Grafted human-induced pluripotent stem cells-derived oligodendrocyte progenitor cells combined with human umbilical vein endothelial cells contribute to functional recovery following spinal cord injury

Qian Li; Sumei Liu; Tianqi Zheng; Mo Li; Boling Qi; Liping Zhou; Bochao Liu; Dan Ma; Chao Zhao; Zhiguo Chen

doi:10.1186/s13287-024-03651-1

Grafted human-induced pluripotent stem cells-derived oligodendrocyte progenitor cells combined with human umbilical vein endothelial cells contribute to functional recovery following spinal cord injury

Qian Li, Sumei Liu, Tianqi Zheng, Mo Li, Boling Qi, Liping Zhou, Bochao Liu, Dan Ma, Chao Zhao, Zhiguo Chen^*

^*Corresponding author for this work

Beijing Institute for Brain Disorders, Center of Parkinson’s Disease, Beijing, 100069, China, GRID: grid.24696.3f, ISNI: 0000 0004 0369 153X
University of Cambridge, Department of Clinical Neurosciences, Wellcome Trust-Medical Research Council Stem Cell Institute, Cambridge, UK, ROR: https://ror.org/013meh722, GRID: grid.5335.0, ISNI: 0000 0001 2188 5934

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Abstract

Background: Spinal cord injury (SCI) is a devastating disease that causes extensive damage to oligodendrocytes and neurons leading to demyelination and axonal degeneration. In this study, we co-transplanted cell grafts containing oligodendrocyte progenitor cells (OPCs) derived from human-induced pluripotent stem cells (iPSCs) combined with human umbilical vein endothelial cells (HUVECs), which were reported to promote OPCs survival and migration, into rat contusion models to promote functional recovery after SCI. Methods: OPCs were derived from iPSCs and identified by immunofluorescence at different time points. Functional assays in vitro were performed to evaluate the effect of HUVECs on the proliferation, migration, and survival of OPCs by co-culture and migration assay, as well as on the neuronal axonal growth. A combination of OPCs and HUVECs was transplanted into the rat contusive model. Upon 8 weeks, immunofluorescence staining was performed to test the safety of transplanted cells and to observe the neuronal repairment, myelination, and neural circuit reconstruction at the injured area; also, the functional recovery was assessed by Basso, Beattie, and Bresnahan open-field scale, Ladder climb, SEP, and MEP. Furthermore, the effect of HUVECs on grafts was also determined in vivo. Results: Data showed that HUVECs promote the proliferation, migration, and survival of OPCs both in vitro and in vivo. Furthermore, 8 weeks upon engraftment, the rats with OPCs and HUVECs co-transplantation noticeably facilitated remyelination, enhanced functional connection between the grafts and the host and promoted functional recovery. In addition, compared with the OPCs-alone transplantation, the co-transplantation generated more sensory neurons at the lesion border and significantly improved the sensory functional recovery. Conclusions: Our study demonstrates that transplantation of OPCs combined with HUVECs significantly enhances both motor and sensory functional recovery after SCI. No significance was observed between OPCs combined with HUVECs group and OPCs-alone group in motor function recovery, while the sensory function recovery was significantly promoted in OPCs combined with HUVECs groups compared with the other two groups. These findings provide novel insights into the field of SCI research.

Original language	English
Article number	35
Number of pages	20
Journal	Stem Cell Research & Therapy
Volume	15
Issue number	1
Early online date	7 Feb 2024
DOIs	https://doi.org/10.1186/s13287-024-03651-1
Publication status	Published - 7 Feb 2024

Bibliographical note

Copyright © The Author(s), 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (https://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Funding

This work was supported by Stem Cell and Translation National Key Project (2016YFA0101403), National Natural Science Foundation of China (82171250 and 81973351), Beijing Municipal Natural Science Foundation (5142005), Beijing Talents Foundation (2017000021223TD03), Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five–year Plan (CIT and TCD20180333), Beijing Municipal Health Commission Fund (PXM2020_026283_000005), Beijing One Hundred, Thousand, and Ten Thousand Talents Fund (2018A03), Royal Society-Newton Advanced Fellowship (NA150482), and National Science Foundation for Young Scientists of China (31900740). The funding body played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

Funders	Funder number
Royal Society-Newton	NA150482
Stem Cell and Translation National Key Project	2016YFA0101403
Ten Thousand Talents Fund	2018A03
Beijing Municipal Excellent Talents Foundation	2017000021223TD03
National Natural Science Foundation of China	31900740, 81973351, 82171250
Beijing Municipal Health Commission	PXM2020_026283_000005
Beijing Municipal Natural Science Foundation	5142005
Changshu Institute of Technology	TCD20180333
Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan

Keywords

Spinal cord injury
Induced pluripotent stem cells
HUVECs
Oligodendrocyte progenitor cells
Human Umbilical Vein Endothelial Cells
Spinal Cord Injuries/pathology
Humans
Induced Pluripotent Stem Cells/transplantation
Rats
Recovery of Function
Spinal Cord/pathology
Oligodendrocyte Precursor Cells/pathology
Animals
Cell Differentiation/physiology
Oligodendroglia

Access to Document

10.1186/s13287-024-03651-1

Q Li et al_pluripotent stem cells-derived oligodendrocyte progenitor cells combined with human umbilical vein endothelial cells_recovery following spinal injury
Copyright © The Author(s), 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (https://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Final published version, 7.13 MBLicence: CC BY 4.0

Cite this

Li, Q., Liu, S., Zheng, T., Li, M., Qi, B., Zhou, L., Liu, B., Ma, D., Zhao, C., & Chen, Z. (2024). Grafted human-induced pluripotent stem cells-derived oligodendrocyte progenitor cells combined with human umbilical vein endothelial cells contribute to functional recovery following spinal cord injury. Stem Cell Research & Therapy, 15(1), Article 35. https://doi.org/10.1186/s13287-024-03651-1

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abstract = "Background: Spinal cord injury (SCI) is a devastating disease that causes extensive damage to oligodendrocytes and neurons leading to demyelination and axonal degeneration. In this study, we co-transplanted cell grafts containing oligodendrocyte progenitor cells (OPCs) derived from human-induced pluripotent stem cells (iPSCs) combined with human umbilical vein endothelial cells (HUVECs), which were reported to promote OPCs survival and migration, into rat contusion models to promote functional recovery after SCI. Methods: OPCs were derived from iPSCs and identified by immunofluorescence at different time points. Functional assays in vitro were performed to evaluate the effect of HUVECs on the proliferation, migration, and survival of OPCs by co-culture and migration assay, as well as on the neuronal axonal growth. A combination of OPCs and HUVECs was transplanted into the rat contusive model. Upon 8 weeks, immunofluorescence staining was performed to test the safety of transplanted cells and to observe the neuronal repairment, myelination, and neural circuit reconstruction at the injured area; also, the functional recovery was assessed by Basso, Beattie, and Bresnahan open-field scale, Ladder climb, SEP, and MEP. Furthermore, the effect of HUVECs on grafts was also determined in vivo. Results: Data showed that HUVECs promote the proliferation, migration, and survival of OPCs both in vitro and in vivo. Furthermore, 8 weeks upon engraftment, the rats with OPCs and HUVECs co-transplantation noticeably facilitated remyelination, enhanced functional connection between the grafts and the host and promoted functional recovery. In addition, compared with the OPCs-alone transplantation, the co-transplantation generated more sensory neurons at the lesion border and significantly improved the sensory functional recovery. Conclusions: Our study demonstrates that transplantation of OPCs combined with HUVECs significantly enhances both motor and sensory functional recovery after SCI. No significance was observed between OPCs combined with HUVECs group and OPCs-alone group in motor function recovery, while the sensory function recovery was significantly promoted in OPCs combined with HUVECs groups compared with the other two groups. These findings provide novel insights into the field of SCI research.",

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author = "Qian Li and Sumei Liu and Tianqi Zheng and Mo Li and Boling Qi and Liping Zhou and Bochao Liu and Dan Ma and Chao Zhao and Zhiguo Chen",

note = "Copyright {\textcopyright} The Author(s), 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (https://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.",

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Li, Q, Liu, S, Zheng, T, Li, M, Qi, B, Zhou, L, Liu, B, Ma, D, Zhao, C & Chen, Z 2024, 'Grafted human-induced pluripotent stem cells-derived oligodendrocyte progenitor cells combined with human umbilical vein endothelial cells contribute to functional recovery following spinal cord injury', Stem Cell Research & Therapy, vol. 15, no. 1, 35. https://doi.org/10.1186/s13287-024-03651-1

Grafted human-induced pluripotent stem cells-derived oligodendrocyte progenitor cells combined with human umbilical vein endothelial cells contribute to functional recovery following spinal cord injury. / Li, Qian; Liu, Sumei; Zheng, Tianqi et al.
In: Stem Cell Research & Therapy, Vol. 15, No. 1, 35, 07.02.2024.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Grafted human-induced pluripotent stem cells-derived oligodendrocyte progenitor cells combined with human umbilical vein endothelial cells contribute to functional recovery following spinal cord injury

AU - Li, Qian

AU - Liu, Sumei

AU - Zheng, Tianqi

AU - Li, Mo

AU - Qi, Boling

AU - Zhou, Liping

AU - Liu, Bochao

AU - Ma, Dan

AU - Zhao, Chao

AU - Chen, Zhiguo

N1 - Copyright © The Author(s), 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (https://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

PY - 2024/2/7

Y1 - 2024/2/7

N2 - Background: Spinal cord injury (SCI) is a devastating disease that causes extensive damage to oligodendrocytes and neurons leading to demyelination and axonal degeneration. In this study, we co-transplanted cell grafts containing oligodendrocyte progenitor cells (OPCs) derived from human-induced pluripotent stem cells (iPSCs) combined with human umbilical vein endothelial cells (HUVECs), which were reported to promote OPCs survival and migration, into rat contusion models to promote functional recovery after SCI. Methods: OPCs were derived from iPSCs and identified by immunofluorescence at different time points. Functional assays in vitro were performed to evaluate the effect of HUVECs on the proliferation, migration, and survival of OPCs by co-culture and migration assay, as well as on the neuronal axonal growth. A combination of OPCs and HUVECs was transplanted into the rat contusive model. Upon 8 weeks, immunofluorescence staining was performed to test the safety of transplanted cells and to observe the neuronal repairment, myelination, and neural circuit reconstruction at the injured area; also, the functional recovery was assessed by Basso, Beattie, and Bresnahan open-field scale, Ladder climb, SEP, and MEP. Furthermore, the effect of HUVECs on grafts was also determined in vivo. Results: Data showed that HUVECs promote the proliferation, migration, and survival of OPCs both in vitro and in vivo. Furthermore, 8 weeks upon engraftment, the rats with OPCs and HUVECs co-transplantation noticeably facilitated remyelination, enhanced functional connection between the grafts and the host and promoted functional recovery. In addition, compared with the OPCs-alone transplantation, the co-transplantation generated more sensory neurons at the lesion border and significantly improved the sensory functional recovery. Conclusions: Our study demonstrates that transplantation of OPCs combined with HUVECs significantly enhances both motor and sensory functional recovery after SCI. No significance was observed between OPCs combined with HUVECs group and OPCs-alone group in motor function recovery, while the sensory function recovery was significantly promoted in OPCs combined with HUVECs groups compared with the other two groups. These findings provide novel insights into the field of SCI research.

AB - Background: Spinal cord injury (SCI) is a devastating disease that causes extensive damage to oligodendrocytes and neurons leading to demyelination and axonal degeneration. In this study, we co-transplanted cell grafts containing oligodendrocyte progenitor cells (OPCs) derived from human-induced pluripotent stem cells (iPSCs) combined with human umbilical vein endothelial cells (HUVECs), which were reported to promote OPCs survival and migration, into rat contusion models to promote functional recovery after SCI. Methods: OPCs were derived from iPSCs and identified by immunofluorescence at different time points. Functional assays in vitro were performed to evaluate the effect of HUVECs on the proliferation, migration, and survival of OPCs by co-culture and migration assay, as well as on the neuronal axonal growth. A combination of OPCs and HUVECs was transplanted into the rat contusive model. Upon 8 weeks, immunofluorescence staining was performed to test the safety of transplanted cells and to observe the neuronal repairment, myelination, and neural circuit reconstruction at the injured area; also, the functional recovery was assessed by Basso, Beattie, and Bresnahan open-field scale, Ladder climb, SEP, and MEP. Furthermore, the effect of HUVECs on grafts was also determined in vivo. Results: Data showed that HUVECs promote the proliferation, migration, and survival of OPCs both in vitro and in vivo. Furthermore, 8 weeks upon engraftment, the rats with OPCs and HUVECs co-transplantation noticeably facilitated remyelination, enhanced functional connection between the grafts and the host and promoted functional recovery. In addition, compared with the OPCs-alone transplantation, the co-transplantation generated more sensory neurons at the lesion border and significantly improved the sensory functional recovery. Conclusions: Our study demonstrates that transplantation of OPCs combined with HUVECs significantly enhances both motor and sensory functional recovery after SCI. No significance was observed between OPCs combined with HUVECs group and OPCs-alone group in motor function recovery, while the sensory function recovery was significantly promoted in OPCs combined with HUVECs groups compared with the other two groups. These findings provide novel insights into the field of SCI research.

KW - Spinal cord injury

KW - Induced pluripotent stem cells

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KW - Human Umbilical Vein Endothelial Cells

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KW - Rats

KW - Recovery of Function

KW - Spinal Cord/pathology

KW - Oligodendrocyte Precursor Cells/pathology

KW - Animals

KW - Cell Differentiation/physiology

KW - Oligodendroglia

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Grafted human-induced pluripotent stem cells-derived oligodendrocyte progenitor cells combined with human umbilical vein endothelial cells contribute to functional recovery following spinal cord injury

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