三种人胎盘组织来源间充质干细胞的生物学特性
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摘要
背景:胎盘组织结构复杂,包括胎儿侧的羊膜、绒毛膜以及母体侧的蜕膜等。尽管一些文献已经报道这3种组织来源间充质干细胞具有一些共有的生物学特性,但是对于来自同一胎盘不同组织来源间充质干细胞是否存在不同的生物学特性,目前仍缺乏定量的研究分析。目的:探讨人胎盘不同组织来源间充质干细胞的生物学特性,包括分化潜能和免疫调节功能。方法:利用酶消化法从1例男婴胎盘组织分离羊膜来源间充质干细胞、绒毛膜来源间充质干细胞和蜕膜来源间充质干细胞。系统性研究这3种间充质干细胞的生物学特性,包括细胞形态、表面标志物表达、核型分析、成脂、成骨分化能力以及调节性T细胞的增殖能力。结果与结论:(1)3种细胞均呈成纤维细胞形态,均表达间充质干细胞的表面标志物:高表达CD73、CD90和CD105,低表达CD14、CD19、CD34、CD45和HLA-DR;(2)羊膜、绒毛膜间充质干细胞核型与胎儿相同,蜕膜间充质干细胞核型与母体相同;(3)3种间充质干细胞成脂分化能力存在显著性差异,依次为蜕膜间充质干细胞>绒毛膜间充质干细胞>羊膜间充质干细胞(P <0.05);相反,羊膜间充质干细胞的成骨分化能力明显高于蜕膜间充质干细胞(P <0.05);(4)羊膜间充质干细胞和绒毛膜间充质干细胞促进调节性T细胞增殖的能力显著高于蜕膜间充质干细胞;(5)结果表明,人胎盘羊膜、绒毛膜、蜕膜组织来源间充质干细胞具有不同的核型、成脂、成骨分化潜能和免疫调节能力,为不同种子细胞治疗相关疾病达到最佳效果提供了一定的参考。
BACKGROUND: The placental tissue structure is complex, including the amniotic membrane, chorion, and decidua from the mother. Mesenchymal stem cells derived from different tissues of the same placenta have been reported to have similar biological characteristics. To date, there is no study regarding quantitative comparison of differentiation potential and immunomodulatory function of mesenchymal stem cells derived from different tissues of human placenta. OBJECTIVE: To investigate the biological characteristics including differentiation potential and immunomodulatory function of mesenchymal stem cells derived from different tissues of human placenta. METHODS: The amnion-, chorion-, and decidua-derived mesenchymal stem cells were isolated from the placental tissue of a baby boy by enzymatic digestion method. The biological characteristics of these three kinds of mesenchymal stem cells were systematically investigated including cell morphology, immunophenotypes, karyotypeanalysis, adipogenic and osteogenic differentiation potential, and Treg cells proliferation capacity. RESULTS AND CONCLUSION: All three kinds of mesenchymal stem cells showed fibroblast-like morphology and expressed the surface markers of mesenchymal stem cells with high expressions of CD73, CD90 and CD105, as well as low expressions of CD14, CD19, CD34, CD45 and HLA-DR. The karyotypes of the amnion-and chorion-derived mesenchymal stem cells were the same as the fetus, and decidua-derived mesenchymal stem cells had the same karyotype as the mother. There were significant differences in adipogenic differentiation capacity between three kinds of mesenchymal stem cells(amnion-derived mesenchymal stem cells > chorion-derived mesenchymal stem cells > decidua-derived mesenchymal stem cells; P < 0.05). In contrast, the osteogenic differentiation capacity of amnion-derived mesenchymal stem cells was remarkably higher than that of decidua-derived mesenchymal stem cells(P < 0.05). The amnion-and chorion-derived mesenchymal stem cells had the higher potential of Treg cell proliferation induction than decidua-derived mesenchymal stem cells. These findings indicate that three sources of human placenta-derived mesenchymal stem cells have different karyotypes, adipogenic and osteogenic differentiation potential, and immunomodulatory capability, providing a variety of ideal seed cell sources for disease treatment.
BACKGROUND: The placental tissue structure is complex, including the amniotic membrane, chorion, and decidua from the mother. Mesenchymal stem cells derived from different tissues of the same placenta have been reported to have similar biological characteristics. To date, there is no study regarding quantitative comparison of differentiation potential and immunomodulatory function of mesenchymal stem cells derived from different tissues of human placenta. OBJECTIVE: To investigate the biological characteristics including differentiation potential and immunomodulatory function of mesenchymal stem cells derived from different tissues of human placenta. METHODS: The amnion-, chorion-, and decidua-derived mesenchymal stem cells were isolated from the placental tissue of a baby boy by enzymatic digestion method. The biological characteristics of these three kinds of mesenchymal stem cells were systematically investigated including cell morphology, immunophenotypes, karyotypeanalysis, adipogenic and osteogenic differentiation potential, and Treg cells proliferation capacity. RESULTS AND CONCLUSION: All three kinds of mesenchymal stem cells showed fibroblast-like morphology and expressed the surface markers of mesenchymal stem cells with high expressions of CD73, CD90 and CD105, as well as low expressions of CD14, CD19, CD34, CD45 and HLA-DR. The karyotypes of the amnion-and chorion-derived mesenchymal stem cells were the same as the fetus, and decidua-derived mesenchymal stem cells had the same karyotype as the mother. There were significant differences in adipogenic differentiation capacity between three kinds of mesenchymal stem cells(amnion-derived mesenchymal stem cells > chorion-derived mesenchymal stem cells > decidua-derived mesenchymal stem cells; P < 0.05). In contrast, the osteogenic differentiation capacity of amnion-derived mesenchymal stem cells was remarkably higher than that of decidua-derived mesenchymal stem cells(P < 0.05). The amnion-and chorion-derived mesenchymal stem cells had the higher potential of Treg cell proliferation induction than decidua-derived mesenchymal stem cells. These findings indicate that three sources of human placenta-derived mesenchymal stem cells have different karyotypes, adipogenic and osteogenic differentiation potential, and immunomodulatory capability, providing a variety of ideal seed cell sources for disease treatment.
引文
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[2]Sardesai VS,Shafiee A,Fisk NM,et al.Avoidance of Maternal Cell Contamination and Overgrowth in Isolating Fetal Chorionic Villi Mesenchymal Stem Cells from Human Term Placenta.Stem Cells Transl Med.2017;6(4):1070-1084.
[3]Consentius C,Reinke P,Volk HD.Immunogenicity of allogeneic mesenchymal stromal cells:what has been seen in vitro and in vivo.Regen Med.2015;10(3):305-315.
[4]Bellavia M,Altomare R,Cacciabaudo F,et al.Towards an ideal source of mesenchymal stem cell isolation for possible therapeutic application in regenerative medicine.Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub.2014;158(3):356-360.
[5]Li M,Zhao Y,Hao H,et al.Mesenchymal stem cell-based therapy for nonhealing wounds:today and tomorrow.Wound Repair Regen.2015;23(4):465-482.
[6]Kim R,Park SI,Lee CY,et al.Alternative new mesenchymal stem cell source exerts tumor tropism through ALCAM and N-cadherin via regulation of microRNA-192 and-218.Mol Cell Biochem.2017;427(1-2):177-185.
[7]Ruan H,Xiao R,Jiang X,et al.Biofunctionalized self-assembly of peptide amphiphile induces the differentiation of bone marrow mesenchymal stem cells into neural cells.Mol Cell Biochem.2018 Jun 21.doi:10.1007/s11010-018-3386-9.[Epub ahead of print]
[8]Dezawa M.Muse Cells Provide the Pluripotency of Mesenchymal Stem Cells:Direct Contribution of Muse Cells to Tissue Regeneration.Cell Transplant.2016;25(5):849-861.
[9]Faghihi F,Mirzaei E,Ai J,et al.Erratum to:Differentiation Potential of Human Chorion-Derived Mesenchymal Stem Cells into Motor Neuron-Like Cells in Two-and Three-Dimensional Culture Systems.Mol Neurobiol.2016;53(3):1873.
[10]Wang X,Lazorchak AS,Song L,et al.Immune modulatory mesenchymal stem cells derived from human embryonic stem cells through a trophoblast-like stage.Stem Cells.2016;34(2):380-391.
[11]Valencia J,Blanco B,Yá?ez R,et al.Comparative analysis of the immunomodulatory capacities of human bone marrow-and adipose tissue-derived mesenchymal stromal cells from the same donor.Cytotherapy.2016;18(10):1297-1311.
[12]Lim JY,Im KI,Lee ES,et al.Enhanced immunoregulation of mesenchymal stem cells by IL-10-producing type 1 regulatory T cells in collagen-induced arthritis.Sci Rep.2016;6:26851.
[13]Ma OK,Chan KH.Immunomodulation by mesenchymal stem cells:Interplay between mesenchymal stem cells and regulatory lymphocytes.World J Stem Cells.2016;8(9):268-278.
[14]Wu M,Zhang R,Zou Q,et al.Comparison of the Biological Characteristics of Mesenchymal Stem Cells Derived from the Human Placenta and Umbilical Cord.Sci Rep.2018;8(1):5014.
[15]Timmins NE,Kiel M,Günther M,et al.Closed system isolation and scalable expansion of human placental mesenchymal stem cells.Biotechnol Bioeng.2012;109(7):1817-1826.
[16]Du L,Lv R,Yang X,et al.Hypoxic conditioned medium of placenta-derived mesenchymal stem cells protects against scar formation.Life Sci.2016;149:51-57.
[17]Araújo AB,Salton GD,Furlan JM,et al.Comparison of human mesenchymal stromal cells from four neonatal tissues:Amniotic membrane,chorionic membrane,placental decidua and umbilical cord.Cytotherapy.2017;19(5):577-585.
[18]Eidem HR,Ackerman WE 4th,McGary KL,et al.Gestational tissue transcriptomics in term and preterm human pregnancies:a systematic review and meta-analysis.BMC Med Genomics.2015;8:27.
[19]Gan WT,Sun X,Lu Y.Comparison of Biological Characteristics between Human Amnion Epithelial Cells and Human Amnion Mesenchymal Stem Cells.Zhongguo Shi Yan Xue Ye Xue Za Zhi.2015;23(4):1120-1124.
[20]Kwon A,Kim Y,Kim M,et al.Tissue-specific Differentiation Potency of Mesenchymal Stromal Cells from Perinatal Tissues.Sci Rep.2016;6:23544.
[21]Abumaree MH,Abomaray FM,Alshehri NA,et al.Phenotypic and Functional Characterization of Mesenchymal Stem/Multipotent Stromal Cells From Decidua Parietalis of Human Term Placenta.Reprod Sci.2016;23(9):1193-1207.
[22]Lobo SE,Leonel LC,Miranda CM,et al.The Placenta as an Organ and a Source of Stem Cells and Extracellular Matrix:AReview.Cells Tissues Organs.2016;201(4):239-252.
[23]James JL,Srinivasan S,Alexander M,et al.Can we fix it?Evaluating the potential of placental stem cells for the treatment of pregnancy disorders.Placenta.2014;35(2):77-84.
[24]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):315-317.
[25]Liu W,Xie Y,Gao T,et al.Reflection and observation:cell-based screening failing to detect HBV in HUMSCs derived from HBV-infected mothers underscores the importance of more stringent donor eligibility to reduce risk of transmission of infectious diseases for stem cell-based medical products.Stem Cell Res Ther.2018;9(1):177.
[26]Hong JQ,Gao Y,Song J,et al.Comparison of Biological Characteristics and Immunosuppressive Activity between Human Amniotic Mesenchymal Stem Cells and Human Bone Marrow Mesenchymal Stem Cells.Zhongguo Shi Yan Xue Ye Xue Za Zhi.2016;24(3):858-864.
[27]Yi JZ,Chen ZH,Xu FH,et al.Interferon-γsuppresses the proliferation and migration of human placenta-derived mesenchmal stromal cells and enhances their ability to induce the generation of CD4+CXCR5+Foxp3+Treg subset.Cell Immunol.2018;326:42-51.
[28]Zhu Y,Yang Y,Zhang Y,et al.Placental mesenchymal stem cells of fetal and maternal origins demonstrate different therapeutic potentials.Stem Cell Res Ther.2014;5(2):48.
[29]Ding C,Zou Q,Wang F,et al.Human amniotic mesenchymal stem cells improve ovarian function in natural aging through secreting hepatocyte growth factor and epidermal growth factor.Stem Cell Res Ther.2018;9(1):55.
[30]Beegle JR,Magner NL,Kalomoiris S,et al.Preclinical evaluation of mesenchymal stem cells overexpressing VEGF to treat critical limb ischemia.Mol Ther Methods Clin Dev.2016;3:16053.
[31]Liang L,Li Z,Ma T,et al.Transplantation of Human Placenta-Derived Mesenchymal Stem Cells Alleviates Critical Limb Ischemia in Diabetic Nude Rats.Cell Transplant.2017;26(1):45-61.
[32]Gan L,Duan H,Xu Q,et al.Human amniotic mesenchymal stromal cell transplantation improves endometrial regeneration in rodent models of intrauterine adhesions.Cytotherapy.2017;19(5):603-616.
[33]Li J,Yu Q,Huang H,et al.Human chorionic plate-derived mesenchymal stem cells transplantation restores ovarian function in a chemotherapy-induced mouse model of premature ovarian failure.Stem Cell Res Ther.2018;9(1):81.
[34]Fu Q,Man X,Yu M,et al.Human decidua mesenchymal stem cells regulate decidual natural killer cell function via interactions between collagen and leukocyte-associated immunoglobulinlike receptor 1.Mol Med Rep.2017;16(3):2791-2798.
[35]Kawai M,Rosen CJ.PPARγ:a circadian transcription factor in adipogenesis and osteogenesis.Nat Rev Endocrinol.2010;6(11):629-636.
[36]Ye L,Fan Z,Yu B,et al.Histone demethylases KDM4B and KDM6B promotes osteogenic differentiation of human MSCs.Cell Stem Cell.2012;11(1):50-61.
[37]Yamahara K,Harada K,Ohshima M,et al.Comparison of angiogenic,cytoprotective,and immunosuppressive properties of human amnion-and chorion-derived mesenchymal stem cells.PLoS One.2014;9(2):e88319.
[38]Pianta S,Bonassi Signoroni P,Muradore I,et al.Amniotic membrane mesenchymal cells-derived factors skew T cell polarization toward Treg and downregulate Th1 and Th17 cells subsets.Stem Cell Rev.2015;11(3):394-407.
[39]Ohshima M,Yamahara K,Ishikane S,et al.Systemic transplantation of allogenic fetal membrane-derived mesenchymal stem cells suppresses Th1 and Th17 T cell responses in experimental autoimmune myocarditis.J Mol Cell Cardiol.2012;53(3):420-428.
[40]Luz-Crawford P,Kurte M,Bravo-Alegría J,et al.Mesenchymal stem cells generate a CD4+CD25+Foxp3+regulatory T cell population during the differentiation process of Th1 and Th17cells.Stem Cell Res Ther.2013;4(3):65.
[41]Suzuki M,Jagger AL,Konya C,et al.CD8+CD45RA+CCR7+FOXP3+T cells with immunosuppressive properties:a novel subset of inducible human regulatory T cells.J Immunol.2012;189(5):2118-2130.
[42]Pelekanos RA,Sardesai VS,Futrega K,et al.Isolation and Expansion of Mesenchymal Stem/Stromal Cells Derived from Human Placenta Tissue.J Vis Exp.2016;(112):54204.
[2]Sardesai VS,Shafiee A,Fisk NM,et al.Avoidance of Maternal Cell Contamination and Overgrowth in Isolating Fetal Chorionic Villi Mesenchymal Stem Cells from Human Term Placenta.Stem Cells Transl Med.2017;6(4):1070-1084.
[3]Consentius C,Reinke P,Volk HD.Immunogenicity of allogeneic mesenchymal stromal cells:what has been seen in vitro and in vivo.Regen Med.2015;10(3):305-315.
[4]Bellavia M,Altomare R,Cacciabaudo F,et al.Towards an ideal source of mesenchymal stem cell isolation for possible therapeutic application in regenerative medicine.Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub.2014;158(3):356-360.
[5]Li M,Zhao Y,Hao H,et al.Mesenchymal stem cell-based therapy for nonhealing wounds:today and tomorrow.Wound Repair Regen.2015;23(4):465-482.
[6]Kim R,Park SI,Lee CY,et al.Alternative new mesenchymal stem cell source exerts tumor tropism through ALCAM and N-cadherin via regulation of microRNA-192 and-218.Mol Cell Biochem.2017;427(1-2):177-185.
[7]Ruan H,Xiao R,Jiang X,et al.Biofunctionalized self-assembly of peptide amphiphile induces the differentiation of bone marrow mesenchymal stem cells into neural cells.Mol Cell Biochem.2018 Jun 21.doi:10.1007/s11010-018-3386-9.[Epub ahead of print]
[8]Dezawa M.Muse Cells Provide the Pluripotency of Mesenchymal Stem Cells:Direct Contribution of Muse Cells to Tissue Regeneration.Cell Transplant.2016;25(5):849-861.
[9]Faghihi F,Mirzaei E,Ai J,et al.Erratum to:Differentiation Potential of Human Chorion-Derived Mesenchymal Stem Cells into Motor Neuron-Like Cells in Two-and Three-Dimensional Culture Systems.Mol Neurobiol.2016;53(3):1873.
[10]Wang X,Lazorchak AS,Song L,et al.Immune modulatory mesenchymal stem cells derived from human embryonic stem cells through a trophoblast-like stage.Stem Cells.2016;34(2):380-391.
[11]Valencia J,Blanco B,Yá?ez R,et al.Comparative analysis of the immunomodulatory capacities of human bone marrow-and adipose tissue-derived mesenchymal stromal cells from the same donor.Cytotherapy.2016;18(10):1297-1311.
[12]Lim JY,Im KI,Lee ES,et al.Enhanced immunoregulation of mesenchymal stem cells by IL-10-producing type 1 regulatory T cells in collagen-induced arthritis.Sci Rep.2016;6:26851.
[13]Ma OK,Chan KH.Immunomodulation by mesenchymal stem cells:Interplay between mesenchymal stem cells and regulatory lymphocytes.World J Stem Cells.2016;8(9):268-278.
[14]Wu M,Zhang R,Zou Q,et al.Comparison of the Biological Characteristics of Mesenchymal Stem Cells Derived from the Human Placenta and Umbilical Cord.Sci Rep.2018;8(1):5014.
[15]Timmins NE,Kiel M,Günther M,et al.Closed system isolation and scalable expansion of human placental mesenchymal stem cells.Biotechnol Bioeng.2012;109(7):1817-1826.
[16]Du L,Lv R,Yang X,et al.Hypoxic conditioned medium of placenta-derived mesenchymal stem cells protects against scar formation.Life Sci.2016;149:51-57.
[17]Araújo AB,Salton GD,Furlan JM,et al.Comparison of human mesenchymal stromal cells from four neonatal tissues:Amniotic membrane,chorionic membrane,placental decidua and umbilical cord.Cytotherapy.2017;19(5):577-585.
[18]Eidem HR,Ackerman WE 4th,McGary KL,et al.Gestational tissue transcriptomics in term and preterm human pregnancies:a systematic review and meta-analysis.BMC Med Genomics.2015;8:27.
[19]Gan WT,Sun X,Lu Y.Comparison of Biological Characteristics between Human Amnion Epithelial Cells and Human Amnion Mesenchymal Stem Cells.Zhongguo Shi Yan Xue Ye Xue Za Zhi.2015;23(4):1120-1124.
[20]Kwon A,Kim Y,Kim M,et al.Tissue-specific Differentiation Potency of Mesenchymal Stromal Cells from Perinatal Tissues.Sci Rep.2016;6:23544.
[21]Abumaree MH,Abomaray FM,Alshehri NA,et al.Phenotypic and Functional Characterization of Mesenchymal Stem/Multipotent Stromal Cells From Decidua Parietalis of Human Term Placenta.Reprod Sci.2016;23(9):1193-1207.
[22]Lobo SE,Leonel LC,Miranda CM,et al.The Placenta as an Organ and a Source of Stem Cells and Extracellular Matrix:AReview.Cells Tissues Organs.2016;201(4):239-252.
[23]James JL,Srinivasan S,Alexander M,et al.Can we fix it?Evaluating the potential of placental stem cells for the treatment of pregnancy disorders.Placenta.2014;35(2):77-84.
[24]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):315-317.
[25]Liu W,Xie Y,Gao T,et al.Reflection and observation:cell-based screening failing to detect HBV in HUMSCs derived from HBV-infected mothers underscores the importance of more stringent donor eligibility to reduce risk of transmission of infectious diseases for stem cell-based medical products.Stem Cell Res Ther.2018;9(1):177.
[26]Hong JQ,Gao Y,Song J,et al.Comparison of Biological Characteristics and Immunosuppressive Activity between Human Amniotic Mesenchymal Stem Cells and Human Bone Marrow Mesenchymal Stem Cells.Zhongguo Shi Yan Xue Ye Xue Za Zhi.2016;24(3):858-864.
[27]Yi JZ,Chen ZH,Xu FH,et al.Interferon-γsuppresses the proliferation and migration of human placenta-derived mesenchmal stromal cells and enhances their ability to induce the generation of CD4+CXCR5+Foxp3+Treg subset.Cell Immunol.2018;326:42-51.
[28]Zhu Y,Yang Y,Zhang Y,et al.Placental mesenchymal stem cells of fetal and maternal origins demonstrate different therapeutic potentials.Stem Cell Res Ther.2014;5(2):48.
[29]Ding C,Zou Q,Wang F,et al.Human amniotic mesenchymal stem cells improve ovarian function in natural aging through secreting hepatocyte growth factor and epidermal growth factor.Stem Cell Res Ther.2018;9(1):55.
[30]Beegle JR,Magner NL,Kalomoiris S,et al.Preclinical evaluation of mesenchymal stem cells overexpressing VEGF to treat critical limb ischemia.Mol Ther Methods Clin Dev.2016;3:16053.
[31]Liang L,Li Z,Ma T,et al.Transplantation of Human Placenta-Derived Mesenchymal Stem Cells Alleviates Critical Limb Ischemia in Diabetic Nude Rats.Cell Transplant.2017;26(1):45-61.
[32]Gan L,Duan H,Xu Q,et al.Human amniotic mesenchymal stromal cell transplantation improves endometrial regeneration in rodent models of intrauterine adhesions.Cytotherapy.2017;19(5):603-616.
[33]Li J,Yu Q,Huang H,et al.Human chorionic plate-derived mesenchymal stem cells transplantation restores ovarian function in a chemotherapy-induced mouse model of premature ovarian failure.Stem Cell Res Ther.2018;9(1):81.
[34]Fu Q,Man X,Yu M,et al.Human decidua mesenchymal stem cells regulate decidual natural killer cell function via interactions between collagen and leukocyte-associated immunoglobulinlike receptor 1.Mol Med Rep.2017;16(3):2791-2798.
[35]Kawai M,Rosen CJ.PPARγ:a circadian transcription factor in adipogenesis and osteogenesis.Nat Rev Endocrinol.2010;6(11):629-636.
[36]Ye L,Fan Z,Yu B,et al.Histone demethylases KDM4B and KDM6B promotes osteogenic differentiation of human MSCs.Cell Stem Cell.2012;11(1):50-61.
[37]Yamahara K,Harada K,Ohshima M,et al.Comparison of angiogenic,cytoprotective,and immunosuppressive properties of human amnion-and chorion-derived mesenchymal stem cells.PLoS One.2014;9(2):e88319.
[38]Pianta S,Bonassi Signoroni P,Muradore I,et al.Amniotic membrane mesenchymal cells-derived factors skew T cell polarization toward Treg and downregulate Th1 and Th17 cells subsets.Stem Cell Rev.2015;11(3):394-407.
[39]Ohshima M,Yamahara K,Ishikane S,et al.Systemic transplantation of allogenic fetal membrane-derived mesenchymal stem cells suppresses Th1 and Th17 T cell responses in experimental autoimmune myocarditis.J Mol Cell Cardiol.2012;53(3):420-428.
[40]Luz-Crawford P,Kurte M,Bravo-Alegría J,et al.Mesenchymal stem cells generate a CD4+CD25+Foxp3+regulatory T cell population during the differentiation process of Th1 and Th17cells.Stem Cell Res Ther.2013;4(3):65.
[41]Suzuki M,Jagger AL,Konya C,et al.CD8+CD45RA+CCR7+FOXP3+T cells with immunosuppressive properties:a novel subset of inducible human regulatory T cells.J Immunol.2012;189(5):2118-2130.
[42]Pelekanos RA,Sardesai VS,Futrega K,et al.Isolation and Expansion of Mesenchymal Stem/Stromal Cells Derived from Human Placenta Tissue.J Vis Exp.2016;(112):54204.