Three-Dimensional Culture of Umbilical Cord Mesenchymal Stem Cells Effectively Promotes Platelet Recovery in Immune Thrombocytopenia

• Published in: Biological & pharmaceutical bulletin Vol. 43; no. 7; pp. 1052 - 1060
• Main Authors: Gong, Xiangcui, Sun, Di, Li, Zhenghao, Shi, Qing, Li, Dong, Ju, Xiuli
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.07.2020; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Animals; Apoptosis; Autoimmune diseases; Blood Platelets - physiology; Body weight; Bone marrow; Cell activation; Cell culture; Cell Culture Techniques - methods; Cytokines; Extracellular matrix; Female; Gene expression; Guinea Pigs; Histocompatibility antigen HLA; Human Umbilical Vein Endothelial Cells - physiology; Humans; Idiopathic thrombocytopenic purpura; immune thrombocytopenia; Immunogenicity; immunoregulation; Intravenous administration; Lymphocytes; Male; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal stem cells; Mesenchymal Stem Cells - physiology; Mice; Mice, Inbred BALB C; Platelets; Polyvinyls - administration & dosage; Pregnancy; Purpura, Thrombocytopenic, Idiopathic - immunology; Purpura, Thrombocytopenic, Idiopathic - therapy; Serum levels; Spleen; Stem cell transplantation; Stem cells; three-dimensional culture; Thrombocytopenia; Umbilical cord; umbilical cord mesenchymal stem cell; γ-Interferon; three-dimensional culture; immunoregulation; immune thrombocytopenia; umbilical cord mesenchymal stem cell
• ISSN: 0918-6158; 1347-5215; 1347-5215
• DOI: 10.1248/bpb.b19-01069

Mesenchymal stem cells (MSCs) can effectively regulate immune cell functions and therefore are promising for the treatment of autoimmune disorders, such as immune thrombocytopenia (ITP). Recent research has shown that three-dimensional (3D) culture method have many advantages over conventional culture with respect to MSC secretion and immunogenicity. In this study, 2D and 3D cultured MSCs were used to evaluate cytokine secretion, extracellular matrix (ECM) gene expression, immune regulatory activity, and therapeutic effects in a mouse model of ITP. MSCs cultured on scaffolds had higher expression levels of immune regulatory genes, such as IDO1, HLA-G, and PTGS2, and greater inhibitory activity against lymphocyte activation that those of 2D-MSCs. In addition, 3D-MSCs exhibited higher ECM expression and greater protection against interferon-γ (IFN-γ)-induced apoptosis. In a mouse study, ITP was induced by guinea pig anti-mouse platelet serum injections. Based on enzyme-linked immunosorbent assays, serum levels of the suppressive cytokine interleukin (IL)-10 were higher and IFN-γ levels were lower after intravenous injection with 3D-MSCs and with 2D-MSCs. Additionally, 3D-MSCs improved the body weight, spleen index, and platelet index relative to those for 2D-MSCs. Bone marrow homing was also significantly enhanced in the 3D group. Therefore, the 3D culture of MSCs is an effective technique for the treatment of ITP.