Effect of Stem Cell Treatment on Acute Liver Failure Model Using Scaffold

Hyeon Tae Kang, Dae Won Jung, Kiseok Jang, Jeong Kyu Hoh, Jai Sun Lee, Waqar Khalid Saeed, Yeon Ji Chae, Jin Ho Lee

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: Injecting MSCs via blood vessel is most commonly used method, which has a major drawback of safety. The aim of our study was to evaluate efficacy using scaffold-loaded MSCs in acute liver failure model. Method: Acute liver failure was induced in mice using thioacetamide (TAA) (200 mg/kg, i.p) once a day for two consecutive days. The animals were divided in four acute liver failure groups: (1) TAA; (2) empty scaffold; (3) MSCs injected through tail vein; (4) MSC + Scaffold, scaffold loaded with MSCs, to evaluate the mortality and changes in liver function. Polylactic-co-glycolic acid scaffold alone and loaded with human MSCs was implanted on mice dorsum. Results: TAA dose was titrated until one-third mortality rate was achieved. TAA (200 mg/kg) once daily for two consecutive days was injected to establish the acute liver failure model. The mortality of TAA and scaffold groups was 55.9% and 63.2%, respectively. Although, mortality of MSC-TV group decreased 14.7% as compared to TAA group (p = 0.200), MSC + Scaffold group had the lowest mortality (31.4%) (p = 0.013). Cells implanted in PLGA biomaterial were survived until 3 weeks, and their function was increased. Area of hepatic inflammation and necrosis was significantly reduced in MSC-TV and MSC + Scaffold groups; but there was no difference between the two groups. Gene expressions related to inflammation were significantly decreased in MSC-TV and MSC + Scaffold groups compared to TAA group. In MSC + Scaffold group, no migration of stem cells to liver tissue was observed. Although, not all cells in scaffold were stained, some of them were differentiated into hepatocyte-like cells which stained positive for PAS and CYP2E1 antibody. Conclusion: Scaffold loaded with MSCs showed protective effects via paracrine signaling on acute liver failure model.

Original languageEnglish
Pages (from-to)781-791
Number of pages11
JournalDigestive Diseases and Sciences
Volume64
Issue number3
DOIs
StatePublished - 2019 Mar 15

Fingerprint

Thioacetamide
Acute Liver Failure
Stem Cells
Mortality
glycolic acid
Liver
Paracrine Communication
Inflammation
Cytochrome P-450 CYP2E1
Biocompatible Materials
Blood Vessels
Tail
Hepatocytes
Veins
Necrosis
Safety
Gene Expression
Antibodies

Keywords

  • Acute liver failure
  • Mesenchymal stem cell
  • Paracrine effect
  • Scaffold

Cite this

Kang, Hyeon Tae ; Jung, Dae Won ; Jang, Kiseok ; Hoh, Jeong Kyu ; Lee, Jai Sun ; Saeed, Waqar Khalid ; Chae, Yeon Ji ; Lee, Jin Ho. / Effect of Stem Cell Treatment on Acute Liver Failure Model Using Scaffold. In: Digestive Diseases and Sciences. 2019 ; Vol. 64, No. 3. pp. 781-791.
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title = "Effect of Stem Cell Treatment on Acute Liver Failure Model Using Scaffold",
abstract = "Background: Injecting MSCs via blood vessel is most commonly used method, which has a major drawback of safety. The aim of our study was to evaluate efficacy using scaffold-loaded MSCs in acute liver failure model. Method: Acute liver failure was induced in mice using thioacetamide (TAA) (200 mg/kg, i.p) once a day for two consecutive days. The animals were divided in four acute liver failure groups: (1) TAA; (2) empty scaffold; (3) MSCs injected through tail vein; (4) MSC + Scaffold, scaffold loaded with MSCs, to evaluate the mortality and changes in liver function. Polylactic-co-glycolic acid scaffold alone and loaded with human MSCs was implanted on mice dorsum. Results: TAA dose was titrated until one-third mortality rate was achieved. TAA (200 mg/kg) once daily for two consecutive days was injected to establish the acute liver failure model. The mortality of TAA and scaffold groups was 55.9{\%} and 63.2{\%}, respectively. Although, mortality of MSC-TV group decreased 14.7{\%} as compared to TAA group (p = 0.200), MSC + Scaffold group had the lowest mortality (31.4{\%}) (p = 0.013). Cells implanted in PLGA biomaterial were survived until 3 weeks, and their function was increased. Area of hepatic inflammation and necrosis was significantly reduced in MSC-TV and MSC + Scaffold groups; but there was no difference between the two groups. Gene expressions related to inflammation were significantly decreased in MSC-TV and MSC + Scaffold groups compared to TAA group. In MSC + Scaffold group, no migration of stem cells to liver tissue was observed. Although, not all cells in scaffold were stained, some of them were differentiated into hepatocyte-like cells which stained positive for PAS and CYP2E1 antibody. Conclusion: Scaffold loaded with MSCs showed protective effects via paracrine signaling on acute liver failure model.",
keywords = "Acute liver failure, Mesenchymal stem cell, Paracrine effect, Scaffold",
author = "Kang, {Hyeon Tae} and Jung, {Dae Won} and Kiseok Jang and Hoh, {Jeong Kyu} and Lee, {Jai Sun} and Saeed, {Waqar Khalid} and Chae, {Yeon Ji} and Lee, {Jin Ho}",
year = "2019",
month = "3",
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Effect of Stem Cell Treatment on Acute Liver Failure Model Using Scaffold. / Kang, Hyeon Tae; Jung, Dae Won; Jang, Kiseok; Hoh, Jeong Kyu; Lee, Jai Sun; Saeed, Waqar Khalid; Chae, Yeon Ji; Lee, Jin Ho.

In: Digestive Diseases and Sciences, Vol. 64, No. 3, 15.03.2019, p. 781-791.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Effect of Stem Cell Treatment on Acute Liver Failure Model Using Scaffold

AU - Kang, Hyeon Tae

AU - Jung, Dae Won

AU - Jang, Kiseok

AU - Hoh, Jeong Kyu

AU - Lee, Jai Sun

AU - Saeed, Waqar Khalid

AU - Chae, Yeon Ji

AU - Lee, Jin Ho

PY - 2019/3/15

Y1 - 2019/3/15

N2 - Background: Injecting MSCs via blood vessel is most commonly used method, which has a major drawback of safety. The aim of our study was to evaluate efficacy using scaffold-loaded MSCs in acute liver failure model. Method: Acute liver failure was induced in mice using thioacetamide (TAA) (200 mg/kg, i.p) once a day for two consecutive days. The animals were divided in four acute liver failure groups: (1) TAA; (2) empty scaffold; (3) MSCs injected through tail vein; (4) MSC + Scaffold, scaffold loaded with MSCs, to evaluate the mortality and changes in liver function. Polylactic-co-glycolic acid scaffold alone and loaded with human MSCs was implanted on mice dorsum. Results: TAA dose was titrated until one-third mortality rate was achieved. TAA (200 mg/kg) once daily for two consecutive days was injected to establish the acute liver failure model. The mortality of TAA and scaffold groups was 55.9% and 63.2%, respectively. Although, mortality of MSC-TV group decreased 14.7% as compared to TAA group (p = 0.200), MSC + Scaffold group had the lowest mortality (31.4%) (p = 0.013). Cells implanted in PLGA biomaterial were survived until 3 weeks, and their function was increased. Area of hepatic inflammation and necrosis was significantly reduced in MSC-TV and MSC + Scaffold groups; but there was no difference between the two groups. Gene expressions related to inflammation were significantly decreased in MSC-TV and MSC + Scaffold groups compared to TAA group. In MSC + Scaffold group, no migration of stem cells to liver tissue was observed. Although, not all cells in scaffold were stained, some of them were differentiated into hepatocyte-like cells which stained positive for PAS and CYP2E1 antibody. Conclusion: Scaffold loaded with MSCs showed protective effects via paracrine signaling on acute liver failure model.

AB - Background: Injecting MSCs via blood vessel is most commonly used method, which has a major drawback of safety. The aim of our study was to evaluate efficacy using scaffold-loaded MSCs in acute liver failure model. Method: Acute liver failure was induced in mice using thioacetamide (TAA) (200 mg/kg, i.p) once a day for two consecutive days. The animals were divided in four acute liver failure groups: (1) TAA; (2) empty scaffold; (3) MSCs injected through tail vein; (4) MSC + Scaffold, scaffold loaded with MSCs, to evaluate the mortality and changes in liver function. Polylactic-co-glycolic acid scaffold alone and loaded with human MSCs was implanted on mice dorsum. Results: TAA dose was titrated until one-third mortality rate was achieved. TAA (200 mg/kg) once daily for two consecutive days was injected to establish the acute liver failure model. The mortality of TAA and scaffold groups was 55.9% and 63.2%, respectively. Although, mortality of MSC-TV group decreased 14.7% as compared to TAA group (p = 0.200), MSC + Scaffold group had the lowest mortality (31.4%) (p = 0.013). Cells implanted in PLGA biomaterial were survived until 3 weeks, and their function was increased. Area of hepatic inflammation and necrosis was significantly reduced in MSC-TV and MSC + Scaffold groups; but there was no difference between the two groups. Gene expressions related to inflammation were significantly decreased in MSC-TV and MSC + Scaffold groups compared to TAA group. In MSC + Scaffold group, no migration of stem cells to liver tissue was observed. Although, not all cells in scaffold were stained, some of them were differentiated into hepatocyte-like cells which stained positive for PAS and CYP2E1 antibody. Conclusion: Scaffold loaded with MSCs showed protective effects via paracrine signaling on acute liver failure model.

KW - Acute liver failure

KW - Mesenchymal stem cell

KW - Paracrine effect

KW - Scaffold

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U2 - 10.1007/s10620-018-5363-2

DO - 10.1007/s10620-018-5363-2

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