Injection of Ultra-Purified Stem Cells with Sodium Alginate Reduces Discogenic Pain in a Rat Model

Intervertebral disc (IVD) degeneration is a major cause of low back pain. However, treatments directly approaching the etiology of IVD degeneration and discogenic pain are not yet established. We previously demonstrated that intradiscal implantation of cell-free bioresorbable ultra-purified alginate...

Full description

Bibliographic Details
Main Authors: Hisataka Suzuki, Katsuro Ura, Daisuke Ukeba, Takashi Suyama, Norimasa Iwasaki, Masatoki Watanabe, Yumi Matsuzaki, Katsuhisa Yamada, Hideki Sudo
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/12/3/505
_version_ 1797624924567764992
author Hisataka Suzuki
Katsuro Ura
Daisuke Ukeba
Takashi Suyama
Norimasa Iwasaki
Masatoki Watanabe
Yumi Matsuzaki
Katsuhisa Yamada
Hideki Sudo
author_facet Hisataka Suzuki
Katsuro Ura
Daisuke Ukeba
Takashi Suyama
Norimasa Iwasaki
Masatoki Watanabe
Yumi Matsuzaki
Katsuhisa Yamada
Hideki Sudo
author_sort Hisataka Suzuki
collection DOAJ
description Intervertebral disc (IVD) degeneration is a major cause of low back pain. However, treatments directly approaching the etiology of IVD degeneration and discogenic pain are not yet established. We previously demonstrated that intradiscal implantation of cell-free bioresorbable ultra-purified alginate (UPAL) gel promotes tissue repair and reduces discogenic pain, and a combination of ultra-purified, Good Manufacturing Practice (GMP)-compliant, human bone marrow mesenchymal stem cells (rapidly expanding clones; RECs), and the UPAL gel increasingly enhanced IVD regeneration in animal models. This study investigated the therapeutic efficacy of injecting a mixture of REC and UPAL non-gelling solution for discogenic pain and IVD regeneration in a rat caudal nucleus pulposus punch model. REC and UPAL mixture and UPAL alone suppressed not only the expression of TNF-α, IL-6, and TrkA (<i>p</i> < 0.01, respectively), but also IVD degeneration and nociceptive behavior compared to punching alone (<i>p</i> < 0.01, respectively). Furthermore, REC and UPAL mixture suppressed these expression levels and nociceptive behavior compared to UPAL alone (<i>p</i> < 0.01, respectively). These results suggest that this minimally invasive treatment strategy with a single injection may be applied to treat discogenic pain and as a regenerative therapy.
first_indexed 2024-03-11T09:49:32Z
format Article
id doaj.art-d7f14035cc0643a9babff6749df55fd7
institution Directory Open Access Journal
issn 2073-4409
language English
last_indexed 2024-03-11T09:49:32Z
publishDate 2023-02-01
publisher MDPI AG
record_format Article
series Cells
spelling doaj.art-d7f14035cc0643a9babff6749df55fd72023-11-16T16:22:36ZengMDPI AGCells2073-44092023-02-0112350510.3390/cells12030505Injection of Ultra-Purified Stem Cells with Sodium Alginate Reduces Discogenic Pain in a Rat ModelHisataka Suzuki0Katsuro Ura1Daisuke Ukeba2Takashi Suyama3Norimasa Iwasaki4Masatoki Watanabe5Yumi Matsuzaki6Katsuhisa Yamada7Hideki Sudo8Department of Orthopedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N15W7, Sapporo 060-8638, JapanDepartment of Orthopedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N15W7, Sapporo 060-8638, JapanDepartment of Orthopedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N15W7, Sapporo 060-8638, JapanPuREC/Bio-Venture, Shimane University, Izumo 693-8501, JapanDepartment of Orthopedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N15W7, Sapporo 060-8638, JapanJapan Tissue Engineering Co., Ltd. (J-TEC), Gamagori 443-0022, JapanPuREC/Bio-Venture, Shimane University, Izumo 693-8501, JapanDepartment of Orthopedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N15W7, Sapporo 060-8638, JapanDepartment of Orthopedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N15W7, Sapporo 060-8638, JapanIntervertebral disc (IVD) degeneration is a major cause of low back pain. However, treatments directly approaching the etiology of IVD degeneration and discogenic pain are not yet established. We previously demonstrated that intradiscal implantation of cell-free bioresorbable ultra-purified alginate (UPAL) gel promotes tissue repair and reduces discogenic pain, and a combination of ultra-purified, Good Manufacturing Practice (GMP)-compliant, human bone marrow mesenchymal stem cells (rapidly expanding clones; RECs), and the UPAL gel increasingly enhanced IVD regeneration in animal models. This study investigated the therapeutic efficacy of injecting a mixture of REC and UPAL non-gelling solution for discogenic pain and IVD regeneration in a rat caudal nucleus pulposus punch model. REC and UPAL mixture and UPAL alone suppressed not only the expression of TNF-α, IL-6, and TrkA (<i>p</i> < 0.01, respectively), but also IVD degeneration and nociceptive behavior compared to punching alone (<i>p</i> < 0.01, respectively). Furthermore, REC and UPAL mixture suppressed these expression levels and nociceptive behavior compared to UPAL alone (<i>p</i> < 0.01, respectively). These results suggest that this minimally invasive treatment strategy with a single injection may be applied to treat discogenic pain and as a regenerative therapy.https://www.mdpi.com/2073-4409/12/3/505low back painintervertebral disc regenerationultra-purified clonogenic bone marrow-derived mesenchymal stem cellultra-purified alginate
spellingShingle Hisataka Suzuki
Katsuro Ura
Daisuke Ukeba
Takashi Suyama
Norimasa Iwasaki
Masatoki Watanabe
Yumi Matsuzaki
Katsuhisa Yamada
Hideki Sudo
Injection of Ultra-Purified Stem Cells with Sodium Alginate Reduces Discogenic Pain in a Rat Model
Cells
low back pain
intervertebral disc regeneration
ultra-purified clonogenic bone marrow-derived mesenchymal stem cell
ultra-purified alginate
title Injection of Ultra-Purified Stem Cells with Sodium Alginate Reduces Discogenic Pain in a Rat Model
title_full Injection of Ultra-Purified Stem Cells with Sodium Alginate Reduces Discogenic Pain in a Rat Model
title_fullStr Injection of Ultra-Purified Stem Cells with Sodium Alginate Reduces Discogenic Pain in a Rat Model
title_full_unstemmed Injection of Ultra-Purified Stem Cells with Sodium Alginate Reduces Discogenic Pain in a Rat Model
title_short Injection of Ultra-Purified Stem Cells with Sodium Alginate Reduces Discogenic Pain in a Rat Model
title_sort injection of ultra purified stem cells with sodium alginate reduces discogenic pain in a rat model
topic low back pain
intervertebral disc regeneration
ultra-purified clonogenic bone marrow-derived mesenchymal stem cell
ultra-purified alginate
url https://www.mdpi.com/2073-4409/12/3/505
work_keys_str_mv AT hisatakasuzuki injectionofultrapurifiedstemcellswithsodiumalginatereducesdiscogenicpaininaratmodel
AT katsuroura injectionofultrapurifiedstemcellswithsodiumalginatereducesdiscogenicpaininaratmodel
AT daisukeukeba injectionofultrapurifiedstemcellswithsodiumalginatereducesdiscogenicpaininaratmodel
AT takashisuyama injectionofultrapurifiedstemcellswithsodiumalginatereducesdiscogenicpaininaratmodel
AT norimasaiwasaki injectionofultrapurifiedstemcellswithsodiumalginatereducesdiscogenicpaininaratmodel
AT masatokiwatanabe injectionofultrapurifiedstemcellswithsodiumalginatereducesdiscogenicpaininaratmodel
AT yumimatsuzaki injectionofultrapurifiedstemcellswithsodiumalginatereducesdiscogenicpaininaratmodel
AT katsuhisayamada injectionofultrapurifiedstemcellswithsodiumalginatereducesdiscogenicpaininaratmodel
AT hidekisudo injectionofultrapurifiedstemcellswithsodiumalginatereducesdiscogenicpaininaratmodel