Expandable Sendai-Virus-Reprogrammed Human iPSC-Neuronal Precursors: In Vivo Post-Grafting Safety Characterization in Rats and Adult Pig

One of the challenges in clinical translation of cell-replacement therapies is the definition of optimal cell generation and storage/recovery protocols which would permit a rapid preparation of cell-treatment products for patient administration. Besides, the availability of injection devices that ar...

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Published inCell transplantation Vol. 32; p. 9636897221107009
Main Authors Kobayashi, Yoshiomi, Shigyo, Michiko, Platoshyn, Oleksandr, Marsala, Silvia, Kato, Tomohisa, Takamura, Naoki, Yoshida, Kenji, Kishino, Akiyoshi, Bravo-Hernandez, Mariana, Juhas, Stefan, Juhasova, Jana, Studenovska, Hana, Proks, Vladimir, Driscoll, Shawn P., Glenn, Thomas D., Pfaff, Samuel L., Ciacci, Joseph D., Marsala, Martin
Format Journal Article
LanguageEnglish
Published Los Angeles, CA SAGE Publications 01.01.2023
Sage Publications Ltd
Subjects
Adult
Animals
Brain
Cell culture
Cell differentiation
Cell Differentiation - physiology
Cellular Reprogramming - genetics
Cellular Reprogramming - physiology
Genetic Vectors - genetics
Graft Survival - physiology
Humans
Immunodeficiency
Induced Pluripotent Stem Cells - physiology
Induced Pluripotent Stem Cells - transplantation
Injection
Injections, Spinal - adverse effects
Injections, Spinal - instrumentation
Injections, Spinal - methods
Neural stem cells
Neural Stem Cells - physiology
Neural Stem Cells - transplantation
Original
Pluripotency
Rats
Sendai virus
Specimen Handling - methods
Spinal Cord
Stem Cell Transplantation - adverse effects
Stem Cell Transplantation - instrumentation
Stem Cell Transplantation - methods
Swine
Tissue and Organ Harvesting - methods
Treatment Outcome
human induced pluripotent stem cells (hiPSCs)
neural precursor cells (NPCs)
spinal cord
human injection device
immunosuppressed adult pig
cryopreservation
Online AccessGet full text
ISSN0963-6897
1555-3892
1555-3892
DOI10.1177/09636897221107009

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Abstract One of the challenges in clinical translation of cell-replacement therapies is the definition of optimal cell generation and storage/recovery protocols which would permit a rapid preparation of cell-treatment products for patient administration. Besides, the availability of injection devices that are simple to use is critical for potential future dissemination of any spinally targeted cell-replacement therapy into general medical practice. Here, we compared the engraftment properties of established human-induced pluripotent stem cells (hiPSCs)-derived neural precursor cell (NPCs) line once cells were harvested fresh from the cell culture or previously frozen and then grafted into striata or spinal cord of the immunodeficient rat. A newly developed human spinal injection device equipped with a spinal cord pulsation-cancelation magnetic needle was also tested for its safety in an adult immunosuppressed pig. Previously frozen NPCs showed similar post-grafting survival and differentiation profile as was seen for freshly harvested cells. Testing of human injection device showed acceptable safety with no detectable surgical procedure or spinal NPCs injection-related side effects.
AbstractList One of the challenges in clinical translation of cell-replacement therapies is the definition of optimal cell generation and storage/recovery protocols which would permit a rapid preparation of cell-treatment products for patient administration. Besides, the availability of injection devices that are simple to use is critical for potential future dissemination of any spinally targeted cell-replacement therapy into general medical practice. Here, we compared the engraftment properties of established human-induced pluripotent stem cells (hiPSCs)-derived neural precursor cell (NPCs) line once cells were harvested fresh from the cell culture or previously frozen and then grafted into striata or spinal cord of the immunodeficient rat. A newly developed human spinal injection device equipped with a spinal cord pulsation-cancelation magnetic needle was also tested for its safety in an adult immunosuppressed pig. Previously frozen NPCs showed similar post-grafting survival and differentiation profile as was seen for freshly harvested cells. Testing of human injection device showed acceptable safety with no detectable surgical procedure or spinal NPCs injection-related side effects.One of the challenges in clinical translation of cell-replacement therapies is the definition of optimal cell generation and storage/recovery protocols which would permit a rapid preparation of cell-treatment products for patient administration. Besides, the availability of injection devices that are simple to use is critical for potential future dissemination of any spinally targeted cell-replacement therapy into general medical practice. Here, we compared the engraftment properties of established human-induced pluripotent stem cells (hiPSCs)-derived neural precursor cell (NPCs) line once cells were harvested fresh from the cell culture or previously frozen and then grafted into striata or spinal cord of the immunodeficient rat. A newly developed human spinal injection device equipped with a spinal cord pulsation-cancelation magnetic needle was also tested for its safety in an adult immunosuppressed pig. Previously frozen NPCs showed similar post-grafting survival and differentiation profile as was seen for freshly harvested cells. Testing of human injection device showed acceptable safety with no detectable surgical procedure or spinal NPCs injection-related side effects.
One of the challenges in clinical translation of cell-replacement therapies is the definition of optimal cell generation and storage/recovery protocols which would permit a rapid preparation of cell-treatment products for patient administration. Besides, the availability of injection devices that are simple to use is critical for potential future dissemination of any spinally targeted cell-replacement therapy into general medical practice. Here, we compared the engraftment properties of established human-induced pluripotent stem cells (hiPSCs)-derived neural precursor cell (NPCs) line once cells were harvested fresh from the cell culture or previously frozen and then grafted into striata or spinal cord of the immunodeficient rat. A newly developed human spinal injection device equipped with a spinal cord pulsation-cancelation magnetic needle was also tested for its safety in an adult immunosuppressed pig. Previously frozen NPCs showed similar post-grafting survival and differentiation profile as was seen for freshly harvested cells. Testing of human injection device showed acceptable safety with no detectable surgical procedure or spinal NPCs injection-related side effects.
Author Glenn, Thomas D.
Proks, Vladimir
Platoshyn, Oleksandr
Kato, Tomohisa
Bravo-Hernandez, Mariana
Juhas, Stefan
Yoshida, Kenji
Shigyo, Michiko
Takamura, Naoki
Pfaff, Samuel L.
Juhasova, Jana
Kobayashi, Yoshiomi
Kishino, Akiyoshi
Ciacci, Joseph D.
Marsala, Silvia
Studenovska, Hana
Driscoll, Shawn P.
Marsala, Martin
AuthorAffiliation 2 Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan
1 Department of Anesthesiology, School of Medicine, University of California, San Diego, San Diego, CA, USA
7 Gene Expression Laboratory, Howard Hughes Medical Institute and Salk Institute for Biological Studies, La Jolla, CA, USA
8 Department of Neurosurgery, School of Medicine, University of California, San Diego, San Diego, CA, USA
3 Regenerative & Cellular Medicine Kobe Center, Sumitomo Dainippon Pharma Co., Ltd., Kobe, Japan
4 Division of Stem Cell Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Uchinada, Japan
5 Institute of Animal Physiology and Genetics, AS CR v.v.i., Liběchov, Czech Republic
6 Department of Biomaterials and Bioanalogous System, Institute of Macromolecular Chemistry, Czech Academy of Sciences, Prague, Czech Republic
AuthorAffiliation_xml – name: 5 Institute of Animal Physiology and Genetics, AS CR v.v.i., Liběchov, Czech Republic
– name: 1 Department of Anesthesiology, School of Medicine, University of California, San Diego, San Diego, CA, USA
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– name: 6 Department of Biomaterials and Bioanalogous System, Institute of Macromolecular Chemistry, Czech Academy of Sciences, Prague, Czech Republic
– name: 7 Gene Expression Laboratory, Howard Hughes Medical Institute and Salk Institute for Biological Studies, La Jolla, CA, USA
– name: 2 Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan
– name: 8 Department of Neurosurgery, School of Medicine, University of California, San Diego, San Diego, CA, USA
– name: 3 Regenerative & Cellular Medicine Kobe Center, Sumitomo Dainippon Pharma Co., Ltd., Kobe, Japan
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Keywords human induced pluripotent stem cells (hiPSCs)
neural precursor cells (NPCs)
spinal cord
human injection device
immunosuppressed adult pig
cryopreservation
Language English
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Yoshiomi Kobayashi is also affilated to The National Medical Center for Spine and Spinal Cord disease, Murayama Medical Center, Gakuen, Musashimurayama city, Tokyo, Japan
Co-first author
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Snippet One of the challenges in clinical translation of cell-replacement therapies is the definition of optimal cell generation and storage/recovery protocols which...
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StartPage 9636897221107009
SubjectTerms Adult
Animals
Brain
Cell culture
Cell differentiation
Cell Differentiation - physiology
Cellular Reprogramming - genetics
Cellular Reprogramming - physiology
Genetic Vectors - genetics
Graft Survival - physiology
Humans
Immunodeficiency
Induced Pluripotent Stem Cells - physiology
Induced Pluripotent Stem Cells - transplantation
Injection
Injections, Spinal - adverse effects
Injections, Spinal - instrumentation
Injections, Spinal - methods
Neural stem cells
Neural Stem Cells - physiology
Neural Stem Cells - transplantation
Original
Pluripotency
Rats
Sendai virus
Specimen Handling - methods
Spinal Cord
Stem Cell Transplantation - adverse effects
Stem Cell Transplantation - instrumentation
Stem Cell Transplantation - methods
Swine
Tissue and Organ Harvesting - methods
Treatment Outcome
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Title Expandable Sendai-Virus-Reprogrammed Human iPSC-Neuronal Precursors: In Vivo Post-Grafting Safety Characterization in Rats and Adult Pig
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