Induced Pluripotent Stem Cells (iPSCs) Provide a Potentially Unlimited T Cell Source for CAR-T Cell Development and Off-the-Shelf Products

2021 ◽  
Author(s):  
Muhammad Sadeqi Nezhad ◽  
Meghdad Abdollahpour-Alitappeh ◽  
Behzad Rezaei ◽  
Mahboubeh Yazdanifar ◽  
Alexander Marcus Seifalian
Keyword(s):  
Stem Cells ◽  
T Cell ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
T Cell Development ◽  
Cell Development ◽  
Car T Cell ◽  
Car T ◽  
Cell Source ◽  
Induced Pluripotent

scholarly journals Induced Pluripotent Stem Cells Provide an Unlimited T-cell Source for CAR-T cell Development and A Potential Source for Off-the-shelf Products

2021 ◽  
Author(s):  
Muhammad Sadeqi Nezhad
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Pluripotent Stem Cells ◽  
T Cell Development ◽  
Cell Development ◽  
Car T Cell ◽  
Car T ◽  
Cell Source

CAR-T cell therapy has been increasingly conducted for cancer patients in clinical settings. Progress in this therapeutic approach is hampered by the lack of a solid manufacturing process, T lymphocytes, and tumor-specific antigens. T-cell source used in CAR-T cell therapy is predominantly derived from the patient’s own T lymphocytes, which makes this approach impracticable to patients with progressive diseases and T leukemia. Autologous CAR-T cell generation is time-consuming due to lack of readily available T lymphocytes and is not applicable for third-party patients. Pluripotent stem cells, such as human induced pluripotent stem cells (hiPSCs), could provide an unlimited T-cell source for CAR-T cell development. iPSC-derived T cells would be a promising infinite T-cell source and are phenotypically defined, expandable and functional as physiological T cells. iPSC-derived T cells provide a feasible T-cell source for the development of off-the-shelf T cells and CAR-T cells. The combination of iPSC and CAR technologies provides an extraordinary opportunity to oncology and greatly facilitates cell-based therapy for cancer patients. T-iPSCs in combination with CAR is in early stage of development and the pre-clinical and clinical studies concerning the combination of these novel technologies are not sufficient. This article critically reviews the progress in iPSC-derived T cell development, and it considers the opportunity to convert iPSC-derived T cells into off-the-shelf T cells for universal CAR-T cell treatment.

scholarly journals Induced Pluripotent Stem Cells Provide an Unlimited T-cell Source for CAR-T cell Development and A Potential Source for Off-the-shelf Products

2021 ◽  
Author(s):  
Muhammad Sadeqi Nezhad
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Pluripotent Stem Cells ◽  
T Cell Development ◽  
Cell Development ◽  
Car T Cell ◽  
Car T ◽  
Cell Source

CAR-T cell therapy has been increasingly conducted for cancer patients in clinical settings. Progress in this therapeutic approach is hampered by the lack of a solid manufacturing process, T lymphocytes, and tumor-specific antigens. T-cell source used in CAR-T cell therapy is predominantly derived from the patient’s own T lymphocytes, which makes this approach impracticable to patients with progressive diseases and T leukemia. Autologous CAR-T cell generation is time-consuming due to lack of readily available T lymphocytes and is not applicable for third-party patients. Pluripotent stem cells, such as human induced pluripotent stem cells (hiPSCs), could provide an unlimited T-cell source for CAR-T cell development. iPSC-derived T cells would be a promising infinite T-cell source and are phenotypically defined, expandable and functional as physiological T cells. iPSC-derived T cells provide a feasible T-cell source for the development of off-the-shelf T cells and CAR-T cells. The combination of iPSC and CAR-Technologies provides an extraordinary opportunity to oncology and greatly facilitates cell-based therapy for cancer patients. T-iPSCs in combination with CAR is in early stage of development and the pre-clinical and clinical studies concerning the combination of these novel technologies are not sufficient. This article critically reviews the progress in iPSC-derived T cell development and provides a roadmap for development of CAR iPSC-derived T cells and off-the-shelf T-iPSCs. Keywords: CAR-T cell; iPSC; T cell; iPSC-derived T cell; tumor cell; therapeutic; off-the-shelf

scholarly journals Induced Pluripotent Stem Cells Provide an Unlimited T-cell Source for CAR-T cell Development and A Potential Source for Off-the-shelf Products

2021 ◽  
Author(s):  
Muhammad Sadeqi Nezhad
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Pluripotent Stem Cells ◽  
T Cell Development ◽  
Cell Development ◽  
Car T Cell ◽  
Car T ◽  
Cell Source

CAR-T cell therapy has been increasingly conducted for cancer patients in clinical settings. Progress in this therapeutic approach is hampered by the lack of a solid manufacturing process, T lymphocytes, and tumor-specific antigens. T-cell source used in CAR-T cell therapy is predominantly derived from the patient’s own T lymphocytes, which makes this approach impracticable to patients with progressive diseases and T leukemia. Autologous CAR-T cell generation is time-consuming due to lack of readily available T lymphocytes and is not applicable for third-party patients. Pluripotent stem cells, such as human induced pluripotent stem cells (hiPSCs), could provide an unlimited T-cell source for CAR-T cell development. iPSC-derived T cells would be a promising infinite T-cell source and are phenotypically defined, expandable and functional as physiological T cells. iPSC-derived T cells provide a feasible T-cell source for the development of off-the-shelf T cells and CAR-T cells. The combination of iPSC and CAR-Technologies provides an extraordinary opportunity to oncology and greatly facilitates cell-based therapy for cancer patients. T-iPSCs in combination with CAR is in early stage of development and the pre-clinical and clinical studies concerning the combination of these novel technologies are not sufficient. This article critically reviews the progress in iPSC-derived T cell development and provides a roadmap for development of CAR iPSC-derived T cells and off-the-shelf T-iPSCs. Keywords: CAR-T cell; iPSC; T cell; iPSC-derived T cell; tumor cell; therapeutic; off-the-shelf

Abstract 219: Induced Pluripotent Stem Cells as a Potential Cell Source for Tissue Engineered Heart Valves

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Aline L Yonezawa ◽  
Monalisa Singh ◽  
David Safranski ◽  
Kenneth M Dupont ◽  
Chunhui Xu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Heart Valves ◽  
3D Culture ◽  
Polyethylene Glycol Diacrylate ◽  
Glycol Diacrylate ◽  
Cell Source ◽  
Induced Pluripotent ◽  
Tissue Engineered Heart Valves

Despite recent advances in tissue engineered heart valves (TEHV), one of the major challenges is finding a suitable cell source for seeding TEHV scaffolds. Native heart valves are durable because valve interstitial cells (VICs) maintain tissue homeostasis by synthesizing and remodeling the extracellular matrix. In this study, we demonstrate that induced pluripotent stem cells (iPSCs) can be derived into induced mesenchymal stem cells (iMSCs) using our feeder-free protocol and then further differentiated into VICs using a 3D cell culture environment. The differentiation efficiency was quantified using flow cytometry, immunohistochemistry staining, RT-PCR, and trilineage differentiation. In addition, iMSCs were encapsulated in polyethylene (glycol) diacrylate (PEGDA) hydrogels of varying stiffness, grafted with adhesion peptide (RGDS), to promote cell proliferation, remodeling, and further differentiation into VIC-like cells. VICs phenotype was characterized by the expression of αSMA, vimentin, F-actin, and the ECM production after 7, 14, and 21 days. The results demonstrated that using our feeder-free differentiation protocol, iMSCs were differentiated from iPSCs. Our iMSCs had a 99.9% and 99.4% positive expression for MSC markers CD90 and CD44, respectively. As expected, there was 0.019% expression of CD45, which is a hematopoietic marker. In addition, iMSCs differentiated into adipogenic, chondrogenic, and osteogenic. When MSC derived cells were encapsulated in PEGDA hydrogels that mimic the leaflet modulus, we observed expression of αSMA and F-actin after 7 days. Thus, the results from this study suggest that iPSCs can be a suitable cell source for TEHV by using a feeder-free differentiation approach and 3D culture.

scholarly journals In Vitro T-Cell Generation From Adult, Embryonic, and Induced Pluripotent Stem Cells: Many Roads to One Destination

Stem Cells ◽  
2015 ◽  
Vol 33 (11) ◽  
pp. 3174-3180 ◽  
Author(s):  
Michelle J. Smith ◽  
Beau R. Webber ◽  
Mahmood Mohtashami ◽  
Heather E. Stefanski ◽  
Juan Carlos Zún˜iga-Pflücker ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cell ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cell Generation ◽  
Induced Pluripotent
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