Cord blood-derived mesenchymal stem cells with hepatogenic differentiation potential ameliorate chronic liver affection in experimental models
| Autor: | Soheir Mahmoud, Ali Bayoumi, Zeinab Demerdash, Olfat Hammam, Manal Kamel, Shimaa Atta, Marwa Hassan, Wafaa Mansour, Hanan El Baz, Faten Salah, Salwa Hassan |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Liver Cirrhosis Pathology medicine.medical_specialty Medicine (miscellaneous) Mesenchymal Stem Cell Transplantation General Biochemistry Genetics and Molecular Biology Cell therapy 03 medical and health sciences Mice Fibrosis Internal Medicine medicine Animals Humans Pharmacology (medical) Genetics (clinical) business.industry Mesenchymal stem cell Cell Differentiation Mesenchymal Stem Cells Models Theoretical medicine.disease Fetal Blood Transplantation 030104 developmental biology medicine.anatomical_structure Liver Cord blood Reviews and References (medical) Hepatocytes Bone marrow Stem cell Hepatic fibrosis business |
| Zdroj: | Advances in clinical and experimental medicine : official organ Wroclaw Medical University. 27(10) |
| ISSN: | 1899-5276 |
| Popis: | BACKGROUND The liver is one of the major target organs for which cell-based therapies are very promising. The limitations of various cellular therapies, including bone marrow (BM)-derived mesenchymal stem cells (MSCs), urges the exploration of stem cell sources more suitable for transplantation. Human umbilical cord blood (HUCB) can overcome these drawbacks with a favorable reparative outcome. OBJECTIVES The aim of this study was to evaluate the therapeutic potential of MSCs in 2 groups of chronic liver injury experimental models. MATERIAL AND METHODS Propagation and characterization of MSCs isolated from cord blood (CB) samples were performed and differentiation into osteogenic, adipogenic and hepatogenic lineages was induced. The 1st experimental model group (80 mice) included a negative control, a pathological control and 60 mice infected with Schistosoma mansoni (S. mansoni) and transplanted with MSCs. The 2nd experimental model group (30 hamsters) included 10 healthy hamsters serving as a negative control and 20 hamsters injected with repeated doses of carbon tetrachloride (CCl4) to induce liver fibrosis; 10 of them were treated with an intrahepatic (IH) injection of 3 × 106 MSCs and the other 10 were untreated pathological controls. Mice and hamsters were sacrificed 12 weeks post-transplantation and their liver sections were stained immunohistochemically for the detection of human hepatocyte-like cells. Moreover, the sections were examined for the levels of fibrosis. RESULTS In both models, the transplantation of CB-derived MSCs (CB-MSCs) resulted in the engraftment of the fibrotic livers with newly formed hepatocytes, as evidenced by positive immunohistochemistry staining with human Hepatocyte Paraffin 1 (Hep Par 1), alpha-fenoprotein (AFP), cytokeratin 18 (CK18), cytokeratin 7 (CK7), and OV6 monoclonal antibody. The transplanted liver sections showed markedly reduced hepatic fibrosis with a significantly lower fibrotic index, as well as significantly improved liver functions compared to the pathological control (p < 0.001). CONCLUSIONS This data provides hope that human CB-MSCs can be utilized as multipotent stem cells with unlimited potentiality in regenerative medicine and supports the concept of cellular therapy for the cure of hepatic fibrosis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|