TY - JOUR
T1 - Intravenous injection of umbilical cord-derived mesenchymal stem cells improved regeneration of rat liver after 2aaf/ccl4-induced injury
AU - Liem, Isabella Kurnia
AU - Oktavina, Reni
AU - Zakiyah,
AU - Anggraini, Dian
AU - Deraya, Irwina Eka
AU - Kodariah, Ria
AU - Krisnuhoni, Ening
AU - Wuyung, Puspita Eka
N1 - Funding Information:
We thank Firda Asma’ul Husna and Ayu Eka Fatril for fascilitating the manuscript preparation and continuation of the research. This research was supported by grant aid from Penelitian Dasar Unggulan Perguruan Tinggi (PDUPT) year 2020.
Publisher Copyright:
© 2021 Isabella Kurnia Liem, Reni Oktavina, Zakiyah, Dian Anggraini, Irwina Eka Deraya, Ria Kodariah, Ening Krisnuhoni, and Puspita Eka Wuyung.
PY - 2021
Y1 - 2021
N2 - The effectivity of Mesenchymal Stem Cell (MSC) therapy for chronic liver injury is still questioned due to its possibility to have a pro-fibrotic effects. Other consideration is the preferably peripheral Intravenous (IV) route of application rather than direct to the target organ, such as portal vein or splenic vein, since the most of MSC will be trapped in the lung and other organs. Therefore, a study has been carried out in an animal model of chronic liver injury, 2AAF/CCl4 rats, to find out whether IV injection of single dose, 1×106 human umbilical cord-derived MSC (hUC-MSC) can regenerate the liver tissue and reduce the fibrosis. Male Wistar rats (n = 18, 8 weeks, 160-200 g) were divided into three groups of six rats, i.e., group I (control/healthy rats), group II (2AAF/CCl4-induced liver injury with hUC-MSC injected rats) and group III (2AAF/CCl4-incuded liver injury without hUC-MSC injected rats). Gross anatomical features of the livers and blood examination were tested. There was no significant different of the Alanine Aminotransferase (ALT) and Albumin serum level between groups; however there was a tendency of ALT decrease and Albumin increase in stem cells treated rats (group II). Histopathological observation using hematoxylin eosin and Masson’s trichrome staining showed an improvement in the liver damage condition (reduction of necrosis and coverage area of fat degeneration) and an improvement in the fibrosis condition in the group II compared to the group III. None of group II rat had fallen into cirrhosis as seen in group III. Immunohistochemistry staining against Caspase 3 (biomarker for apoptosis) also showed significant reduction (p = 0.038; Tukey multiple comparison test) of group II expression index (2.74%) compared to the group III (8.64%). In conclusion, IV injection of single dose, 1×106 hUC-MSC could regenerate the liver tissue and reduce the fibrosis in 2AAF/CCl4 rats model of chronic liver injury.
AB - The effectivity of Mesenchymal Stem Cell (MSC) therapy for chronic liver injury is still questioned due to its possibility to have a pro-fibrotic effects. Other consideration is the preferably peripheral Intravenous (IV) route of application rather than direct to the target organ, such as portal vein or splenic vein, since the most of MSC will be trapped in the lung and other organs. Therefore, a study has been carried out in an animal model of chronic liver injury, 2AAF/CCl4 rats, to find out whether IV injection of single dose, 1×106 human umbilical cord-derived MSC (hUC-MSC) can regenerate the liver tissue and reduce the fibrosis. Male Wistar rats (n = 18, 8 weeks, 160-200 g) were divided into three groups of six rats, i.e., group I (control/healthy rats), group II (2AAF/CCl4-induced liver injury with hUC-MSC injected rats) and group III (2AAF/CCl4-incuded liver injury without hUC-MSC injected rats). Gross anatomical features of the livers and blood examination were tested. There was no significant different of the Alanine Aminotransferase (ALT) and Albumin serum level between groups; however there was a tendency of ALT decrease and Albumin increase in stem cells treated rats (group II). Histopathological observation using hematoxylin eosin and Masson’s trichrome staining showed an improvement in the liver damage condition (reduction of necrosis and coverage area of fat degeneration) and an improvement in the fibrosis condition in the group II compared to the group III. None of group II rat had fallen into cirrhosis as seen in group III. Immunohistochemistry staining against Caspase 3 (biomarker for apoptosis) also showed significant reduction (p = 0.038; Tukey multiple comparison test) of group II expression index (2.74%) compared to the group III (8.64%). In conclusion, IV injection of single dose, 1×106 hUC-MSC could regenerate the liver tissue and reduce the fibrosis in 2AAF/CCl4 rats model of chronic liver injury.
KW - 2AAF/CCl
KW - Caspase 3
KW - Liver Fibrosis
KW - Liver Injury
KW - Liver Regeneration
KW - MSC
UR - http://www.scopus.com/inward/record.url?scp=85108885347&partnerID=8YFLogxK
U2 - 10.3844/ojbsci.2021.317.326
DO - 10.3844/ojbsci.2021.317.326
M3 - Article
AN - SCOPUS:85108885347
VL - 21
SP - 317
EP - 326
JO - OnLine Journal of Biological Sciences
JF - OnLine Journal of Biological Sciences
SN - 1608-4217
IS - 2
ER -