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...

Full description

Saved in:
Bibliographic Details
Main Authors: Jinglin Wang, Danqing Huang, Haozhen Ren, Yuanjin Zhao
Format: Article
Language:English
Published: American Association for the Advancement of Science (AAAS) 2025-01-01
Series:Research
Online Access:https://spj.science.org/doi/10.34133/research.0634
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849718542144897024
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