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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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Article ; Online: Role of YAP as a Mechanosensing Molecule in Stem Cells and Stem Cell-Derived Hematopoietic Cells

Nattaya Damkham / Surapol Issaragrisil / Chanchao Lorthongpanich

International Journal of Molecular Sciences, Vol 23, Iss 14634, p

2022 Volume 14634

Abstract: Yes-associated protein (YAP) and WW domain-containing transcription regulator protein 1 (WWTR1, also known as TAZ) are transcriptional coactivators in the Hippo signaling pathway. Both are well-known regulators of cell proliferation and organ size ... ...

Abstract	Yes-associated protein (YAP) and WW domain-containing transcription regulator protein 1 (WWTR1, also known as TAZ) are transcriptional coactivators in the Hippo signaling pathway. Both are well-known regulators of cell proliferation and organ size control, and they have significant roles in promoting cell proliferation and differentiation. The roles of YAP and TAZ in stem cell pluripotency and differentiation have been extensively studied. However, the upstream mediators of YAP and TAZ are not well understood. Recently, a novel role of YAP in mechanosensing and mechanotransduction has been reported. The present review updates information on the regulation of YAP by mechanical cues such as extracellular matrix stiffness, fluid shear stress, and actin cytoskeleton tension in stem cell behaviors and differentiation. The review explores mesenchymal stem cell fate decisions, pluripotent stem cells (PSCs), self-renewal, pluripotency, and differentiation to blood products. Understanding how cells sense their microenvironment or niche and mimic those microenvironments in vitro could improve the efficiency of producing stem cell products and the efficacy of the products.
Keywords	YAP ; stem cells ; differentiation ; hematopoietic stem cells ; mechanical forces ; mechanosensing ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	571
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Distinctive Roles of YAP and TAZ in Human Endothelial Progenitor Cells Growth and Functions

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

Biomedicines, Vol 10, Iss 147, p

2022 Volume 147

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.
Keywords	hippo signaling pathway ; endothelial progenitor cells ; YAP/TAZ ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Induced Pluripotent Stem Cells as a Tool for Modeling Hematologic Disorders and as a Potential Source for Cell-Based Therapies

Ponthip Pratumkaew / Surapol Issaragrisil / Sudjit Luanpitpong

Cells, Vol 10, Iss 3250, p

2021 Volume 3250

Abstract: The breakthrough in human induced pluripotent stem cells (hiPSCs) has revolutionized the field of biomedical and pharmaceutical research and opened up vast opportunities for drug discovery and regenerative medicine, especially when combined with gene- ... ...

Abstract	The breakthrough in human induced pluripotent stem cells (hiPSCs) has revolutionized the field of biomedical and pharmaceutical research and opened up vast opportunities for drug discovery and regenerative medicine, especially when combined with gene-editing technology. Numerous healthy and patient-derived hiPSCs for human disease modeling have been established, enabling mechanistic studies of pathogenesis, platforms for preclinical drug screening, and the development of novel therapeutic targets/approaches. Additionally, hiPSCs hold great promise for cell-based therapy, serving as an attractive cell source for generating stem/progenitor cells or functional differentiated cells for degenerative diseases, due to their unlimited proliferative capacity, pluripotency, and ethical acceptability. In this review, we provide an overview of hiPSCs and their utility in the study of hematologic disorders through hematopoietic differentiation. We highlight recent hereditary and acquired genetic hematologic disease modeling with patient-specific iPSCs, and discuss their applications as instrumental drug screening tools. The clinical applications of hiPSCs in cell-based therapy, including the next-generation cancer immunotherapy, are provided. Lastly, we discuss the current challenges that need to be addressed to fulfill the validity of hiPSC-based disease modeling and future perspectives of hiPSCs in the field of hematology.
Keywords	induced pluripotent stem cells ; disease modeling ; blood disorders ; genetic disorders ; cell-based therapy ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Musashi-2 in cancer-associated fibroblasts promotes non-small cell lung cancer metastasis through paracrine IL-6-driven epithelial-mesenchymal transition

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

Cell & Bioscience, Vol 13, Iss 1, Pp 1-

2023 Volume 18

Abstract: 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 ... ...

Abstract	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.
Keywords	Musashi-2 ; Tumor microenvironment ; Cancer-associated fibroblast ; Non-small cell lung cancer ; Metastasis ; IL-6 ; Biotechnology ; TP248.13-248.65 ; Biology (General) ; QH301-705.5 ; Biochemistry ; QD415-436
Subject code	610
Language	English
Publishing date	2023-11-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Post-Transplant Cyclophosphamide and Thymoglobulin, a Graft-Versus-Host Disease Prophylaxis in Matched Sibling Donor Peripheral Blood Stem Cell Transplantations

Chutima Kunacheewa / Weerapat Owattanapanish / Chutirat Jirabanditsakul / Surapol Issaragrisil

Cell Transplantation, Vol

2020 Volume 29

Abstract: Post-transplant cyclophosphamide (PTCy) has been explored in several types of stem cell transplantations (SCTs) and it proved highly effective in controlling graft-versus-host disease (GvHD) without aggravating relapsed disease. However, PTCy alone has ... ...

Abstract	Post-transplant cyclophosphamide (PTCy) has been explored in several types of stem cell transplantations (SCTs) and it proved highly effective in controlling graft-versus-host disease (GvHD) without aggravating relapsed disease. However, PTCy alone has resulted in inferior outcomes in matched sibling donor (MSD) employing peripheral blood (PB) SCTs. We hypothesized that adding thymoglobulin to PTCy would be able to control GvHD effectively. We retrospectively compared the use of standard GvHD prophylaxis encompassing a combination of PTCy and thymoglobulin (ATG) in patients with myeloid malignancies in a myeloablative conditioning MSD PBSCT. Forty-two patients underwent PBSCT using either methotrexate and cyclosporine (MTX/CSA, 21 patients) or PTCy and ATG (21 patients) as a GvHD prophylaxis. With median follow-ups of 71 months, the 1-year GvHD-free, relapse-free survival rates and chronic GvHD-free survival rate of the standard and PTCy/ATG groups were similar: 24% versus 37% ( P = 0.251) and 29% versus 43% ( P = 0.095), respectively. When focusing on chronic GvHD we observed that 17/35 patients (48.6%) suffered from this, 5/18 (27.8%) treated with MTX/CSA had extensive chronic GvHD, but 0/17 PTCy/ATG did. Twenty-one patients required additional GvHD treatment; 7/21 in the PTCy/ATG received only corticosteroid, while 8/14 MTX/CSA required at least 2 drugs. The 5-year overall survival rates were 52% and 52% ( P = 0.859), and the 5-year disease-free survival rates were 52% and 52% ( P = 0.862) for the MTX/CSA and PTCy/ATG groups, respectively. We conclude that PTCy in combination with ATG without immunosuppression of a calcineurin inhibitor can effectively control GvHD.
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	SAGE Publishing
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Intermittent compressive force regulates human periodontal ligament cell behavior via yes-associated protein

Nuttha Klincumhom / Chanchao Lorthongpanich / Kanjana Thumanu / Praphasri Septham / Wutthikiat Phomyu / Surapol Issaragrisil / Prasit Pavasant

Heliyon, Vol 8, Iss 10, Pp e10845- (2022)

2022

Abstract: Intermittent compressive force influences human periodontal ligament (PDL) cell behavior that facilitates periodontal tissue regeneration. In response to mechanical stimuli, Yes-associated protein (YAP) has been recognized as a mechanosensitive ... ...

Abstract	Intermittent compressive force influences human periodontal ligament (PDL) cell behavior that facilitates periodontal tissue regeneration. In response to mechanical stimuli, Yes-associated protein (YAP) has been recognized as a mechanosensitive transcriptional activator that regulates cell proliferation and cell fate decisions. This study aimed to investigate whether compressive forces influence cell proliferation and cell fate decisions of human PDL cells via YAP signaling. YAP expression was silenced by shRNA. The effect of YAP on cell proliferation, adipogenesis and osteogenesis of PDL cells under ICF loading were determined. Adipogenic differentiation bias upon ICF loading was confirmed by fourier-transform infrared spectroscopy (FTIR). The results revealed that ICF-induced YAP promotes osteogenesis, but it inhibits adipogenesis in PDL cells. Depletion of YAP results in PDL cells that are irresponsive to ICF and, therefore, the failure of the PDL cells to undergo osteogenic differentiation. This was shown by a significant reduction in calcium deposited in the CF-derived osteoblasts of the YAP-knockdown (YAP-KD) PDL cells. As to control treatment, reduction of YAP promoted adipogenesis, whereas ICF-induced YAP inhibited this mechanism. However, the adipocyte differentiation in YAP-KD cells was not affected upon ICF treatment as the YAP-KD cells still exhibited a better adipogenic differentiation that was unrelated to the ICF. This study demonstrated that, in response to ICF treatment, YAP could be a crucial mechanosensitive transcriptional activator for the regulation of PDL cell behavior through a mechanobiological process. Our results may provide the possibility of facilitating PDL tissue regeneration by manipulation of the Hippo-YAP signaling pathway.
Keywords	Cell fate decision ; FTIR ; Hippo signaling pathway ; Human periodontal ligament cells ; Intermittent compressive force ; Yes-associated protein ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
Subject code	570
Language	English
Publishing date	2022-10-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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

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

Stem Cell Research & Therapy, Vol 13, Iss 1, Pp 1-

2022 Volume 21

Abstract: Abstract Background Human erythropoiesis is a tightly regulated, multistep process encompassing the differentiation of hematopoietic stem cells (HSCs) toward mature erythrocytes. Cellular metabolism is an important regulator of cell fate determination ... ...

Abstract	Abstract Background Human erythropoiesis is a tightly regulated, multistep process encompassing the differentiation of hematopoietic stem cells (HSCs) toward mature erythrocytes. Cellular metabolism is an important regulator of cell fate determination during the differentiation of HSCs. However, how O-GlcNAcylation, a posttranslational modification of proteins that is an ideal metabolic sensor, contributes to the commitment of HSCs to the erythroid lineage and to the terminal erythroid differentiation has not been addressed. Methods Cellular O-GlcNAcylation was manipulated using small molecule inhibition or CRISPR/Cas9 manipulation of catalyzing enzyme O-GlcNAc transferase (OGT) and removing enzyme O-GlcNAcase (OGA) in two cell models of erythroid differentiation, starting from: (i) human umbilical cord blood-derived CD34+ hematopoietic stem/progenitor cells (HSPCs) to investigate the erythroid lineage specification and differentiation; and (ii) human-derived erythroblastic leukemia K562 cells to investigate the terminal differentiation. The functional and regulatory roles of O-GlcNAcylation in erythroid differentiation, maturation, and globin production were investigated, and downstream signaling was delineated. Results First, we observed that two-step inhibition of OGT and OGA, which were established from the observed dynamics of O-GlcNAc level along the course of differentiation, promotes HSPCs toward erythroid differentiation and enucleation, in agreement with an upregulation of a multitude of erythroid-associated genes. Further studies in the efficient K562 model of erythroid differentiation confirmed that OGA inhibition and subsequent hyper-O-GlcNAcylation enhance terminal erythroid differentiation and affect globin production. Mechanistically, we found that BCL11A is a key mediator of O-GlcNAc-driven erythroid differentiation and β- and α-globin production herein. Additionally, analysis of biochemical contents using synchrotron-based Fourier transform infrared (FTIR) spectroscopy showed unique metabolic ...
Keywords	O-GlcNAcylation ; Hematopoietic stem cells ; Erythroblasts ; Erythropoiesis ; Erythroid differentiation ; Erythroid maturation ; Medicine (General) ; R5-920 ; Biochemistry ; QD415-436
Subject code	571
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Correction

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

Stem Cell Research & Therapy, Vol 13, Iss 1, Pp 1-

Metabolic sensor O-GlcNAcylation regulates erythroid differentiation and globin production via BCL11A

2022 Volume 3

Keywords	Medicine (General) ; R5-920 ; Biochemistry ; QD415-436
Language	English
Publishing date	2022-08-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Hematopoietic stem cell transplantation for thalassemia

Surapol Issaragrisil

Cellular Therapy and Transplantation, Vol 2, Iss 7, p 2010;2:e.000070.

2010 Volume 01

Abstract: Hematopoietic stem cell transplantation is the only modality that offers the potential of cure for severe thalassemia, including homozygous β-thalassemia and severe Hb E/β-thalassemia. All children with class 1 or 2 disease should be transplanted if they ...

Abstract	Hematopoietic stem cell transplantation is the only modality that offers the potential of cure for severe thalassemia, including homozygous β-thalassemia and severe Hb E/β-thalassemia. All children with class 1 or 2 disease should be transplanted if they have HLA-identical siblings, and transplantation should be performed as early as possible. Sibling cord blood transplantation is recommended in children with class 1 or 2 of the disease if adequate numbers of cord blood cells from younger siblings are available.Bone marrow transplantation in class 3 children and adult patients with appropriate conditioning regimen gives results that are superior to those obtained with cord blood. However, we recommend that patients and their families should discuss in detail the risks and benefits, and transplantation should be performed in only motivated patients who have a clear understanding of the entire process. There is new hope that haploidentical transplantation will be successful, but further studies are required to confirm early results.
Keywords	thalassemia ; clinical risk factors ; hematopoietic stem cell transplantation ; indications ; benefits ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Oncology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	610
Language	English
Publishing date	2010-11-01T00:00:00Z
Publisher	Hamburg University Medical Center, St.Petersburg State Medical I.Pavlov University
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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