Rat bone marrow-derived mesenchymal stem cells were cultured and passaged in vitro. After induction with basic fibroblast growth factor for 24 hours, passage 3 bone marrow-derived mesenchymal stem cells were additiona...Rat bone marrow-derived mesenchymal stem cells were cultured and passaged in vitro. After induction with basic fibroblast growth factor for 24 hours, passage 3 bone marrow-derived mesenchymal stem cells were additionally induced into dopaminergic neurons using three different combinations with basic fibroblast growth factor as follows： 20% Xiangdan injection; ali-trans retinoic acid ＋ glial-derived neurotrophic factor; or sonic hedgehog ＋ fibroblast growth factor 8. Results suggest that the bone marrow-derived mesenchymal stem cells showed typical neuronal morphological characteristics after induction. In particular, after treatment with sonic hedgehog ＋ fibroblast growth factor 8, the expressions of nestin, neuron-specific enolase, microtubule- associated protein 2, tyrosine hydroxylase and vesicular monoamine transporter-2 in cells were significantly increased. Moreover, the levels of catecholamines in the culture supernatant were significantly increased. These findings indicate that Xiangdan injection, all-trans retinoic acid ＋ glial-derived neurotrophic factor, and sonic hedgehog ＋ fibroblast growth factor 8 can all induce dopaminergic neuronal differentiation from bone marrow-derived mesenchymal stem cells. In particular, the efficiency of sonic hedgehog ＋ fibroblast growth factor 8 was highest.展开更多
Numerous efforts have been attempted to regenerate T cells in culture dish from pluripotent stem cells(PSCs).However,in vitro generated T cells exhibited extremely low activity and compromised immunocompetency in vivo...Numerous efforts have been attempted to regenerate T cells in culture dish from pluripotent stem cells(PSCs).However,in vitro generated T cells exhibited extremely low activity and compromised immunocompetency in vivo.Here,we describe a two-step protocol for regenerating functional T cells using an inducible Runx1-Hoxa9-PSC(iR9-PSCs)line.The procedure mainly includes generation of induced hematopoietic progenitor cells(iHPCs)in vitro,transplantation,and development of functional induced T cells(iT)in vivo via transplantation.The entire induction process in vitro requires 21 days before iHPCs transplantation.The development of mature T cells in vivo takes 4 to 6 weeks post-transplantation.We provide a simple and reproducible approach for functional T cell regeneration from iR9-PSCs for research purpose.展开更多
In patients with autoimmune diseases,psychological comorbidities,including anxiety,depression and cognitive dysfunction,often occur.1 Anxiety and depression in these patients not only cause a significant disease burde...In patients with autoimmune diseases,psychological comorbidities,including anxiety,depression and cognitive dysfunction,often occur.1 Anxiety and depression in these patients not only cause a significant disease burden1 but also might prevent effective treatment through the neuro-immune axis.2 The latter issue results in disease aggravation and,in turn,adversely impacts psychological and social wellbeing.Therefore,effective treatment is required to break the vicious feedforward cycle of physical–psychological interactions.展开更多
Chimeric antigen receptor T cell(CAR-T)therapy is one of the most promising approaches in cancer treatment.1 However,the limited availability of patient-derived T cells narrows its universal applicability.Thus,it is n...Chimeric antigen receptor T cell(CAR-T)therapy is one of the most promising approaches in cancer treatment.1 However,the limited availability of patient-derived T cells narrows its universal applicability.Thus,it is necessary to invent new methods to obtain alternative T-cell sources.Pluripotent stem cells(PSCs),which have unlimited culture potential and are amenable to gene editing,are ideal for generating induced T(iT)cells.展开更多
基金supported by the Scientific Research Foundation for the Returned Overseas, No. [2009]1001the Natural Science Foundation of Shandong Province, No.Y2008C129
文摘Rat bone marrow-derived mesenchymal stem cells were cultured and passaged in vitro. After induction with basic fibroblast growth factor for 24 hours, passage 3 bone marrow-derived mesenchymal stem cells were additionally induced into dopaminergic neurons using three different combinations with basic fibroblast growth factor as follows： 20% Xiangdan injection; ali-trans retinoic acid ＋ glial-derived neurotrophic factor; or sonic hedgehog ＋ fibroblast growth factor 8. Results suggest that the bone marrow-derived mesenchymal stem cells showed typical neuronal morphological characteristics after induction. In particular, after treatment with sonic hedgehog ＋ fibroblast growth factor 8, the expressions of nestin, neuron-specific enolase, microtubule- associated protein 2, tyrosine hydroxylase and vesicular monoamine transporter-2 in cells were significantly increased. Moreover, the levels of catecholamines in the culture supernatant were significantly increased. These findings indicate that Xiangdan injection, all-trans retinoic acid ＋ glial-derived neurotrophic factor, and sonic hedgehog ＋ fibroblast growth factor 8 can all induce dopaminergic neuronal differentiation from bone marrow-derived mesenchymal stem cells. In particular, the efficiency of sonic hedgehog ＋ fibroblast growth factor 8 was highest.
基金This work was supported by grants from the Strategic Priority Research Program of Chinese Academy of Sciences(XDA16010601)the Health and Medical Care Collaborative Innovation Program of Guangzhou Scientific and Technology(201803040017)+4 种基金the CAS Key Research Program of Frontier Sciences(QYZDB-SSW-SMC057)the National Key R&D Program of China(2019YFA0110200)the Major Research and Development Project of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR110104006)the Science and Technology Planning Project of Guangdong Province(2017B030314056)the grants from the National Natural Science Foundation of China(Grant No 81925002).
文摘Numerous efforts have been attempted to regenerate T cells in culture dish from pluripotent stem cells(PSCs).However,in vitro generated T cells exhibited extremely low activity and compromised immunocompetency in vivo.Here,we describe a two-step protocol for regenerating functional T cells using an inducible Runx1-Hoxa9-PSC(iR9-PSCs)line.The procedure mainly includes generation of induced hematopoietic progenitor cells(iHPCs)in vitro,transplantation,and development of functional induced T cells(iT)in vivo via transplantation.The entire induction process in vitro requires 21 days before iHPCs transplantation.The development of mature T cells in vivo takes 4 to 6 weeks post-transplantation.We provide a simple and reproducible approach for functional T cell regeneration from iR9-PSCs for research purpose.
基金supported by the National Natural Science Foundation of China(No.81701042 to C.L.,Nos.81974553 and 81800187 to W.S.)the Youth Innovation Team of Shandong Provincial Department of Education(No.2019KJK002 to W.S.)the Taishan Scholars Program of Shandong Province and Bellberry-Viertel Senior Medical Research Fellowship(D.Y.).
文摘In patients with autoimmune diseases,psychological comorbidities,including anxiety,depression and cognitive dysfunction,often occur.1 Anxiety and depression in these patients not only cause a significant disease burden1 but also might prevent effective treatment through the neuro-immune axis.2 The latter issue results in disease aggravation and,in turn,adversely impacts psychological and social wellbeing.Therefore,effective treatment is required to break the vicious feedforward cycle of physical–psychological interactions.
基金supported by the CAS Key Research Program of Frontier Sciences(QYZDB-SSW-SMC057)the Strategic Priority Research Program of Chinese Academy of Sciences(XDA16010601)+4 种基金the National Key R&D Program of China(2019YFA0110203)the Major Research and Development Project of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR110104006)the Health and Medical Care Collaborative Innovation Program of Guangzhou Scientific and Technology(201803040017)the Science and Technology Planning Project of Guangdong Province(2017B030314056)the National Natural Science Foundation of China(81925002,81970099,31900814).
文摘Chimeric antigen receptor T cell(CAR-T)therapy is one of the most promising approaches in cancer treatment.1 However,the limited availability of patient-derived T cells narrows its universal applicability.Thus,it is necessary to invent new methods to obtain alternative T-cell sources.Pluripotent stem cells(PSCs),which have unlimited culture potential and are amenable to gene editing,are ideal for generating induced T(iT)cells.
