Transplantation of chemically induced liver progenitors in Nagase analbuminemic rats under liver regenerative stimulus
We have explored chemically induced liver progenitors (CLiP) as a potential therapeutic agent for liver diseases because their proliferative capacity in vitro. Therefore, we hypothesized the potential treatment with CLiP transplantation (Tx) could be effective and be enhanced with liver regenerative...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-12-01
|
| Series: | Regenerative Therapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352320425000914 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849729502273339392 |
|---|---|
| author | Masayuki Fukumoto Akihiko Soyama Daisuke Miyamoto Takanobu Hara Hajime Matsushima Hajime Imamura Mampei Yamashita Tomohiko Adachi Kengo Kanetaka Susumu Eguchi |
| author_facet | Masayuki Fukumoto Akihiko Soyama Daisuke Miyamoto Takanobu Hara Hajime Matsushima Hajime Imamura Mampei Yamashita Tomohiko Adachi Kengo Kanetaka Susumu Eguchi |
| author_sort | Masayuki Fukumoto |
| collection | DOAJ |
| description | We have explored chemically induced liver progenitors (CLiP) as a potential therapeutic agent for liver diseases because their proliferative capacity in vitro. Therefore, we hypothesized the potential treatment with CLiP transplantation (Tx) could be effective and be enhanced with liver regenerative stimulus for metabolic liver diseases. Methods: Male Sprague Dawley rats were used for mature hepatocytes (HEP) isolation to induce CLiP using 3 small molecules cocktail (ROCK-inhibitor, TGF beta-1 inhibitor, GSK3 inhibitor). Harvested rat CLiP (1 × 106) were transplanted to the posterior lobe of the liver (30 % of whole liver) of Nagase analbuminemic rats (NAR) through portal vein injection. One week later, portal venous branch to non-transplanted lobe was ligated to induce liver regeneration in CLiP bearing liver lobe (portal branch ligation: PBL). Only CLiP Tx or HEP Tx of same dose were used as control groups. Serial measurement of serum albumin level was measured by ELISA method. All NARs were subject to immunosuppression therapy using tacrolimus s.q. 3 days per week. Results: After HEP Tx especially with PBL, serum albumin level was significantly elevated. However, even with PBL, CLiP Tx group did not show significant increase in serum albumin. CLiP were surrounded by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) positive cells in portal veins suggesting that CLiP were exposed to the risk of innate immunity. Conclusion: Although CLiP respond to growth factors and proliferate better than HEP in vitro, their behavior in vivo in response to liver regenerative stimulus were not similar to in vitro probably because of less immaturity of receptors and/or high immunogenicity as compared to HEP. |
| format | Article |
| id | doaj-art-e240d1db926c483591bd27ecfd2fe18c |
| institution | DOAJ |
| issn | 2352-3204 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Regenerative Therapy |
| spelling | doaj-art-e240d1db926c483591bd27ecfd2fe18c2025-08-20T03:09:12ZengElsevierRegenerative Therapy2352-32042025-12-01301810.1016/j.reth.2025.04.015Transplantation of chemically induced liver progenitors in Nagase analbuminemic rats under liver regenerative stimulusMasayuki Fukumoto0Akihiko Soyama1Daisuke Miyamoto2Takanobu Hara3Hajime Matsushima4Hajime Imamura5Mampei Yamashita6Tomohiko Adachi7Kengo Kanetaka8Susumu Eguchi9Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501 JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501 JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501 JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501 JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501 JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501 JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501 JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501 JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501 JapanCorresponding author.; Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501 JapanWe have explored chemically induced liver progenitors (CLiP) as a potential therapeutic agent for liver diseases because their proliferative capacity in vitro. Therefore, we hypothesized the potential treatment with CLiP transplantation (Tx) could be effective and be enhanced with liver regenerative stimulus for metabolic liver diseases. Methods: Male Sprague Dawley rats were used for mature hepatocytes (HEP) isolation to induce CLiP using 3 small molecules cocktail (ROCK-inhibitor, TGF beta-1 inhibitor, GSK3 inhibitor). Harvested rat CLiP (1 × 106) were transplanted to the posterior lobe of the liver (30 % of whole liver) of Nagase analbuminemic rats (NAR) through portal vein injection. One week later, portal venous branch to non-transplanted lobe was ligated to induce liver regeneration in CLiP bearing liver lobe (portal branch ligation: PBL). Only CLiP Tx or HEP Tx of same dose were used as control groups. Serial measurement of serum albumin level was measured by ELISA method. All NARs were subject to immunosuppression therapy using tacrolimus s.q. 3 days per week. Results: After HEP Tx especially with PBL, serum albumin level was significantly elevated. However, even with PBL, CLiP Tx group did not show significant increase in serum albumin. CLiP were surrounded by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) positive cells in portal veins suggesting that CLiP were exposed to the risk of innate immunity. Conclusion: Although CLiP respond to growth factors and proliferate better than HEP in vitro, their behavior in vivo in response to liver regenerative stimulus were not similar to in vitro probably because of less immaturity of receptors and/or high immunogenicity as compared to HEP.http://www.sciencedirect.com/science/article/pii/S2352320425000914Chemically induced liver progenitorTransplantationLiver regenerationAlbuminTRAIL |
| spellingShingle | Masayuki Fukumoto Akihiko Soyama Daisuke Miyamoto Takanobu Hara Hajime Matsushima Hajime Imamura Mampei Yamashita Tomohiko Adachi Kengo Kanetaka Susumu Eguchi Transplantation of chemically induced liver progenitors in Nagase analbuminemic rats under liver regenerative stimulus Regenerative Therapy Chemically induced liver progenitor Transplantation Liver regeneration Albumin TRAIL |
| title | Transplantation of chemically induced liver progenitors in Nagase analbuminemic rats under liver regenerative stimulus |
| title_full | Transplantation of chemically induced liver progenitors in Nagase analbuminemic rats under liver regenerative stimulus |
| title_fullStr | Transplantation of chemically induced liver progenitors in Nagase analbuminemic rats under liver regenerative stimulus |
| title_full_unstemmed | Transplantation of chemically induced liver progenitors in Nagase analbuminemic rats under liver regenerative stimulus |
| title_short | Transplantation of chemically induced liver progenitors in Nagase analbuminemic rats under liver regenerative stimulus |
| title_sort | transplantation of chemically induced liver progenitors in nagase analbuminemic rats under liver regenerative stimulus |
| topic | Chemically induced liver progenitor Transplantation Liver regeneration Albumin TRAIL |
| url | http://www.sciencedirect.com/science/article/pii/S2352320425000914 |
| work_keys_str_mv | AT masayukifukumoto transplantationofchemicallyinducedliverprogenitorsinnagaseanalbuminemicratsunderliverregenerativestimulus AT akihikosoyama transplantationofchemicallyinducedliverprogenitorsinnagaseanalbuminemicratsunderliverregenerativestimulus AT daisukemiyamoto transplantationofchemicallyinducedliverprogenitorsinnagaseanalbuminemicratsunderliverregenerativestimulus AT takanobuhara transplantationofchemicallyinducedliverprogenitorsinnagaseanalbuminemicratsunderliverregenerativestimulus AT hajimematsushima transplantationofchemicallyinducedliverprogenitorsinnagaseanalbuminemicratsunderliverregenerativestimulus AT hajimeimamura transplantationofchemicallyinducedliverprogenitorsinnagaseanalbuminemicratsunderliverregenerativestimulus AT mampeiyamashita transplantationofchemicallyinducedliverprogenitorsinnagaseanalbuminemicratsunderliverregenerativestimulus AT tomohikoadachi transplantationofchemicallyinducedliverprogenitorsinnagaseanalbuminemicratsunderliverregenerativestimulus AT kengokanetaka transplantationofchemicallyinducedliverprogenitorsinnagaseanalbuminemicratsunderliverregenerativestimulus AT susumueguchi transplantationofchemicallyinducedliverprogenitorsinnagaseanalbuminemicratsunderliverregenerativestimulus |