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Cited by 39Mesenchymal stem cell researchLiver physiology and pathologyLiver Disease and Transplantation

Transplantation of human bone marrow mesenchymal stromal cells reduces liver fibrosis more effectively than Wharton’s jelly mesenchymal stromal cells

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Rengasamy, Mathiyazhagan, Singh, Gurbind, Fakharuzi, Noor Atiqah, Siddikuzzaman, Balasubramanian, Sudha, Swamynathan, Priyanka, Thej, Charan, Sasidharan, Gopinath +7 more·2017·Stem Cell Research & Therapy
DOI 10.1186/s13287-017-0595-1PMC PMC5470281
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Abstract

Mesenchymal stromal cells (MSCs) from various tissues have shown moderate therapeutic efficacy in reversing liver fibrosis in preclinical models. Here, we compared the relative therapeutic potential of pooled, adult human bone marrow (BM)- and neonatal Wharton’s jelly (WJ)-derived MSCs to treat CCl 4 -induced liver fibrosis in rats. Sprague-Dawley rats were injected with CCl 4 for 8 weeks to induce irreversible liver fibrosis. Ex-vivo expanded, pooled human MSCs obtained from BM and WJ were intravenously administered into rats with liver fibrosis at a dose of 10 × 10 6 cells/animal. Sham control and vehicle-treated animals served as negative and disease controls, respectively. The animals were sacrificed at 30 and 70 days after cell transplantation and hepatic-hydroxyproline content, histopathological, and immunohistochemical analyses were performed. BM-MSCs treatment showed a marked reduction in liver fibrosis as determined by Masson’s trichrome and Sirius red staining as compared to those treated with the vehicle. Furthermore, hepatic-hydroxyproline content and percentage collagen proportionate area were found to be significantly lower in the BM-MSCs-treated group. In contrast, WJ-MSCs treatment showed less reduction of fibrosis at both time points. Immunohistochemical analysis of BM-MSCs-treated liver samples showed a reduction in α-SMA + myofibroblasts and increased number of EpCAM + hepatic progenitor cells, along with Ki-67 + and human matrix metalloprotease-1 + (MMP-1 + ) cells as compared to WJ-MSCs-treated rat livers. Our findings suggest that BM-MSCs are more effective than WJ-MSCs in treating liver fibrosis in a CCl 4 -induced model in rats. The superior therapeutic activity of BM-MSCs may be attributed to their expression of certain MMPs and angiogenic factors.

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Authors
Rengasamy, M., Singh, G., Fakharuzi, N. A., Siddikuzzaman, Balasubramanian, S., Swamynathan, P., Thej, C., Sasidharan, G., Gupta, P. K., Das, A. K., Rahman, A. Z. A., Fakiruddin, K. S., Nian, L. M., Zakaria, Z., & Majumdar, A. S.
Affiliations
  • Stempeutics (India) (IN)
  • Institute for Medical Research (MY)
  • Manipal Academy of Higher Education (IN)
Corresponding author
Majumdar, Anish S.
ORCID
Venue
Stem Cell Research & Therapy
Publisher
Springer Science and Business Media LLC
Published
2017-06-13
Volume
8
Issue
1
Pages
143-143
ISSN
1757-6512 (ISSN-L)
DOI
10.1186/s13287-017-0595-1
PMC
PMC5470281
OpenAlex
W2626328768
Cited by
39
References
0
Citations by year
2025: 4 · 2024: 2 · 2023: 6 · 2022: 2 · 2021: 7 · 2020: 7 · 2019: 8 · 2018: 1 · 2017: 2
FWCI
2.83
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Stem Cell Research & Therapy (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Greater South Information System
Funders
Institute for Medical Research (IMR), Ministry of Health, Kuala Lumpur, Malaysia and by Stempeutics Research Pvt Ltd, Bangalore. (NMRR-13-1063-18209)
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
Keywords
mesenchymal stem cells, liver fibrosis, bone marrow-derived MSCs, cell transplantation, carbon tetrachloride-induced liver injury, collagen deposition, myofibroblasts, hepatic progenitor cells, MMP-1, angiogenic factors, regenerative therapy
MeSH terms
Epithelial Cell Adhesion Molecule, Animals, Carbon Tetrachloride, Disease Models, Animal, Humans, Liver Cirrhosis, Bone Marrow Transplantation, Mesenchymal Stem Cell Transplantation, Rats, Myofibroblasts, Mesenchymal Stem Cells, Wharton Jelly

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