Microcarrier-Expanded Neural Progenitor Cells Can Survive, Differentiate, and Innervate Host Neurons Better When Transplanted as Aggregates
Neuronal progenitor cells (NPCs) derived from human embryonic stem cells (hESCs) are an excellent cell source for transplantation therapy due to their availability and ethical acceptability. However, the traditional method of expansion and differentiation of hESCs into NPCs in monolayer cultures req...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2016-07-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368915X690378 |
| _version_ | 1819204796052144128 |
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| author | Lifeng Qiu Yu Ming Lim Allen K. Chen Shaul Reuveny Steve K. W. Oh Eng King Tan Li Zeng |
| author_facet | Lifeng Qiu Yu Ming Lim Allen K. Chen Shaul Reuveny Steve K. W. Oh Eng King Tan Li Zeng |
| author_sort | Lifeng Qiu |
| collection | DOAJ |
| description | Neuronal progenitor cells (NPCs) derived from human embryonic stem cells (hESCs) are an excellent cell source for transplantation therapy due to their availability and ethical acceptability. However, the traditional method of expansion and differentiation of hESCs into NPCs in monolayer cultures requires a long time, and the cell yield is low. A microcarrier (MC) platform can improve the expansion of hESCs and increase the yield of NPCs. In this study, for the first time, we transplanted microcarrier-expanded hESC-derived NPCs into the striatum of adult NOD-SCID IL2Rgc null mice, either as single cells or as cell aggregates. The recipient mice were perfused, and the in vivo survival, differentiation, and targeted innervation of the transplanted cells were assessed by immunostaining. We found that both the transplanted single NPCs and aggregate NPCs were able to survive 1 month posttransplantation, as revealed by human-specific neural cell adhesion molecule (NCAM) and human nuclear antigen staining. Compared to the single cells, the transplanted cell aggregates showed better survival over a 3-month period. In addition, both the transplanted single NPCs and the aggregate NPCs were able to differentiate into DCX-positive immature neurons and Tuj1-positive neurons in vivo by 1 month posttransplantation. However, only the transplantation of aggregate NPCs was shown to result in mature neurons at 3 months posttransplantation. Furthermore, we found that the cell aggregates were able to send long axons to innervate their targets. Our study provides preclinical evidence that the use of MCs to expand and differentiate hESC-derived NPCs and transplantation of these cells as aggregates produce longer survival in vivo. |
| first_indexed | 2024-12-23T04:41:30Z |
| format | Article |
| id | doaj.art-f74534733cff4ee486fb440a397ccb63 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-23T04:41:30Z |
| publishDate | 2016-07-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-f74534733cff4ee486fb440a397ccb632022-12-21T17:59:47ZengSAGE PublishingCell Transplantation0963-68971555-38922016-07-012510.3727/096368915X690378Microcarrier-Expanded Neural Progenitor Cells Can Survive, Differentiate, and Innervate Host Neurons Better When Transplanted as AggregatesLifeng Qiu0Yu Ming Lim1Allen K. Chen2Shaul Reuveny3Steve K. W. Oh4Eng King Tan5Li Zeng6Neural Stem Cell Research Lab, Research Department, National Neuroscience Institute, SingaporeStem Cell Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research (A STAR), SingaporeStem Cell Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research (A STAR), SingaporeStem Cell Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research (A STAR), SingaporeStem Cell Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research (A STAR), SingaporeNeuroscience and Behavioral Disorders Program, DUKE-NUS Graduate Medical School, SingaporeNeuroscience and Behavioral Disorders Program, DUKE-NUS Graduate Medical School, SingaporeNeuronal progenitor cells (NPCs) derived from human embryonic stem cells (hESCs) are an excellent cell source for transplantation therapy due to their availability and ethical acceptability. However, the traditional method of expansion and differentiation of hESCs into NPCs in monolayer cultures requires a long time, and the cell yield is low. A microcarrier (MC) platform can improve the expansion of hESCs and increase the yield of NPCs. In this study, for the first time, we transplanted microcarrier-expanded hESC-derived NPCs into the striatum of adult NOD-SCID IL2Rgc null mice, either as single cells or as cell aggregates. The recipient mice were perfused, and the in vivo survival, differentiation, and targeted innervation of the transplanted cells were assessed by immunostaining. We found that both the transplanted single NPCs and aggregate NPCs were able to survive 1 month posttransplantation, as revealed by human-specific neural cell adhesion molecule (NCAM) and human nuclear antigen staining. Compared to the single cells, the transplanted cell aggregates showed better survival over a 3-month period. In addition, both the transplanted single NPCs and the aggregate NPCs were able to differentiate into DCX-positive immature neurons and Tuj1-positive neurons in vivo by 1 month posttransplantation. However, only the transplantation of aggregate NPCs was shown to result in mature neurons at 3 months posttransplantation. Furthermore, we found that the cell aggregates were able to send long axons to innervate their targets. Our study provides preclinical evidence that the use of MCs to expand and differentiate hESC-derived NPCs and transplantation of these cells as aggregates produce longer survival in vivo.https://doi.org/10.3727/096368915X690378 |
| spellingShingle | Lifeng Qiu Yu Ming Lim Allen K. Chen Shaul Reuveny Steve K. W. Oh Eng King Tan Li Zeng Microcarrier-Expanded Neural Progenitor Cells Can Survive, Differentiate, and Innervate Host Neurons Better When Transplanted as Aggregates Cell Transplantation |
| title | Microcarrier-Expanded Neural Progenitor Cells Can Survive, Differentiate, and Innervate Host Neurons Better When Transplanted as Aggregates |
| title_full | Microcarrier-Expanded Neural Progenitor Cells Can Survive, Differentiate, and Innervate Host Neurons Better When Transplanted as Aggregates |
| title_fullStr | Microcarrier-Expanded Neural Progenitor Cells Can Survive, Differentiate, and Innervate Host Neurons Better When Transplanted as Aggregates |
| title_full_unstemmed | Microcarrier-Expanded Neural Progenitor Cells Can Survive, Differentiate, and Innervate Host Neurons Better When Transplanted as Aggregates |
| title_short | Microcarrier-Expanded Neural Progenitor Cells Can Survive, Differentiate, and Innervate Host Neurons Better When Transplanted as Aggregates |
| title_sort | microcarrier expanded neural progenitor cells can survive differentiate and innervate host neurons better when transplanted as aggregates |
| url | https://doi.org/10.3727/096368915X690378 |
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