Natural Killer Cells Prevent the Formation of Teratomas Derived From Human Induced Pluripotent Stem Cells

Benabdallah, Basma; Désaulniers-Langevin, Cynthia; Colas, Chloé; Li, Yuanyi; Rousseau, Guy; Guimond, Jean; Haddad, Élie; Beauséjour, Christian

doi:10.3389/fimmu.2019.02580

Cited by 14 publications

(16 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, because most of hPSC transplantation studies are performed in immune-deficient animals or in presence of immune-suppressive drugs, the real risk of tumor formation in immune-competent hosts is mostly unknown. Recently, using multiple models of humanized mice it has been suggested that autologous hPSC-derived therapies are unlikely to form teratomas in the presence of natural killer (NK) cells [ 137 ].…”

Section: Current Challengesmentioning

confidence: 99%

Human Pluripotent Stem Cells-Based Therapies for Neurodegenerative Diseases: Current Status and Challenges

Ford

Pearlman

Ruan

et al. 2020

Cells

View full text Add to dashboard Cite

Neurodegenerative diseases are characterized by irreversible cell damage, loss of neuronal cells and limited regeneration potential of the adult nervous system. Pluripotent stem cells are capable of differentiating into the multitude of cell types that compose the central and peripheral nervous systems and so have become the major focus of cell replacement therapies for the treatment of neurological disorders. Human embryonic stem cell (hESC) and human induced pluripotent stem cell (hiPSC)-derived cells have both been extensively studied as cell therapies in a wide range of neurodegenerative disease models in rodents and non-human primates, including Parkinson’s disease, stroke, epilepsy, spinal cord injury, Alzheimer’s disease, multiple sclerosis and pain. In this review, we discuss the latest progress made with stem cell therapies targeting these pathologies. We also evaluate the challenges in clinical application of human pluripotent stem cell (hPSC)-based therapies including risk of oncogenesis and tumor formation, immune rejection and difficulty in regeneration of the heterogeneous cell types composing the central nervous system.

show abstract

Section: Current Challengesmentioning

confidence: 99%

Human Pluripotent Stem Cells-Based Therapies for Neurodegenerative Diseases: Current Status and Challenges

Ford

Pearlman

Ruan

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…In addition, none of hiPSC‐MPCs or their derived myotubes were able to induce NK cell‐degranulation and/or specific cytotoxicity (Figure 3D‐G). This could be explained by the fact that hiPSC‐MPCs, in opposition to hiPSC, express high levels of HLA‐I as we have shown before 13 …”

Section: Resultsmentioning

confidence: 58%

“…The fact that MPCs were not rejected by NK cells in Hu‐AT mice cannot be explain by an insufficient number of NK cells injected. Indeed, we recently showed the injection of a similar number of NK cells was sufficient to prevent the growth of iPSC‐derived teratomas in the same model 13 …”

Section: Discussionmentioning

confidence: 96%

“…MPCs were not rejected by NK cells in Hu-AT mice cannot be explain by an insufficient number of NK cells injected. Indeed, we recently showed the injection of a similar number of NK cells was sufficient to prevent the growth of iPSC-derived teratomas in the same model 13. Moreover, our observation in Hu-BLT mice that MPCs attract autologous CD4 and CD8 T cells at a level similar to that of myoblastsderived from a muscle biopsy, yet without compromising engraftment, was surprising.…”

mentioning

confidence: 86%

“…This could be explained by the fact that hiPSC-MPCs, in opposition to hiPSC, express high levels of HLA-I as we have shown before. 13…”

Section: To Determine If the Low Level Infiltration Of Autologous T Cmentioning

confidence: 99%

See 2 more Smart Citations

Myogenic progenitor cells derived from human induced pluripotent stem cell are immune-tolerated in humanized mice

Benabdallah

Désaulniers-Langevin

Goyer

et al. 2020

Stem Cells Translational Medicine

Self Cite

View full text Add to dashboard Cite

It is still unclear if immune responses will compromise the large‐scale utilization of human induced pluripotent stem cells (hiPSCs)‐derived cell therapies. To answer this question, we used humanized mouse models generated by the adoptive transfer of peripheral blood mononuclear cells or the cotransplantation of hematopoietic stem cells and human thymic tissue. Using these mice, we evaluated the engraftment in skeletal muscle of myoblasts derived either directly from a muscle biopsy or differentiated from hiPSCs or fibroblasts. Our results showed that while allogeneic grafts were mostly rejected and highly infiltrated with human T cells, engraftment of autologous cells was tolerated. We also observed that hiPSC‐derived myogenic progenitor cells (MPCs) are not targeted by autologous T cells and natural killer cells in vitro. These findings suggest that the reprogramming and differentiation procedures we used are not immunogenic and that hiPSC‐derived MPCs will be tolerated in the presence of a competent human immune system.

show abstract

CAR-NK Cells from Engineered Pluripotent Stem Cells: Off-the-shelf Therapeutics for all Patients

Lu¹,

Feng²

2021

Stem Cells Translational Medicine

View full text Add to dashboard Cite

Clinical success of adoptive cell therapy with chimeric antigen receptor (CAR) T cells for treating hematological malignancies has revolutionized the field of cellular immunotherapy. However, due to the nature of utilizing autologous T cells, affordability and availability are major hurdles, in addition to scientific challenges relating to CAR-T therapy optimization. Natural killer (NK) cell is a specialized immune effector cell type that recognizes and kills targets without human leukocyte antigen (HLA) restriction and prior sensitization. CAR-NK cells do not cause graft vs host disease and can be obtained from unrelated donors as well as pluripotent stem cells (PSC), representing an ideal off-the-shelf therapeutics readily available for patients. Furthermore, unlike cytotoxic T cells, NK cells specifically target and eliminate cancer stem cells, which are the cells causing relapse and metastasis. PSCs can be genetically manipulated and engineered with CARs at the pluripotent stage, which allows the establishment of permanent, stable, and clonal PSC-CAR lines for the manufacture of unlimited homogenous CAR-NK cells. Multiple master PSC-CAR cell banks targeting a variety of antigens for cancer, viral infection, and autoimmune diseases provide inexhaustible cell sources for all patients. Development of a next-generation 3D bioreactor platform for PSC expansion and NK cell production overcomes major barriers related to cost and scalability for CAR-NK product.

show abstract

Natural Killer Cells Prevent the Formation of Teratomas Derived From Human Induced Pluripotent Stem Cells

Cited by 14 publications

References 17 publications

Human Pluripotent Stem Cells-Based Therapies for Neurodegenerative Diseases: Current Status and Challenges

Human Pluripotent Stem Cells-Based Therapies for Neurodegenerative Diseases: Current Status and Challenges

Myogenic progenitor cells derived from human induced pluripotent stem cell are immune-tolerated in humanized mice

CAR-NK Cells from Engineered Pluripotent Stem Cells: Off-the-shelf Therapeutics for all Patients

Contact Info

Product

Resources

About