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  1. Article: Editorial: Adult stem cells for regenerative medicine: From cell fate to clinical applications.

    Li, Jingting / Luanpitpong, Sudjit / Kheolamai, Pakpoom

    Frontiers in cell and developmental biology

    2022  Volume 10, Page(s) 1069665

    Language English
    Publishing date 2022-10-31
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2022.1069665
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Generation and Functional Characterization of Anti-CD19 Chimeric Antigen Receptor-Natural Killer Cells from Human Induced Pluripotent Stem Cells.

    Klaihmon, Phatchanat / Kang, Xing / Issaragrisil, Surapol / Luanpitpong, Sudjit

    International journal of molecular sciences

    2023  Volume 24, Issue 13

    Abstract: Natural killer (NK) cells are a part of innate immunity that can be activated rapidly in response to malignant transformed cells without prior sensitization. Engineering NK cells to express chimeric antigen receptors (CARs) allows them to be directed ... ...

    Abstract Natural killer (NK) cells are a part of innate immunity that can be activated rapidly in response to malignant transformed cells without prior sensitization. Engineering NK cells to express chimeric antigen receptors (CARs) allows them to be directed against corresponding target tumor antigens. CAR-NK cells are regarded as a promising candidate for cellular immunotherapy alternatives to conventional CAR-T cells, due to the relatively low risk of graft-versus-host disease and safer clinical profile. Human induced pluripotent stem cells (iPSCs) are a promising renewable cell source of clinical NK cells. In the present study, we successfully introduced a third-generation CAR targeting CD19, which was validated to have effective signaling domains suitable for NK cells, into umbilical cord blood NK-derived iPSCs, followed by a single-cell clone selection and thorough iPSC characterization. The established single-cell clone of CAR19-NK/iPSCs, which is highly desirable for clinical application, can be differentiated using serum- and feeder-free protocols into functional CAR19-iNK-like cells with improved anti-tumor activity against CD19-positive hematologic cancer cells when compared with wild-type (WT)-iNK-like cells. With the feasibility of being an alternative source for off-the-shelf CAR-NK cells, a library of single-cell clones of CAR-engineered NK/iPSCs targeting different tumor antigens may be created for future clinical application.
    MeSH term(s) Humans ; Receptors, Chimeric Antigen/genetics ; Induced Pluripotent Stem Cells ; Immunotherapy, Adoptive ; Killer Cells, Natural ; Antigens, Neoplasm
    Chemical Substances Receptors, Chimeric Antigen ; Antigens, Neoplasm
    Language English
    Publishing date 2023-06-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms241310508
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Anti-TIM3 chimeric antigen receptor-natural killer cells from engineered induced pluripotent stem cells effectively target acute myeloid leukemia cells.

    Klaihmon, Phatchanat / Luanpitpong, Sudjit / Kang, Xing / Issaragrisil, Surapol

    Cancer cell international

    2023  Volume 23, Issue 1, Page(s) 297

    Abstract: Background: Acute myeloid leukemia (AML) is a clonal malignant disorder which originates from a small number of leukemia-initiating cells or leukemic stem cells (LSCs)-the subpopulation that is also the root cause of relapsed/refractory AML. Chimeric ... ...

    Abstract Background: Acute myeloid leukemia (AML) is a clonal malignant disorder which originates from a small number of leukemia-initiating cells or leukemic stem cells (LSCs)-the subpopulation that is also the root cause of relapsed/refractory AML. Chimeric antigen receptor (CAR)-T cell therapy has proved successful at combating certain hematologic malignancies, but has several hurdles that limit its widespread applications. CAR-natural killer (NK) cells do not carry the risk of inducing graft-versus-host disease (GvHD) frequently associated with allogeneic T cells, thereby overcoming time-consuming, autologous cell manufacturing, and have relatively safer clinical profiles than CAR-T cells. The present study aimed to generate anti-TIM3 CAR-NK cells targeting LSCs from a clonal master induced pluripotent stem cells engineered with the third-generation anti-TIM3 CAR.
    Methods: A clonal master umbilical cord blood NK-derived induced pluripotent stem cell (iPSC) line, MUSIi013-A, was used as a starting cells for engineering of an anti-TIM3 CAR harboring TIM3 scFv fragment (clone TSR-022), CD28, 4-1BB, and CD3ζ signaling (CAR-TIM3). The established CAR-TIM3 iPSCs were further differentiated under serum- and feeder-free conditions into functional CAR-TIM3 NK cells and tested for its anti-tumor activity against various TIM3-positive AML cells.
    Results: We successfully established a single-cell clone of CAR-TIM3 iPSCs, as validated by genomic DNA sequencing as well as antibody and antigen-specific detection. We performed thorough iPSC characterization to confirm its retained pluripotency and differentiation capacity. The established CAR-TIM3 iPSCs can be differentiated into CAR-TIM3 NK-like cells, which were further proven to have enhanced anti-tumor activity against TIM3-positive AML cells with minimal effect on TIM3-negative cells when compared with wild-type (WT) NK-like cells from parental iPSCs.
    Conclusions: iPSCs engineered with CARs, including the established single-cell clone CAR-TIM3 iPSCs herein, are potential alternative cell source for generating off-the-shelf CAR-NK cells as well as other CAR-immune cells. The feasibility of differentiation of functional CAR-TIM3 NK cells under serum- and feeder-free conditions support that Good Manufacturing Practice (GMP)-compliant protocols can be further established for future clinical applications.
    Language English
    Publishing date 2023-11-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 2091573-1
    ISSN 1475-2867
    ISSN 1475-2867
    DOI 10.1186/s12935-023-03153-9
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  4. Article ; Online: Generation and Functional Characterization of Anti-CD19 Chimeric Antigen Receptor-Natural Killer Cells from Human Induced Pluripotent Stem Cells

    Phatchanat Klaihmon / Xing Kang / Surapol Issaragrisil / Sudjit Luanpitpong

    International Journal of Molecular Sciences, Vol 24, Iss 10508, p

    2023  Volume 10508

    Abstract: Natural killer (NK) cells are a part of innate immunity that can be activated rapidly in response to malignant transformed cells without prior sensitization. Engineering NK cells to express chimeric antigen receptors (CARs) allows them to be directed ... ...

    Abstract Natural killer (NK) cells are a part of innate immunity that can be activated rapidly in response to malignant transformed cells without prior sensitization. Engineering NK cells to express chimeric antigen receptors (CARs) allows them to be directed against corresponding target tumor antigens. CAR-NK cells are regarded as a promising candidate for cellular immunotherapy alternatives to conventional CAR-T cells, due to the relatively low risk of graft-versus-host disease and safer clinical profile. Human induced pluripotent stem cells (iPSCs) are a promising renewable cell source of clinical NK cells. In the present study, we successfully introduced a third-generation CAR targeting CD19, which was validated to have effective signaling domains suitable for NK cells, into umbilical cord blood NK-derived iPSCs, followed by a single-cell clone selection and thorough iPSC characterization. The established single-cell clone of CAR19-NK/iPSCs, which is highly desirable for clinical application, can be differentiated using serum- and feeder-free protocols into functional CAR19-iNK-like cells with improved anti-tumor activity against CD19-positive hematologic cancer cells when compared with wild-type (WT)-iNK-like cells. With the feasibility of being an alternative source for off-the-shelf CAR-NK cells, a library of single-cell clones of CAR-engineered NK/iPSCs targeting different tumor antigens may be created for future clinical application.
    Keywords chimeric antigen receptor ; induced pluripotent stem cell ; natural killer cell ; anti-CD19 CAR ; leukemia ; CAR-NK ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Editorial

    Jingting Li / Sudjit Luanpitpong / Pakpoom Kheolamai

    Frontiers in Cell and Developmental Biology, Vol

    Adult stem cells for regenerative medicine: From cell fate to clinical applications

    2022  Volume 10

    Keywords stem cells ; regenerative medicine ; mesenchymal stem cells ; bone marrow mesenchymal stem cells ; dental pulp stem cells ; limbal stem cells ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2022-10-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article: A novel E-cadherin/SOX9 axis regulates cancer stem cells in multiple myeloma by activating Akt and MAPK pathways.

    Samart, Parinya / Rojanasakul, Yon / Issaragrisil, Surapol / Luanpitpong, Sudjit

    Experimental hematology & oncology

    2022  Volume 11, Issue 1, Page(s) 41

    Abstract: Cancer stem cells (CSCs) have been identified in multiple myeloma (MM) and are widely regarded as a key driver of MM initiation and progression. E-cadherin, in addition to its established role as a marker for epithelial-mesenchymal transition, also plays ...

    Abstract Cancer stem cells (CSCs) have been identified in multiple myeloma (MM) and are widely regarded as a key driver of MM initiation and progression. E-cadherin, in addition to its established role as a marker for epithelial-mesenchymal transition, also plays critical roles in controlling the aggressive behaviors of various tumor cells. Here, we show that depletion of E-cadherin in MM cells remarkably inhibited cell proliferation and cell cycle progression, in part through the decreased prosurvival CD138 and Bcl-2 and the inactivated Akt and MAPK pathways. CSC features, including the ability of the cells to form clonogenic colonies indicative of self-renewal and side population, were greatly suppressed upon the depletion of E-cadherin and subsequent loss of SOX9 stem-cell factor. We further provide evidence that SOX9 is a downstream target of E-cadherin-mediated CSC growth and self-renewal-ectopic re-expression of SOX9 in E-cadherin-depleted cells rescued its inhibitory effects on CSC-like properties and survival signaling. Collectively, our findings unveil a novel regulatory mechanism of MM CSCs via the E-cadherin/SOX9 axis, which could be important in understanding the long-term cell survival and outgrowth that leads to relapsed/refractory MM.
    Language English
    Publishing date 2022-07-13
    Publishing country England
    Document type Letter
    ZDB-ID 2669066-4
    ISSN 2162-3619
    ISSN 2162-3619
    DOI 10.1186/s40164-022-00294-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Correction: Metabolic sensor O-GlcNAcylation regulates erythroid differentiation and globin production via BCL11A.

    Luanpitpong, Sudjit / Kang, Xing / Janan, Montira / Thumanu, Kanjana / Li, Jingting / Kheolamai, Pakpoom / Issaragrisil, Surapol

    Stem cell research & therapy

    2022  Volume 13, Issue 1, Page(s) 396

    Language English
    Publishing date 2022-08-03
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2548671-8
    ISSN 1757-6512 ; 1757-6512
    ISSN (online) 1757-6512
    ISSN 1757-6512
    DOI 10.1186/s13287-022-03098-2
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  8. Article: Musashi-2 in cancer-associated fibroblasts promotes non-small cell lung cancer metastasis through paracrine IL-6-driven epithelial-mesenchymal transition.

    Samart, Parinya / Heenatigala Palliyage, Gayathri / Issaragrisil, Surapol / Luanpitpong, Sudjit / Rojanasakul, Yon

    Cell & bioscience

    2023  Volume 13, Issue 1, Page(s) 205

    Abstract: Background: Lung cancer, the most common cause of cancer-related mortality worldwide, is predominantly associated with advanced/metastatic disease. The interaction between tumor cells and cancer-associated fibroblasts (CAFs) in tumor microenvironment is ...

    Abstract Background: Lung cancer, the most common cause of cancer-related mortality worldwide, is predominantly associated with advanced/metastatic disease. The interaction between tumor cells and cancer-associated fibroblasts (CAFs) in tumor microenvironment is known to be essential for regulating tumor progression and metastasis, but the underlying mechanisms, particularly the role of RNA-binding protein Musashi-2 (MSI2) in CAFs in promoting non-small cell lung cancer (NSCLC) invasiveness and metastatic spread, remain obscure.
    Methods: Genomic and proteomic database analyses were performed to evaluate the potential clinical significance of MSI2 in NSCLC tumor and stromal clinical specimens. Molecular approaches were used to modify MSI2 in CAFs and determine its functional role in NSCLC cell motility in vitro using 2D and 3D models, and in metastasis in a xenograft mouse model using live-cell imaging.
    Results: MSI2, both gene and protein, is upregulated in NSCLC tissues and is associated with poor prognosis and high metastatic risk in patients. Interestingly, MSI2 is also upregulated in NSCLC stroma and activated fibroblasts, including CAFs. Depletion of MSI2 in CAFs by CRISPR-Cas9 strongly inhibits NSCLC cell migration and invasion in vitro, and attenuates local and distant metastatic spread of NSCLC cells in vivo. The crosstalk between CAFs and NSCLC cells occurs via paracrine signaling, which is regulated by MSI2 in CAFs via IL-6. The secreted IL-6 promotes epithelial-mesenchymal transition in NSCLC cells, which drives metastasis.
    Conclusion: Our findings reveal for the first time that MSI2 in CAFs is important in CAF-mediated NSCLC cell invasiveness and metastasis via IL-6 paracrine signaling. Therefore, targeting the MSI2/IL-6 axis in CAFs could be effective in combating NSCLC metastasis.
    Language English
    Publishing date 2023-11-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 2593367-X
    ISSN 2045-3701
    ISSN 2045-3701
    DOI 10.1186/s13578-023-01158-5
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  9. Article ; Online: O-GlcNAcylation homeostasis controlled by calcium influx channels regulates multiple myeloma dissemination.

    Samart, Parinya / Luanpitpong, Sudjit / Rojanasakul, Yon / Issaragrisil, Surapol

    Journal of experimental & clinical cancer research : CR

    2021  Volume 40, Issue 1, Page(s) 100

    Abstract: Background: Multiple myeloma (MM) cell motility is a critical step during MM dissemination throughout the body, but how it is regulated remains largely unknown. As hypercalcemia is an important clinical feature of MM, high calcium (Ca: Methods: ... ...

    Abstract Background: Multiple myeloma (MM) cell motility is a critical step during MM dissemination throughout the body, but how it is regulated remains largely unknown. As hypercalcemia is an important clinical feature of MM, high calcium (Ca
    Methods: Bioinformatics analyses were employed to assess the clinical significance of Ca
    Results: Inhibition of TRPM7, ORAI1, and STIM1 influx channels, which are highly expressed in MM patients, and subsequent blockage of Ca
    Conclusions: Our findings unveil a novel regulatory mechanism of MM cell motility via Ca
    MeSH term(s) Animals ; Calcium Channels/metabolism ; Homeostasis/genetics ; Humans ; Male ; Mice ; Multiple Myeloma/genetics ; N-Acetylglucosaminyltransferases/metabolism ; Transfection
    Chemical Substances Calcium Channels ; N-Acetylglucosaminyltransferases (EC 2.4.1.-)
    Language English
    Publishing date 2021-03-16
    Publishing country England
    Document type Journal Article
    ZDB-ID 803138-1
    ISSN 1756-9966 ; 0392-9078
    ISSN (online) 1756-9966
    ISSN 0392-9078
    DOI 10.1186/s13046-021-01876-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Distinctive Roles of YAP and TAZ in Human Endothelial Progenitor Cells Growth and Functions.

    Klaihmon, Phatchanat / Lorthongpanich, Chanchao / Kheolamai, Pakpoom / Luanpitpong, Sudjit / Issaragrisil, Surapol

    Biomedicines

    2022  Volume 10, Issue 1

    Abstract: The hippo signaling pathway plays an essential role in controlling organ size and balancing tissue homeostasis. Its two main effectors, yes-associated protein (YAP) and WW domain-containing transcription regulator 1, WWTR1 or TAZ, have also been shown to ...

    Abstract The hippo signaling pathway plays an essential role in controlling organ size and balancing tissue homeostasis. Its two main effectors, yes-associated protein (YAP) and WW domain-containing transcription regulator 1, WWTR1 or TAZ, have also been shown to regulate endothelial cell functions and angiogenesis. In this study, the functions of YAP and TAZ in human endothelial progenitor cells (EPCs) were investigated by a loss-of-function study using CRISPR/Cas9-mediated gene knockdown (KD). Depletion of either YAP or TAZ reduced EPC survival and impaired many of their critical functions, including migration, invasion, vessel-formation, and expression of pro-angiogenic genes. Notably, TAZ-KD EPCs exhibited more severe phenotypes in comparison to YAP-KD EPCs. Moreover, the conditioned medium derived from TAZ-KD EPCs reduced the survivability of human lung cancer cells and increased their sensitivity to chemotherapeutic agents. The overexpression of either wild-type or constitutively active TAZ rescued the impaired phenotypes of TAZ-KD EPCs and restored the expression of pro-angiogenic genes in those EPCs. In summary, we demonstrate the crucial role of Hippo signaling components, YAP and TAZ, in controlling several aspects of EPC functions that can potentially be used as a drug target to enhance EPC functions in patients.
    Language English
    Publishing date 2022-01-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines10010147
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