Bioinspired Spatially Ordered Multicellular Lobules for Liver Regeneration
Cell therapy is a promising strategy for acute liver failure (ALF), while its therapeutic efficacy is often limited by cell loss and poor arrangement. Here, inspired by liver microunits, we propose a novel spatially ordered multicellular lobules for the ALF treatment by using a microfluidic continuo...
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| Format: | Article |
| Language: | English |
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American Association for the Advancement of Science (AAAS)
2025-01-01
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| Series: | Research |
| Online Access: | https://spj.science.org/doi/10.34133/research.0634 |
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| author | Jinglin Wang Danqing Huang Haozhen Ren Yuanjin Zhao |
| author_facet | Jinglin Wang Danqing Huang Haozhen Ren Yuanjin Zhao |
| author_sort | Jinglin Wang |
| collection | DOAJ |
| description | Cell therapy is a promising strategy for acute liver failure (ALF), while its therapeutic efficacy is often limited by cell loss and poor arrangement. Here, inspired by liver microunits, we propose a novel spatially ordered multicellular lobules for the ALF treatment by using a microfluidic continuous spinning technology. The microfluidics with multiple microchannels was constructed by assembling parallel capillaries. Sodium alginate (Alg) solution encapsulating human umbilical vein endothelial cells (HUVECs), hepatocytes, and mesenchymal stem cells (MSCs) are introduced into the middle channel and the 6 parallel outer channels of the microfluidics, respectively. Simultaneously, Ca2+-loaded solutions are pumped through the innermost and outermost channels, forming a hollow microfiber with hepatocytes and MSCs alternately surrounding the HUVECs. These microfibers could highly resemble the cord-like structure of liver lobules, bringing about outstanding liver-like functions. We have demonstrated that in ALF rats, our biomimetic lobules can effectively suppress excessive inflammatory responses, decrease cell necrosis, and promote regenerative pathways, leading to satisfied therapeutic efficacy. These findings underscore the potential of spatially ordered multicellular microfibers in treating related diseases and improving traditional clinical methods. |
| format | Article |
| id | doaj-art-61f4e17835904ce99d6652dc57069c13 |
| institution | DOAJ |
| issn | 2639-5274 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | Article |
| series | Research |
| spelling | doaj-art-61f4e17835904ce99d6652dc57069c132025-08-20T03:12:20ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742025-01-01810.34133/research.0634Bioinspired Spatially Ordered Multicellular Lobules for Liver RegenerationJinglin Wang0Danqing Huang1Haozhen Ren2Yuanjin Zhao3Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China.Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China.Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China.Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China.Cell therapy is a promising strategy for acute liver failure (ALF), while its therapeutic efficacy is often limited by cell loss and poor arrangement. Here, inspired by liver microunits, we propose a novel spatially ordered multicellular lobules for the ALF treatment by using a microfluidic continuous spinning technology. The microfluidics with multiple microchannels was constructed by assembling parallel capillaries. Sodium alginate (Alg) solution encapsulating human umbilical vein endothelial cells (HUVECs), hepatocytes, and mesenchymal stem cells (MSCs) are introduced into the middle channel and the 6 parallel outer channels of the microfluidics, respectively. Simultaneously, Ca2+-loaded solutions are pumped through the innermost and outermost channels, forming a hollow microfiber with hepatocytes and MSCs alternately surrounding the HUVECs. These microfibers could highly resemble the cord-like structure of liver lobules, bringing about outstanding liver-like functions. We have demonstrated that in ALF rats, our biomimetic lobules can effectively suppress excessive inflammatory responses, decrease cell necrosis, and promote regenerative pathways, leading to satisfied therapeutic efficacy. These findings underscore the potential of spatially ordered multicellular microfibers in treating related diseases and improving traditional clinical methods.https://spj.science.org/doi/10.34133/research.0634 |
| spellingShingle | Jinglin Wang Danqing Huang Haozhen Ren Yuanjin Zhao Bioinspired Spatially Ordered Multicellular Lobules for Liver Regeneration Research |
| title | Bioinspired Spatially Ordered Multicellular Lobules for Liver Regeneration |
| title_full | Bioinspired Spatially Ordered Multicellular Lobules for Liver Regeneration |
| title_fullStr | Bioinspired Spatially Ordered Multicellular Lobules for Liver Regeneration |
| title_full_unstemmed | Bioinspired Spatially Ordered Multicellular Lobules for Liver Regeneration |
| title_short | Bioinspired Spatially Ordered Multicellular Lobules for Liver Regeneration |
| title_sort | bioinspired spatially ordered multicellular lobules for liver regeneration |
| url | https://spj.science.org/doi/10.34133/research.0634 |
| work_keys_str_mv | AT jinglinwang bioinspiredspatiallyorderedmulticellularlobulesforliverregeneration AT danqinghuang bioinspiredspatiallyorderedmulticellularlobulesforliverregeneration AT haozhenren bioinspiredspatiallyorderedmulticellularlobulesforliverregeneration AT yuanjinzhao bioinspiredspatiallyorderedmulticellularlobulesforliverregeneration |