Genes & CellsGenes & CellsГены и КлеткиGenes and Cells2313-18292500-2562Human Stem Cells Institute12047410.23868/gc120474ArticlesСтатьиReview ArticleUmbilical cord-derived multipotent mesenchymal stromal cells: biological properties and clinical applicationsМультипотентные мезенхимальные стромальные клетки пупочного канатика: биологические свойства и клиническое применениеArutyunyanI. VАрутюнянИ. ВMakarovA. VМакаровА. ВElchaninovA. VЕльчаниновА. ВFatkhudinovT. KhФатхудиновТ. Хfatkhudinov@gmail.comV.I. Kulakov Research Center for Obstetrics, Gynecology and Perinatology of Ministry of Healthcare of the Russian FederationНаучный центр акушерства, гинекологии и перинатологии им. академика В.И. КулаковаScientific Research Institute of Human MorphologyНаучно-исследовательский институт морфологии человекаN.I. Pirogov Russian National Research Medical University, Ministry of Healthcare of the Russian FederationРоссийский национальный исследовательский медицинский университет им. Н.И. Пирогова15062015102VOL 10, NO2 (2015)ТОМ 10, №2 (2015)303805012023Copyright ©; 2015, Eco-VectorCopyright ©; 2015, Эко-Вектор2015Eco-VectorЭко-Векторhttps://genescells.ru/2313-1829/article/view/120474

The article presents the current literature evidence and own data on the origin and properties of human umbilical cord-derived multipotent mesenchymal stromal cells including proliferative potential, plasticity, stability of caryotype and phenotype, and immunomodulatory activity A review of clinical trials using this cell type is performed Prospects for the use of multipotent stromal cells, derived from umbilical cord, in cell transplantation associate with the need for specialized biobanking and transplant standardization criteria

Представлены современные литературные и собственные данные о происхождении и свойствах мультипотентных мезенхимальных стромальных клеток, выделенных из пупочного канатика человека: пролиферативном потенциале, пластичности, стабильности кариотипа и фенотипа, иммуномодулирующей активности. Приведен обзор клинических исследований с использованием данного типа клеток Перспективы использования мультипотентных мезенхимальных стромальных клеток пупочного канатика в клеточной трансплантологии обуславливают необходимость создания специализированных биобанков и стандартизации самого трансплантата

human umbilical cordmultipotent mesenchymal stromal cellsclinical trialsпупочный канатик человекамультипотентные мезенхимальные стромальные клеткиклинические исследованияBongso A., Fong C-Y. Phenotype and Differentiation Potential of Stromal Populations Obtained from Various Zones of Human Umbilical Cord: An Overview. Stem Cell Reviews and Reports 2013; 9(2): 226-40Щеголев А.И., Дубова Е.А., Павлов К.А. Морфология плаценты. Москва: НЦАГиП им. В. И. Кулакова; 2010.Knudtzon S. In vitro growth of granulocytic colonies from circulating cells in human cord blood. Blood 1974; 43(3): 357-61.McElreavey K.D., Irvine A.I., Ennis K.T. et al. Isolation, culture and characterisation of fibroblast-like cells derived from the Wharton's jelly portion of human umbilical cord. Biochem. Soc. Trans. 1991; 19(1): 29S.Wang H.S., Hung S.C., Peng S.T. et al. Mesenchymal stem cells in the Wharton's jelly of the human umbilical cord. Stem Cells 2004; 22(7): 1330-7.Dominici M., Le Blanc K., Mueller I. et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8(4): 315-7.Wang X.Y., Lan Y., He W.Y. et al. Identification of mesenchymal stem cells in aorta-gonad-mesonephros and yolk sac of human embryos. Blood 2008; 111(4): 2436-43.Li D.R., Cai J.H. Methods of isolation, expansion, differentiating induction and preservation of human umbilical cord mesenchymal stem cells. Chin. Med. J. (Engl. ) 2012; 125(24): 4504-10.Trivanovic D., Kocic J., Mojsilovic S. et al. Mesenchymal stem cells isolated from peripheral blood and umbilical cord Wharton's jelly. Srp. Arh. Celok Lek. 2013; 141(3-4): 178-86.Salehinejad P., Alitheen N.B., Ali A.M. et al. Comparison of different methods for the isolation of mesenchymal stem cells from human umbilical cord Wharton's jelly. In Vitro Cell Dev. Biol. Anim. 2012; 48(2): 75-83.Margossian T., Reppel L., Makdissy N. et al. Mesenchymal stem cells derived from Wharton's jelly: comparative phenotype analysis between tissue and in vitro expansion. Biomed. Mater. Eng. 2012; 22(4): 243-54.Bieback K., Brinkmann I. Mesenchymal stromal cells from human perinatal tissues: From biology to cell therapy. World J. Stem Cells 2010; 2(4): 81-92.Chatzistamatiou T.K., Papassavas A.C., Michalopoulos E. et al. Optimizing isolation culture and freezing methods to preserve Wharton's jelly's mesenchymal stem cell (MSC) properties: an MSC banking protocol validation for the Hellenic. Cord Blood Bank Transfusion 2014; 54(12): 3108-20.Can A., Karahuseyinoglu S. Concise review: human umbilical cord stroma with regard to the source of fetus-derived stem cells. Stem Cells 2007; 25(11): 2886-95.Batsali A.K., Kastrinaki M.C., Papadaki H.A. et al. Mesenchymal stem cells derived from Wharton's Jelly of the umbilical cord: biological properties and emerging clinical applications. Curr. Stem Cell Res. Ther. 2013; 8(2): 144-55.Kadam S.S., Tiwari S., Bhonde R.R. Simultaneous isolation of vascular endothelial cells and mesenchymal stem cells from the human umbilical cord. In Vitro Cell Dev. Biol. Anim. 2009; 45(1-2): 23-7.Bakhshi T., Zabriskie R.C., Bodie S. et al. Mesenchymal stem cells from the Wharton's jelly of umbilical cord segments provide stromal support for the maintenance of cord blood hematopoietic stem cells during long-term ex vivo culture. Transfusion 2008; 48(12): 2638-44.Majumdar D., Bhonde R., Datta I. Influence of ischemic microenvironment on human Wharton's Jelly mesenchymal stromal cells. Placenta 2013; 34(8): 642-9.Tantrawatpan C., Manochantr S., Kheolamai P. et al. Pluripotent gene expression in mesenchymal stem cells from human umbilical cord Wharton's jelly and their differentiation potential to neural-like cells. J. Med. Assoc. Thai. 2013; 96(9): 1208-17.Fong C.Y., Richards M., Manasi N. et al. Comparative growth behaviour and characterization of stem cells from human Wharton's jelly. Reprod. Biomed. Online 2007; 15(6): 708-18.Drela K., Sarnowska A., Siedlecka P. et al. Low oxygen atmosphere facilitates proliferation and maintains undifferentiated state of umbilical cord mesenchymal stem cells in an hypoxia inducible factor-dependent manner. Cytotherapy 2014; 16(7): 881-92.Amiri F., Halabian R., Dehgan Harati M et al. Positive selection of Wharton's jelly-derived CD105+ cells by MACS technique and their subsequent cultivation under suspension culture condition: a simple, versatile culturing method to enhance the multipotentiality of mesenchymal stem cells. Hematology 2014; 20(4): 208-16.He H., Nagamura-Inoue T., Tsunoda H. et al. Stage-specific embryonic antigen 4 in Wharton's jelly-derived mesenchymal stem cells is not a marker for proliferation and multipotency Tissue Eng Part A 2014; 20(7-8): 1314-24.Lu L.L., Liu Y.J., Yang S.G. et al. Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials. Haematologica 2006; 91(8): 1017-26.Shaer A., Azarpira N., Aghdaie M.H. et al. Isolation and characterization of Human Mesenchymal Stromal Cells Derived from Placental Decidua Basalis; Umbilical cord Wharton's Jelly and Amniotic Membrane. Pak. J. Med. Sci. 2014; 30(5): 1022-6.Li X., Bai J., Ji X. et al. Comprehensive characterization of four different populations of human mesenchymal stem cells as regards their immune properties, proliferation and differentiation Int. J. Mol. Med. 2014; 34(3): 695-704.Karahuseyinoglu S., Cinar O., Kilic E. et al. Biology of stem cells in human umbilical cord stroma: in situ and in vitro surveys Stem Cells 2007; 25(2): 319-31.Ruan Z.B., Zhu L., Yin Y.G. et al. Karyotype stability of human umbilical cord-derived mesenchymal stem cells during in vitro culture. Exp. Ther. Med. 2014; 8(5): 1508-12.Chen G., Yue A., Ruan Z. et al. Human umbilical cord-derived mesenchymal stem cells do not undergo malignant transformation during long-term culturing in serum-free medium PLoS One 2014; 9(6): e98565Sabapathy V., Sundaram B., VM S. et al. Human Wharton's Jelly Mesenchymal Stem Cells plasticity augments scar-free skin wound healing with hair growth. PLoS One 2014; 9(4): e93726.Taghizadeh R.R., Cetrulo K.J., Cetrulo C.L. Wharton's Jelly stem cells: future clinical applications. Placenta 2011; 32 Suppl 4: S311-5.Gauthaman K., Fong C.Y., Suganya C.A. et al. Extra-embryonic human Wharton's jelly stem cells do not induce tumorigenesis, unlike human embryonic stem cells. Reprod. Biomed. Online 2012; 24(2): 235-46Liang X.J., Chen X.J., Yang D.H. et al. Differentiation of human umbilical cord mesenchymal stem cells into hepatocyte-like cells by hTERT gene transfection in vitro. Cell Biol. Int. 2012; 36(2): 215-21Subramanian A., Shu-Uin G., Kae-Siang N. et al. Human umbilical cord Wharton's jelly mesenchymal stem cells do not transform to tumor-associated fibroblasts in the presence of breast and ovarian cancer cells unlike bone marrow mesenchymal stem cells. J. Cell Biochem. 2012; 113(6): 1886-95.Han Y., Chai J., Sun T. et al. Differentiation of human umbilical cord mesenchymal stem cells into dermal fibroblasts in vitro Biochem Biophys. Res. Commun. 2011; 413(4): 561-5.Kadam S.S., Bhonde R.R. Islet neogenesis from the constitutively nestin expressing human umbilical cord matrix derived mesenchymal stem cells. Islets 2010; 2(2): 112-20.Wang H., Zhao T., Xu F. et al. How important is differentiation in the therapeutic effect of mesenchymal stromal cells in liver disease? Cytotherapy 2014; 16(3): 309-18.Datta I., Mishra S., Mohanty L. et al. Neuronal plasticity of human Wharton's jelly mesenchymal stromal cells to the dopaminergic cell type compared with human bone marrow mesenchymal stromal cells. Cytotherapy 2011; 13(8): 918-32.Yang S., Ma K., Feng C. et al. Capacity of human umbilical cord-derived mesenchymal stem cells to differentiate into sweat gland-like cells: a preclinical study. Front. Med. 2013; 7(3):345-53.Li N., Pan S., Zhu H. et al. BMP4 promotes SSEA-1( + ) hUC-MSC differentiation into male germ-like cells in vitro Cell Prolif 2014; 47(4): 299-309.Latifpour M., Shakiba Y., Amidi F. et al. Differentiation of Human Umbilical Cord Matrix-Derived Mesenchymal Stem Cells into Germ-Like Cells. Avicenna J. Med. Biotechnol. 2014; 6(4): 218-27.Chen M.Y., Lie P. C., Li Z.L. et al. Endothelial differentiation of Wharton's jelly-derived mesenchymal stem cells in comparison with bone marrow-derived mesenchymal stem cells Exp Hematol 2009; 37(5): 629-40.Wu L.F., Wang N.N., Liu Y.S. et al. Differentiation of Wharton's jelly primitive stromal cells into insulin-producing cells in comparison with bone marrow mesenchymal stem cells Tissue Eng Part A 2009; 15(10): 2865-73.Balasubramanian S., Thej C., Venugopal P. et al. Higher propensity of Wharton's jelly derived mesenchymal stromal cells towards neuronal lineage in comparison to those derived from adipose and bone marrow. Cell Biol. int. 2013; 37(5): 507-15.Li J.F., Yin H.L., Shuboy A. et al. Differentiation of hUC-MSC into dopaminergic-like cells after transduction with hepatocyte growth factor. Mol. Cell Biochem. 2013; 381(1-2): 183-90.Liu A.M., Lu G., Tsang K.S. et al. Umbilical cord-derived mesenchymal stem cells with forced expression of hepatocyte growth factor enhance remyelination and functional recovery in a rat intracerebral hemorrhage model. Neurosurgery 2010; 67(2): 357-65.Wei X., Peng G., Zheng S. et a.l Differentiation of umbilical cord mesenchymal stem cells into steroidogenic cells in comparison to bone marrow mesenchymal stem cells. Cell Prolif. 2012; 45(2): 101-10.Joerger-Messerli M., Brühlmann E., Bessire A. et al. Preeclampsia enhances neuroglial marker expression in umbilical cord Wharton's jelly-derived mesenchymal stem cells. J. Matern. Fetal Neonatal. Med. 2014; 5: 1-6.Messerli M., Wagner A., Sager R. et al. Stem cells from umbilical cord Wharton's jelly from preterm birth have neuroglial differentiation potential. Reprod. Sci. 2013; 20(12): 1455-64.Penolazzi L., Vecchiatini R., Bignardi S. et al. influence of obstetric factors on osteogenic potential of umbilical cord-derived mesenchymal stem cells. Reprod. Biol. Endocrinol. 2009; 7: 106.Kim J., Piao Y., Pak Y.K. et al. Umbilical cord mesenchymal stromal cells affected by gestational diabetes mellitus display premature aging and mitochondrial dysfunction. Stem Cells Dev. 2015; 24(5): 575-86.Weiss M.L., Anderson C., Medicetty S. et al. immune properties of human umbilical cord Wharton's jelly-derived cells Stem Cells 2008; 26(11): 2865-74.Deng Y., Yi S., Wang G. et al. Umbilical cord-derived mesenchymal stem cells instruct dendritic cells to acquire tolerogenic phenotypes through the iL-6-mediated upregulation of SOCS1. Stem Cells Dev. 2014; 23(17): 2080-92.Chatterjee D., Marquardt N., Tufa D. et al. Role of gamma-secretase in human umbilical-cord derived mesenchymal stem cell mediated suppression of NK cell cytotoxicity Cell Commun Signal 2014; 12(1): 63.Liu R., Su D., Zhou M. et al. Umbilical cord mesenchymal stem cells inhibit the differentiation of circulating T follicular helper cells in patients with primary Sjögren's syndrome through the secretion of indoleamine 2,3-dioxygenase. Rheumatology (Oxford) 2015; 54(2): 332-42Prockop D.J. Concise review: two negative feedback loops place mesenchymal stem/stromal cells at the center of early regulators of inflammation. Stem Cells 2013; 31(10): 2042-6.Hartmann I., Hollweck T., Haffner S. et al. Umbilical cord tissue-derived mesenchymal stem cells grow best under GMP-compliant culture conditions and maintain their phenotypic and functional properties. J. immunol. Methods 2010; 363(1): 80-9.National Library of Medicine. URL: http://www. ncbi.nlm.nih. gov/pubmed/ (дата обращения 14.04. 2015).Liu L., Mao Q., Chu S. et al. intranasal versus intraperitoneal delivery of human umbilical cord tissue-derived cultured mesenchymal stromal cells in a murine model of neonatal lung injury Am J Pathol 2014; 184(12): 3344-58.Donders R., Vanheusden M., Bogie J.F. et al. Human Wharton's jelly-derived stem cells display immunomodulatory properties and transiently improve rat experimental autoimmune encephalomyelitis Cell Transplant. 2015; 24(10):2077-98.Lin Y., Lin L., Wang Q. et al. Transplantation of human umbilical mesenchymal stem cells attenuates dextran sulfate sodium-induced colitis in mice. Clin. Exp. Pharmacol. Physiol. 2015; 42(1): 76-86.Santos Nascimento D., Mosqueira D., Sousa L.M. et al. Human umbilical cord tissue-derived mesenchymal stromal cells attenuate remodeling after myocardial infarction by proangiogenic, antiapoptotic, and endogenous cell-activation mechanisms Stem Cell Res. Ther. 2014; 5(1): 5.Santos J. M., Barcia R.N., Simöes S.I. et al. The role of human umbilical cord tissue-derived mesenchymal stromal cells (UCX®) in the treatment of inflammatory arthritis. J. Transl. Med. 2013; 11: 18.Liu A.M., Lu G., Tsang K.S. et al. Umbilical cord-derived mesenchymal stem cells with forced expression of hepatocyte growth factor enhance remyelination and functional recovery in a rat intracerebral hemorrhage model. Neurosurgery 2010; 67(2): 357-65Li J., Zheng C.Q., Li Y. et al. Hepatocyte growth factor gene-modified mesenchymal stem cells augment sinonasal wound healing Stem Cells Dev. 2015; 24(15):1817-30.Tang J., Wang J., Guo L. et al. Mesenchymal stem cells modified with stromal cell-derived factor 1 alpha improve cardiac remodeling via paracrine activation of hepatocyte growth factor in a rat model of myocardial infarction. Mol. Cells 2010; 29(1): 9-19.Database of publicly and privately supported clinical studies of human participants. URL: http://www. clinicaltrials. gov/ (дата обращения 03. 03. 2015).Hu J., Yu X., Wang Z. et al. Long term effects of the implantation of Wharton's jelly-derived mesenchymal stem cells from the umbilical cord for newly-onset type 1 diabetes mellitus Endocr J 2013; 60(3): 347-57.Wang D. , Feng X. , Lu L. et al. A CD8 T cell/indoleamine 2,3-dioxygenase axis is required for mesenchymal stem cell suppression of human systemic lupus erythematosus Arthritis Rheumatol 2014; 66(8): 2234-45.Sun L., Wang D., Liang J. et al. Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus. Arthritis Rheum. 2010; 62(8): 2467-75.Chang Y.S., Ahn S.Y., Yoo H.S. et al. Mesenchymal stem cells for bronchopulmonary dysplasia: dose-escalation clinical trial J Pediatr. 2014; 164(5): 966-72. e6.Zhang Z., Fu J., Xu X. et al. Safety and immunological responses to human mesenchymal stem cell therapy in difficult-to-treat HiV-1-infected patients. AiDS 2013; 27(8): 1283-93.Wang L., Li J., Liu H. et al. Pilot study of umbilical cord-derived mesenchymal stem cell transfusion in patients with primary biliary cirrhosis. J. Gastroenterol. Hepatol. 2013; 28 Suppl 1: 85-92.Shi M., Zhang Z., Xu R. et al. Human mesenchymal stem cell transfusion is safe and improves liver function in acute-on-chronic liver failure patients. Stem Cells Transl. Med. 2012; 1(10): 725-31Liang L., Han Z.C. Umbilical Cord Mesenchymal Stem Cells: Biology and Clinical Application. in: Stoltz J.F., editor. Regenerative Medicine and Cell Therapy. Amsterdam: iOS Press; 2012. p. 62-70.Martins J.P., Santos J.M., de Almeida J.M. et al. Towards an advanced therapy medicinal product based on mesenchymal stromal cells isolated from the umbilical cord tissue: quality and safety data Stem Cell. Res. Ther. 2014; 5(1): 9.Cooper K., Viswanathan C. Establishment of a mesenchymal stem cell bank. Stem Cells int. 2011; 2011: 905621.Уфимцева А.И., Канов Е.В. Характеристика и ex vivo экспансия гемопоэтических стволовых и прогениторных клеток пуповинной крови. КТТИ 2012; Vii(4) 21-7.Secco M., Zucconi E., Vieira N.M. et al. Mesenchymal stem cells from umbilical cord: do- not discard the cord! Neuromuscul. Disord. 2008; 18(1): 17-8.