Human placenta‐derived adherent cells induce tolerogenic immune responses
Abstract
Human placenta‐derived adherent cells (PDAC cells) are a culture expanded, undifferentiated mesenchymal‐like population derived from full‐term placental tissue, with immunomodulatory and anti‐inflammatory properties. PDA‐001 (cenplacel‐L), an intravenous formulation of PDAC cells, is in clinical development for the treatment of autoimmune and inflammatory diseases. To elucidate the mechanisms underlying the immunoregulatory properties of PDAC cells, we investigated their effects on immune cell populations, including T cells and dendritic cells (DC) in vitro and in vivo. PDAC cells suppressed T‐cell proliferation in an OT‐II T‐cell adoptive transfer model, reduced the severity of myelin oligodendrocyte glycoprotein peptide‐induced experimental autoimmune encephalomyelitis and ameliorated inflammation in a delayed type hypersensitivity response model. In vitro, PDAC cells suppressed T‐cell proliferation and inhibited Th1 and Th17 differentiation. Analysis of tissues derived from PDAC cell‐treated animals revealed diminished CD86 expression on splenic DC, suggesting that they can also modulate DC populations. Furthermore, PDAC cells modulate the differentiation and maturation of mouse bone marrow‐derived DC. Similarly, human DC differentiated from CD14+ monocytes in the presence of PDAC cells acquired a tolerogenic phenotype. These tolerogenic DC failed to induce allogeneic T‐cell proliferation and differentiation toward Th1, but skewed T‐cell differentiation toward Th2. Inhibition of cyclo‐oxygenase‐2 activity resulted in a significant, but not complete, abrogation of PDAC cells’ effects on DC phenotype and function, implying a role for prostaglandin E2 in PDAC‐mediated immunomodulation. This study identifies modulation of DC differentiation toward immune tolerance as a key mechanism underlying the immunomodulatory activities of PDAC cells.
Number of times cited: 21
- Olena Pogozhykh, Volodymyr Prokopyuk, Constança Figueiredo and Denys Pogozhykh, Placenta and Placental Derivatives in Regenerative Therapies: Experimental Studies, History, and Prospects, Stem Cells International, 10.1155/2018/4837930, 2018, (1-14), (2018).
- Shuyang He, Joseph Gleason, Ewa Fik‐Rymarkiewicz, Andrea DiFiglia, Mini Bharathan, Andrew Morschauser, Ivana Djuretic, Yan Xu, Michael Krakovsky, Vladimir Jankovic, Charito Buensuceso, James Edinger, Uri Herzberg, Wolfgang Hofgartner and Robert Hariri, Human Placenta‐Derived Mesenchymal Stromal‐Like Cells Enhance Angiogenesis via T Cell‐Dependent Reprogramming of Macrophage Differentiation, STEM CELLS, 35, 6, (1603-1613), (2017).
- M.H. Abumaree, F.M. Abomaray, M.A. Alshabibi, A.S. AlAskar and B. Kalionis, Immunomodulatory properties of human placental mesenchymal stem/stromal cells, Placenta, 59, (87), (2017).
- Pamela Sarkar, Claire M. Rice and Neil J. Scolding, Cell Therapy for Multiple Sclerosis, CNS Drugs, 31, 6, (453), (2017).
- Alexandros Chatgilialoglu, Martina Rossi, Francesco Alviano, Paola Poggi, Chiara Zannini, Cosetta Marchionni, Francesca Ricci, Pier Luigi Tazzari, Valentina Taglioli, Philip C. Calder and Laura Bonsi, Restored in vivo-like membrane lipidomics positively influence in vitro features of cultured mesenchymal stromal/stem cells derived from human placenta, Stem Cell Research & Therapy, 10.1186/s13287-017-0487-4, 8, 1, (2017).
- Anna-Carin Lundell, Inger Nordström, Kerstin Andersson, Christina Lundqvist, Esbjörn Telemo, Silvia Nava, Helen Kaipe and Anna Rudin, IFN type I and II induce BAFF secretion from human decidual stromal cells, Scientific Reports, 7, (39904), (2017).
- Irina Yu. Kuzmina, Olga A. Kuzmina, Galyna I. Gubina-Vakulik and Iryna V. Dobrunova, State of Placentas in Pregnant Rats After Implantation of Cryopreserved Allogenic Placental Fragments, Problems of Cryobiology and Cryomedicine, 27, 2, (151), (2017).
- Shao-Yu Peng, Chien-wen Chou, Yu-Hsuan Kuo, Perng-Chih Shen and S.W. Steven Shaw, Potential differentiation of islet-like cells from pregnant cow-derived placental stem cells, Taiwanese Journal of Obstetrics and Gynecology, 56, 3, (306), (2017).
- Stephanie C Wu, Richard Pollak, Robert G Frykberg, Wei Zhou, Maha Karnoub, Vladimir Jankovic, Steven A Fischkoff and Denesh Chitkara, Safety and efficacy of intramuscular human placenta‐derived mesenchymal stromal‐like cells (cenplacel [PDA‐002]) in patients who have a diabetic foot ulcer with peripheral arterial disease, International Wound Journal, 14, 5, (823-829), (2017).
- Ilona Shapira, Nina Fainstein, Maria Tsirlin, Ilana Stav, Evgenia Volinsky, Claudia Moresi, Tamir Ben‐Hur and Raphael Gorodetsky, Placental Stromal Cell Therapy for Experimental Autoimmune Encephalomyelitis: The Role of Route of Cell Delivery, STEM CELLS Translational Medicine, 6, 4, (1286-1294), (2016).
- Aleksandar Francki, Kristen Labazzo, Shuyang He, Ellen Z. Baum, Stewart E. Abbot, Uri Herzberg, Wolfgang Hofgartner, Robert Hariri, Aleksandr Kaplunovsky, Jennifer Paredes, Allan Reduta, Eric Law, Ewa Fik, Sascha Abramson, Vivian R. Albert and Itschak Lamensdorf, Angiogenic properties of human placenta-derived adherent cells and efficacy in hindlimb ischemia, Journal of Vascular Surgery, 64, 3, (746), (2016).
- Assmaa O. Selim, Sally A. Selim, Sally M. Shalaby, Hala Mosaad and Taisir Saber, Neuroprotective effects of placenta-derived mesenchymal stromal cells in a rat model of experimental autoimmune encephalomyelitis, Cytotherapy, 10.1016/j.jcyt.2016.06.002, 18, 9, (1100-1113), (2016).
- Jianxia Hu, Gang Zhao, Lize Zhang, Cuixia Qiao, Aiping Di, Hong Gao and Hong Xu, Safety and therapeutic effect of mesenchymal stem cell infusion on moderate to severe ulcerative colitis, Experimental and Therapeutic Medicine, 12, 5, (2983), (2016).
- Beatriz Bravo, Marta I. Gallego, Ana I. Flores, Rafael Bornstein, Alba Puente-Bedia, Javier Hernández, Paz de la Torre, Elena García-Zaragoza, Raquel Perez-Tavarez, Jesús Grande, Alicia Ballester and Sara Ballester, Restrained Th17 response and myeloid cell infiltration into the central nervous system by human decidua-derived mesenchymal stem cells during experimental autoimmune encephalomyelitis, Stem Cell Research & Therapy, 7, 1, (2016).
- Gil Y. Melmed, William M. Pandak, Kevin Casey, Bincy Abraham, John Valentine, David Schwartz, Dahlia Awais, Issac Bassan, Simon Lichtiger, Bruce Sands, Stephen Hanauer, Robert Richards, Ioannis Oikonomou, Nimisha Parekh, Stephen Targan, Kristine Johnson, Robert Hariri and Steven Fischkoff, Human Placenta-derived Cells (PDA-001) for the Treatment of Moderate-to-severe Crohnʼs Disease, Inflammatory Bowel Diseases, 21, 8, (1809), (2015).
- Hong-Jung Chen, Chien-Hsi Chen, Ming-Yao Chang, Da-Ching Tsai, Ellen Z. Baum, Robert Hariri, Uri Herzberg and Patrick C.H. Hsieh, Human Placenta‐Derived Adherent Cells Improve Cardiac Performance in Mice With Chronic Heart Failure, STEM CELLS Translational Medicine, 4, 3, (269-275), (2015).
- Gi Jin Kim, Advanced Research on Stem Cell Therapy for Hepatic Diseases: Potential Implications of a Placenta-derived Mesenchymal Stem Cell-based Strategy, Hanyang Medical Reviews, 10.7599/hmr.2015.35.4.207, 35, 4, (207), (2015).
- Robert J. Hariri and Steven Fischkoff, Translational Regenerative Medicine, (39), (2015).
- Paola Vacca, Elisa Montaldo, Chiara Vitale, Daniele Croxatto, Lorenzo Moretta and Maria Cristina Mingari, MSC and innate immune cell interactions: A lesson from human decidua, Immunology Letters, 168, 2, (170), (2015).
- Fred D. Lublin, James D. Bowen, John Huddlestone, Marcelo Kremenchutzky, Adam Carpenter, John R. Corboy, Mark S. Freedman, Lauren Krupp, Corri Paulo, Robert J. Hariri and Steven A. Fischkoff, Human placenta-derived cells (PDA-001) for the treatment of adults with multiple sclerosis: A randomized, placebo-controlled, multiple-dose study, Multiple Sclerosis and Related Disorders, 3, 6, (696), (2014).
- Antonietta R. Silini, Anna Cargnoni, Marta Magatti, Stefano Pianta and Ornella Parolini, The Long Path of Human Placenta, and Its Derivatives, in Regenerative Medicine, Frontiers in Bioengineering and Biotechnology, 10.3389/fbioe.2015.00162, 3, (2015).
