Cell Res. – 2008. – Vol. 314, N 8. – P. 1721–1733. https://doi.org/10.1016/j.yexcr.2008.02.016Gang E. J., Bosnakovski D., Simsek T., To K., Perlingeiro R. C. Pax3 activation promotes the differentiation of mesenchymal stem cells toward the myogenic lineage. Experimental Cell Research, 2008, vol. 314, no. 8, pp. 1721–1733. https://doi.org/10.1016/j.yexcr.2008.02.016MyoD transcription factor induces myogenesis by inhibiting Twist-1 through miR-206 / D. Koutalianos [et al.] // J. Cell Sci. – 2015. – Vol. 128, N 19. – P. 3631–3645. https://doi.org/10.1242/jcs.172288Koutalianos D., Koutsoulidou A., Mastroyiannopoulos N. P., Furling D., Phylactou L. A. MyoD transcription factor induces myogenesis by inhibiting Twist-1 through miR-206. Journal of Cell Science, 2015, vol. 128, no. 19, pp. 3631–3645. https://doi.org/10.1242/jcs.172288TAZ as a novel enhancer of MyoD-mediated myogenic differentiation / H. Jeong [et al.] // FASEB J. – 2010. – Vol. 24, N 9. – P. 3310–3320. https://doi.org/10.1096/fj.09-151324Jeong H., Bae S., An S. Y., Byun M. R., Hwang J. H., Yaffe M. B., Hong J. H., Hwang E. S. TAZ as a novel enhancer of MyoD-mediated myogenic differentiation. FASEB Journal, 2010, vol. 24, no. 9, pp. 3310–3320. https://doi.org/10.1096/fj.09-151324TNF alpha inhibits myogenic differentiation of C2C12 cells through NF-kappaB activation and impairment of IGF-1 signaling pathway/ Q. Zhao [et al.] // Biochem. Biophys. Res. Commun. – 2015. – Vol. 458, N 4. – P. 790–795. https://doi.org/10.1016/j.bbrc.2015.02.026Zhao Q., Yang S. T., Wang J. J., Zhou J., Xing S. S., Shen C. C. [et al.]. TNF alpha inhibits myogenic differentiation of C2C12 cells through NF-kappaB activation and impairment of IGF-1 signaling pathway. Biochemical and Biophysical Research Communications, 2015, vol. 458, no. 4, pp. 790–795. https://doi.org/10.1016/j.bbrc.2015.02.026Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation / K. E. Hatzistergos [et al.] // Circ. Res. – 2010. – Vol. 107, N 7. – P. 913–922. https://doi.org/10.1161/CIRCRESAHA.110.222703Hatzistergos K. E., Quevedo H., Oskouei B. N., Hu Q., Feigenbaum G. S., Margitich I. S. [et al.]. Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation. Circulation Research, 2010, vol. 107, no. 7, pp. 913–922. https://doi.org/10.1161/CIRCRESAHA.110.222703Thioredoxin-1 (Trx1) engineered mesenchymal stem cell therapy increased pro-angiogenic factors, reduced fibrosis and improved heart function in the infarcted rat myocardium / S. C. Suresh [et al.] // Int. J. Cardiol. – 2015. – Vol. 201. – P. 517–528. https://doi.org/10.1016/j.ijcard.2015.08.117Suresh S. C., Selvaraju V., Thirunavukkarasu M., Goldman J. W., Husain A., Palesty J. A., Sanchez J. A., McFadden D. W., Maulik N. Thioredoxin-1 (Trx1) engineered mesenchymal stem cell therapy increased pro-angiogenic factors, reduced fibrosis and improved heart function in the infarcted rat myocardium. International Journal of Cardiology, 2015, vol. 201, pp. 517–528. https://doi.org/10.1016/j.ijcard.2015.08.117Activation of Notch1 signalling promotes multi-lineage differentiation of c-Kit(POS)/NKX2.5(POS) bone marrow stem cells: implication in stem cell translational medicine / R. Ding [et al.] // Stem Cell Res. Ther. – 2015. – Vol. 6, N 1. – P. 91. https://doi.org/10.1186/s13287-015-0085-2Ding R., Jiang X., Ha Y., Wang Z., Guo J., Jiang H., Zheng S., Shen Z., Jie W. Activation of Notch1 signalling promotes multi-lineage differentiation of c-Kit(POS)/NKX2.5(POS) bone marrow stem cells: implication in stem cell translational medicine. Stem Cell Research & Therapy, 2015, vol. 6, no. 1, p. 91. https://doi.org/10.1186/s13287015-0085-2Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing / G. Chamberlain [et al.] // Stem Cells. – 2007. – Vol. 25, N 11. – P. 2739–2749. https://doi.org/10.1634/stemcells.2007-0197Chamberlain G., Fox J., Ashton B., Middleton J. Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells, 2007, vol. 25, no. 11, pp. 2739–2749. https://doi.org/10.1634/stemcells.2007-0197Sphingosine 1-phosphate induces differentiation of mesoangioblasts towards smooth muscle. A role for GATA6 / C. Donati [et al.] // PLoS ONE. – 2011. – Vol. 6, N 5. – P. e20389. https://doi.org/10.1371/journal.pone.0020389Donati C., Marseglia G., Magi A., Serrati S., Cencetti F., Bernacchioni C. [et al.]. Sphingosine 1-phosphate induces differentiation of mesoangioblasts towards smooth muscle. A role for GATA6. PLoS ONE, 2011, vol. 6, no. 5, p. e20389. https://doi.org/10.1371/journal.pone.0020389Peroxisome proliferator-activated receptor gamma negatively regulates the differentiation of bone marrow-derived mesenchymal stem cells toward myofibroblasts in liver fibrogenesis / S. Jia [et al.] // Cell Physiol. Biochem. – 2015. – Vol. 37, N 6. – P. 2085–2100. https://doi.org/10.1159/000438567Jia S., Liu X., Li W., Xie J., Yang L., Li L. Peroxisome proliferator-activated receptor gamma negatively regulates the differentiation of bone marrow-derived mesenchymal stem cells toward myofibroblasts in liver fibrogenesis. Cellular Physiology and Biochemistry, 2015, vol. 37, no. 6, pp. 2085–2100. https://doi.org/10.1159/000438567Mesenchymal stromal cells for sphincter regeneration: role of laminin isoforms upon myogenic differentiation / T. Seeger [et al.] // PLoS ONE. – 2015. – Vol. 10, N 9. – P. e0137419. https://doi.org/10.1371/journal.pone.0137419Seeger T., Hart M., Patarroyo M., Rolauffs B., Aicher W. K., Klein G. Mesenchymal stromal cells for sphincter regeneration: role of laminin isoforms upon myogenic differentiation. PLoS ONE, 2015, vol. 10, no. 9, p. e0137419. https://doi.org/10.1371/journal.pone.0137419Shi, N. From nerve to blood vessel: a new role of Olfm2 in smooth muscle differentiation from human embryonic stem cell-derived mesenchymal cells / N. Shi, S. Y. Chen // J. Biomed. Res. – 2015. – Vol. 29, N 4. – P. 261–263. https://doi.org/10.7555/JBR.29.20150027Shi N., Chen S. Y. From nerve to blood vessel: a new role of Olfm2 in smooth muscle differentiation from human embryonic stem cell-derived mesenchymal cells. Journal of BioMed Research, 2015, vol. 29, no. 4, pp. 261–263. https://doi.org/10.7555/JBR.29.20150027Pankajakshan, D. In vitro differentiation of bone marrow derived porcine mesenchymal stem cells to endothelial cells / D. Pankajakshan, V. Kansal, D. K. Agrawal // J. Tissue Eng. Regen. Med. – 2013. – Vol 7, N 11. – P. 911–920. https://doi.org/10.1002/term.1483Pankajakshan D., Kansal V., Agrawal D. K. In vitro differentiation of bone marrow derived porcine mesenchymal stem cells to endothelial cells. Journal of Tissue Engineering and Regenerative Medicine, 2013, vol. 7, no. 11, pp. 911–920. https://doi.org/10.1002/term.1483Ikhapoh, I. A. Synergistic effect of angiotensin II on vascular endothelial growth factor-A-mediated differentiation of bone marrow-derived mesenchymal stem cells into endothelial cells / I. A. Ikhapoh, C. J. Pelham, D. K. Agrawal // Stem Cell Res. Ther. – 2015. – Vol. 6, N 1. – P. 4. https://doi.org/10.1186/scrt538Ikhapoh I. A., Pelham C. J., Agrawal D. K. Synergistic effect of angiotensin II on vascular endothelial growth factorA-mediated differentiation of bone marrow-derived mesenchymal stem cells into endothelial cells. Stem Cell Research and Therapy, 2015, vol. 6, no. 1, p. 4. https://doi.org/10.1186/scrt538

The authors declare that there are no conflicts of interest present.