3D spheroids of human placenta-derived mesenchymal stem cells attenuate spinal cord injury in mice

Abstract Mesenchymal stem cell (MSC) is an absorbing candidate for cell therapy in treating spinal cord injury (SCI) due to its great potential for multiple cell differentiation, mighty paracrine secretion as well as vigorous immunomodulatory effect, of which are beneficial to the improvement of fun...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Junhao Deng, Miao Li, Fanqi Meng, Zhongyang Liu, Song Wang, Yuan Zhang, Ming Li, Zhirui Li, Licheng Zhang, Peifu Tang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/6481c7cb30f348e8a751659d7d144b74
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6481c7cb30f348e8a751659d7d144b74
record_format	dspace
spelling	oai:doaj.org-article:6481c7cb30f348e8a751659d7d144b742021-11-28T12:04:34Z3D spheroids of human placenta-derived mesenchymal stem cells attenuate spinal cord injury in mice10.1038/s41419-021-04398-w2041-4889https://doaj.org/article/6481c7cb30f348e8a751659d7d144b742021-11-01T00:00:00Zhttps://doi.org/10.1038/s41419-021-04398-whttps://doaj.org/toc/2041-4889Abstract Mesenchymal stem cell (MSC) is an absorbing candidate for cell therapy in treating spinal cord injury (SCI) due to its great potential for multiple cell differentiation, mighty paracrine secretion as well as vigorous immunomodulatory effect, of which are beneficial to the improvement of functional recovery post SCI. However, the therapeutic effects of MSC on SCI have been limited because of the gradual loss of MSC stemness in the process of expanding culture. Therefore, in this study, we aimed to maintain those beneficial properties of MSC via three-dimensional spheroid cell culture and then compared them with conventionally-cultured MSCs in the treatment of SCI both in vitro and in vivo with the aid of two-photon microscope. We found that 3D human placenta-derived MSCs (3D-HPMSCs) demonstrated a significant increase in secretion of anti-inflammatory factors and trophic factors like VEGF, PDGF, FGF via QPCR and Bio-Plex assays, and showed great potentials on angiogenesis and neurite morphogenesis when co-cultured with HUVECs or DRGs in vitro. After transplantation into the injured spinal cord, 3D-HPMSCs managed to survive for the entire experiment and retained their advantageous properties in secretion, and exhibited remarkable effects on neuroprotection by minimizing the lesion cavity, inhibiting the inflammation and astrogliosis, and promoting angiogenesis. Further investigation of axonal dieback via two-photon microscope indicated that 3D-HPMSCs could effectively alleviate axonal dieback post injury. Further, mice only treated with 3D-HPMSCs obtained substantial improvement of functional recovery on electrophysiology, BMS score, and Catwalk analysis. RNA sequencing suggested that the 3D-HPMSCs structure organization-related gene was significantly changed, which was likely to potentiate the angiogenesis and inflammation regulation after SCI. These results suggest that 3D-HPMSCs may hold great potential for the treatment of SCI.Junhao DengMiao LiFanqi MengZhongyang LiuSong WangYuan ZhangMing LiZhirui LiLicheng ZhangPeifu TangNature Publishing GrouparticleCytologyQH573-671ENCell Death and Disease, Vol 12, Iss 12, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Junhao Deng Miao Li Fanqi Meng Zhongyang Liu Song Wang Yuan Zhang Ming Li Zhirui Li Licheng Zhang Peifu Tang 3D spheroids of human placenta-derived mesenchymal stem cells attenuate spinal cord injury in mice
description	Abstract Mesenchymal stem cell (MSC) is an absorbing candidate for cell therapy in treating spinal cord injury (SCI) due to its great potential for multiple cell differentiation, mighty paracrine secretion as well as vigorous immunomodulatory effect, of which are beneficial to the improvement of functional recovery post SCI. However, the therapeutic effects of MSC on SCI have been limited because of the gradual loss of MSC stemness in the process of expanding culture. Therefore, in this study, we aimed to maintain those beneficial properties of MSC via three-dimensional spheroid cell culture and then compared them with conventionally-cultured MSCs in the treatment of SCI both in vitro and in vivo with the aid of two-photon microscope. We found that 3D human placenta-derived MSCs (3D-HPMSCs) demonstrated a significant increase in secretion of anti-inflammatory factors and trophic factors like VEGF, PDGF, FGF via QPCR and Bio-Plex assays, and showed great potentials on angiogenesis and neurite morphogenesis when co-cultured with HUVECs or DRGs in vitro. After transplantation into the injured spinal cord, 3D-HPMSCs managed to survive for the entire experiment and retained their advantageous properties in secretion, and exhibited remarkable effects on neuroprotection by minimizing the lesion cavity, inhibiting the inflammation and astrogliosis, and promoting angiogenesis. Further investigation of axonal dieback via two-photon microscope indicated that 3D-HPMSCs could effectively alleviate axonal dieback post injury. Further, mice only treated with 3D-HPMSCs obtained substantial improvement of functional recovery on electrophysiology, BMS score, and Catwalk analysis. RNA sequencing suggested that the 3D-HPMSCs structure organization-related gene was significantly changed, which was likely to potentiate the angiogenesis and inflammation regulation after SCI. These results suggest that 3D-HPMSCs may hold great potential for the treatment of SCI.
format	article
author	Junhao Deng Miao Li Fanqi Meng Zhongyang Liu Song Wang Yuan Zhang Ming Li Zhirui Li Licheng Zhang Peifu Tang
author_facet	Junhao Deng Miao Li Fanqi Meng Zhongyang Liu Song Wang Yuan Zhang Ming Li Zhirui Li Licheng Zhang Peifu Tang
author_sort	Junhao Deng
title	3D spheroids of human placenta-derived mesenchymal stem cells attenuate spinal cord injury in mice
title_short	3D spheroids of human placenta-derived mesenchymal stem cells attenuate spinal cord injury in mice
title_full	3D spheroids of human placenta-derived mesenchymal stem cells attenuate spinal cord injury in mice
title_fullStr	3D spheroids of human placenta-derived mesenchymal stem cells attenuate spinal cord injury in mice
title_full_unstemmed	3D spheroids of human placenta-derived mesenchymal stem cells attenuate spinal cord injury in mice
title_sort	3d spheroids of human placenta-derived mesenchymal stem cells attenuate spinal cord injury in mice
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/6481c7cb30f348e8a751659d7d144b74
work_keys_str_mv	AT junhaodeng 3dspheroidsofhumanplacentaderivedmesenchymalstemcellsattenuatespinalcordinjuryinmice AT miaoli 3dspheroidsofhumanplacentaderivedmesenchymalstemcellsattenuatespinalcordinjuryinmice AT fanqimeng 3dspheroidsofhumanplacentaderivedmesenchymalstemcellsattenuatespinalcordinjuryinmice AT zhongyangliu 3dspheroidsofhumanplacentaderivedmesenchymalstemcellsattenuatespinalcordinjuryinmice AT songwang 3dspheroidsofhumanplacentaderivedmesenchymalstemcellsattenuatespinalcordinjuryinmice AT yuanzhang 3dspheroidsofhumanplacentaderivedmesenchymalstemcellsattenuatespinalcordinjuryinmice AT mingli 3dspheroidsofhumanplacentaderivedmesenchymalstemcellsattenuatespinalcordinjuryinmice AT zhiruili 3dspheroidsofhumanplacentaderivedmesenchymalstemcellsattenuatespinalcordinjuryinmice AT lichengzhang 3dspheroidsofhumanplacentaderivedmesenchymalstemcellsattenuatespinalcordinjuryinmice AT peifutang 3dspheroidsofhumanplacentaderivedmesenchymalstemcellsattenuatespinalcordinjuryinmice
_version_	1718408201294053376

3D spheroids of human placenta-derived mesenchymal stem cells attenuate spinal cord injury in mice

Ejemplares similares