An ultrastructural quantitative assessment of hepatic stellate cells (HSCs) was made in relation ... more An ultrastructural quantitative assessment of hepatic stellate cells (HSCs) was made in relation to hepatic fibrosis, apoptotic cellular changes, intracellular fat deposition, circulating inflammatory cells in the sinusoids, and the necroinflammatory activity in liver specimens of 33 patients proven to be positive for hepatitis C virus (HCV)-RNA by polymerase chain reaction with the intention that electron microscopy may throw more light on the role of HSCs in the complicated process of fibrogenesis. A detailed review concerning these parameters and observed evidence suggesting the potential properties of HSCs to recycle cellular debris into collagen fibers are reported.
The in vivo angiogenic potential of transplanted human umbilical cord blood (UCB) CD133(+) stem c... more The in vivo angiogenic potential of transplanted human umbilical cord blood (UCB) CD133(+) stem cells in experimental chronic hepatic fibrosis induced by murine schistosomiasis was studied. Enriched cord blood-derived CD133(+) cells were cultured in primary medium for 3 weeks. Twenty-two weeks post-Schistosomiasis infection in mice, after reaching the chronic hepatic fibrotic stage, transplantation of stem cells was performed and mice were sacrificed 3 weeks later. Histopathology and electron microscopy showed an increase in newly formed blood vessels and a decrease in the fibrosis known for this stage of the disease. By immunohistochemical analysis the newly formed blood vessels showed positive expression of the human-specific angiogenic markers CD31, CD34 and von Willebrand factor. Few hepatocyte-like polygonal cells showed positive expression of human vascular endothelial growth factor and inducible nitric oxide synthase. The transplanted CD133(+) human stem cells primarily enhanced hepatic angiogenesis and neovascularization and contributed to repair in a paracrine manner by creating a permissive environment that enabled proliferation and survival of damaged cells rather than by direct differentiation to hepatocytes. A dual advantage of CD133(+) cell therapy in hepatic disease is suggested based on its capability of hematopoietic and endothelial differentiation.
Background Anthelminthic treatment options against schistosomiasis are limited. The current treat... more Background Anthelminthic treatment options against schistosomiasis are limited. The current treatment relies almost exclusively on a single drug, praziquantel (PZQ). As a consequence, the development of resistance to PZQ and limited activity of PZQ against earlier development stages are respectively a risk and a limitation to achieving the goals of the new WHO roadmap towards elimination. For the discovery of new chemical starting points, the in vitro drug screening on Schistosoma mansoni (S. mansoni) against newly transformed schistosomula (NTS) is still the most predominant approach. The use of only NTS in the initial screening limits sensitivity to potential new compounds which are predominantly active in later developmental stages. Using our recently described highly standardized, straightforward and reliable culture method that generates high rates of juvenile worms, we aimed to repurpose a subset of the National Center for Advancing Translational Sciences (NCATS) Pharmaceutica...
The efficiency of differentiation of bone marrow cells (BMCs) into hepatocytes in vivo and its im... more The efficiency of differentiation of bone marrow cells (BMCs) into hepatocytes in vivo and its importance in physiopathological processes is still debated. Murine schistosomiasis was used as a liver injury model and unfractionated male mice BMCs were transplanted through intrahepatic injection into non-irradiated Schistosoma mansoni-infected female mice on their 16th week post-infection. Two weeks after bone marrow transplantation, mice were sacrificed on a weekly basis until 10 weeks. Tracing of male donor-derived cells in female recipient mice livers was carried out by the detection of Y chromosome expression by fluorescent in situ hybridization (FISH) and also of chromodomain Y-linked (CDYL) protein by indirect immunofluorescence (IF). Their transformation into hepatocytes was studied by double labelling indirect IF using antibodies directed against CDYL and mouse albumin. Histopathological and electron microscopic examinations revealed the presence of small hepatocyte-like cells in the periportal tracts and in between the hepatocytes facing the sinusoids. Donor-derived cells showing Y chromosome by FISH and expressing CDYL protein by IF were recovered in the infected transplanted livers. The initial number of these cells increased with increased post-transplantation time. Cells were mainly localized in the periphery of schistosoma granuloma. Few donor-derived cells appeared within the hepatic parenchymal tissue and showed positivity for albumin secretion by double labelling with IF. We suggest that transplanted bone marrow stem cells can repopulate the Schistosoma-infected liver of immunocompetent mice. Their differentiation is a complex event controlled by many factors and needs to be further characterized extensively. The extent and type of liver injury and the number of transplanted cells are important variables in the process of stem cell engraftment and differentiation into functioning hepatic cells that still need to be defined.
Liver fibrosis is one of the most serious consequences of S. mansoni infection. The aim of the pr... more Liver fibrosis is one of the most serious consequences of S. mansoni infection. The aim of the present study was to investigate the potential anti-fibrotic effect of human Wharton’s jelly-derived mesenchymal stem cells (WJMSCs) combined with praziquantel (PZQ) in S. mansoni-infected mice. S. mansoni-infected mice received early (8th week post infection) and late (16th week post infection) treatment with WJMSCs, alone and combined with oral PZQ. At the 10th month post infection, livers were collected for subsequent flow cytometric, histopathological, morphometric, immunohistochemical, gene expression, and gelatin zymographic studies. After transplantation, WJMSCs differentiated into functioning liver-like cells as evidenced by their ability to express human hepatocyte-specific markers. Regression of S. mansoni-induced liver fibrosis was also observed in transplanted groups, as evidenced by histopathological, morphometric, and gelatin zymographic results besides decreased expression o...
One of the most serious consequences of Schistosoma ( S. ) mansoni infection is hepatic schistoso... more One of the most serious consequences of Schistosoma ( S. ) mansoni infection is hepatic schistosomiasis or periportal fibrosis. Treatment with praziquantel (PZQ) remains the mainstay of schistosomiasis control. Stem cells and their possible use in cell therapy have drawn much attention recently, due to their potential for self - renewal and differentiation. The present study aimed to investigate the ability of mesenchymal stem cells (MSCs) to integrate into the livers of S. mansoni - infected mice. S. mansoni - infected mice (60±10 cercariae/mouse, s.c.) received intra hepatic i njection of MSCs (1.5x10 6 cells/mouse), alone or combined with oral PZQ (500 mg/kg/day, for 2 days, seven weeks post infection). At the 10 th month post infection, flow cytometry and immunohistochemical analysis for human - specific β2 - globulin were performed . Immunohistochemical results showed positive hepatic expression for β2 - globulin. Interestingly, the integration of MSCs was found to be enhanced ...
ABSTRACT Wharton's jelly (WJ) is a gelatinous tissue within the umbilical cord that conta... more ABSTRACT Wharton's jelly (WJ) is a gelatinous tissue within the umbilical cord that contains myofibroblast-like stromal cells. A unique cell population of WJ that has been suggested as displaying the stemness phenotype is the mesenchymal stromal cells (MSCs). Because MSCs' stemness and immune properties appear to be more robustly expressed and functional which are more comparable with fetal than adult-derived MSCs, MSCs harvested from the "young" WJ are considered much more proliferative, immunosuppressive, and even therapeutically active stem cells than those isolated from older, adult tissue sources such as the bone marrow or adipose. The present review discusses the phenotypic characteristics, therapeutic applications, and optimization of experimental protocols for WJ-derived stem cells. MSCs derived from WJ display promising transplantable features, including ease of sourcing, in vitro expandability, differentiation abilities, immune-evasion and immune-regulation capacities. Accumulating evidence demonstrates that WJ-derived stem cells possess many potential advantages as transplantable cells for treatment of various diseases (e.g., cancer, chronic liver disease, cardiovascular diseases, nerve, cartilage and tendon injury). Additional studies are warranted to translate the use of WJ-derived stem cells for clinical applications.
An ultrastructural quantitative assessment of hepatic stellate cells (HSCs) was made in relation ... more An ultrastructural quantitative assessment of hepatic stellate cells (HSCs) was made in relation to hepatic fibrosis, apoptotic cellular changes, intracellular fat deposition, circulating inflammatory cells in the sinusoids, and the necroinflammatory activity in liver specimens of 33 patients proven to be positive for hepatitis C virus (HCV)-RNA by polymerase chain reaction with the intention that electron microscopy may throw more light on the role of HSCs in the complicated process of fibrogenesis. A detailed review concerning these parameters and observed evidence suggesting the potential properties of HSCs to recycle cellular debris into collagen fibers are reported.
The in vivo angiogenic potential of transplanted human umbilical cord blood (UCB) CD133(+) stem c... more The in vivo angiogenic potential of transplanted human umbilical cord blood (UCB) CD133(+) stem cells in experimental chronic hepatic fibrosis induced by murine schistosomiasis was studied. Enriched cord blood-derived CD133(+) cells were cultured in primary medium for 3 weeks. Twenty-two weeks post-Schistosomiasis infection in mice, after reaching the chronic hepatic fibrotic stage, transplantation of stem cells was performed and mice were sacrificed 3 weeks later. Histopathology and electron microscopy showed an increase in newly formed blood vessels and a decrease in the fibrosis known for this stage of the disease. By immunohistochemical analysis the newly formed blood vessels showed positive expression of the human-specific angiogenic markers CD31, CD34 and von Willebrand factor. Few hepatocyte-like polygonal cells showed positive expression of human vascular endothelial growth factor and inducible nitric oxide synthase. The transplanted CD133(+) human stem cells primarily enhanced hepatic angiogenesis and neovascularization and contributed to repair in a paracrine manner by creating a permissive environment that enabled proliferation and survival of damaged cells rather than by direct differentiation to hepatocytes. A dual advantage of CD133(+) cell therapy in hepatic disease is suggested based on its capability of hematopoietic and endothelial differentiation.
Background Anthelminthic treatment options against schistosomiasis are limited. The current treat... more Background Anthelminthic treatment options against schistosomiasis are limited. The current treatment relies almost exclusively on a single drug, praziquantel (PZQ). As a consequence, the development of resistance to PZQ and limited activity of PZQ against earlier development stages are respectively a risk and a limitation to achieving the goals of the new WHO roadmap towards elimination. For the discovery of new chemical starting points, the in vitro drug screening on Schistosoma mansoni (S. mansoni) against newly transformed schistosomula (NTS) is still the most predominant approach. The use of only NTS in the initial screening limits sensitivity to potential new compounds which are predominantly active in later developmental stages. Using our recently described highly standardized, straightforward and reliable culture method that generates high rates of juvenile worms, we aimed to repurpose a subset of the National Center for Advancing Translational Sciences (NCATS) Pharmaceutica...
The efficiency of differentiation of bone marrow cells (BMCs) into hepatocytes in vivo and its im... more The efficiency of differentiation of bone marrow cells (BMCs) into hepatocytes in vivo and its importance in physiopathological processes is still debated. Murine schistosomiasis was used as a liver injury model and unfractionated male mice BMCs were transplanted through intrahepatic injection into non-irradiated Schistosoma mansoni-infected female mice on their 16th week post-infection. Two weeks after bone marrow transplantation, mice were sacrificed on a weekly basis until 10 weeks. Tracing of male donor-derived cells in female recipient mice livers was carried out by the detection of Y chromosome expression by fluorescent in situ hybridization (FISH) and also of chromodomain Y-linked (CDYL) protein by indirect immunofluorescence (IF). Their transformation into hepatocytes was studied by double labelling indirect IF using antibodies directed against CDYL and mouse albumin. Histopathological and electron microscopic examinations revealed the presence of small hepatocyte-like cells in the periportal tracts and in between the hepatocytes facing the sinusoids. Donor-derived cells showing Y chromosome by FISH and expressing CDYL protein by IF were recovered in the infected transplanted livers. The initial number of these cells increased with increased post-transplantation time. Cells were mainly localized in the periphery of schistosoma granuloma. Few donor-derived cells appeared within the hepatic parenchymal tissue and showed positivity for albumin secretion by double labelling with IF. We suggest that transplanted bone marrow stem cells can repopulate the Schistosoma-infected liver of immunocompetent mice. Their differentiation is a complex event controlled by many factors and needs to be further characterized extensively. The extent and type of liver injury and the number of transplanted cells are important variables in the process of stem cell engraftment and differentiation into functioning hepatic cells that still need to be defined.
Liver fibrosis is one of the most serious consequences of S. mansoni infection. The aim of the pr... more Liver fibrosis is one of the most serious consequences of S. mansoni infection. The aim of the present study was to investigate the potential anti-fibrotic effect of human Wharton’s jelly-derived mesenchymal stem cells (WJMSCs) combined with praziquantel (PZQ) in S. mansoni-infected mice. S. mansoni-infected mice received early (8th week post infection) and late (16th week post infection) treatment with WJMSCs, alone and combined with oral PZQ. At the 10th month post infection, livers were collected for subsequent flow cytometric, histopathological, morphometric, immunohistochemical, gene expression, and gelatin zymographic studies. After transplantation, WJMSCs differentiated into functioning liver-like cells as evidenced by their ability to express human hepatocyte-specific markers. Regression of S. mansoni-induced liver fibrosis was also observed in transplanted groups, as evidenced by histopathological, morphometric, and gelatin zymographic results besides decreased expression o...
One of the most serious consequences of Schistosoma ( S. ) mansoni infection is hepatic schistoso... more One of the most serious consequences of Schistosoma ( S. ) mansoni infection is hepatic schistosomiasis or periportal fibrosis. Treatment with praziquantel (PZQ) remains the mainstay of schistosomiasis control. Stem cells and their possible use in cell therapy have drawn much attention recently, due to their potential for self - renewal and differentiation. The present study aimed to investigate the ability of mesenchymal stem cells (MSCs) to integrate into the livers of S. mansoni - infected mice. S. mansoni - infected mice (60±10 cercariae/mouse, s.c.) received intra hepatic i njection of MSCs (1.5x10 6 cells/mouse), alone or combined with oral PZQ (500 mg/kg/day, for 2 days, seven weeks post infection). At the 10 th month post infection, flow cytometry and immunohistochemical analysis for human - specific β2 - globulin were performed . Immunohistochemical results showed positive hepatic expression for β2 - globulin. Interestingly, the integration of MSCs was found to be enhanced ...
ABSTRACT Wharton's jelly (WJ) is a gelatinous tissue within the umbilical cord that conta... more ABSTRACT Wharton's jelly (WJ) is a gelatinous tissue within the umbilical cord that contains myofibroblast-like stromal cells. A unique cell population of WJ that has been suggested as displaying the stemness phenotype is the mesenchymal stromal cells (MSCs). Because MSCs' stemness and immune properties appear to be more robustly expressed and functional which are more comparable with fetal than adult-derived MSCs, MSCs harvested from the "young" WJ are considered much more proliferative, immunosuppressive, and even therapeutically active stem cells than those isolated from older, adult tissue sources such as the bone marrow or adipose. The present review discusses the phenotypic characteristics, therapeutic applications, and optimization of experimental protocols for WJ-derived stem cells. MSCs derived from WJ display promising transplantable features, including ease of sourcing, in vitro expandability, differentiation abilities, immune-evasion and immune-regulation capacities. Accumulating evidence demonstrates that WJ-derived stem cells possess many potential advantages as transplantable cells for treatment of various diseases (e.g., cancer, chronic liver disease, cardiovascular diseases, nerve, cartilage and tendon injury). Additional studies are warranted to translate the use of WJ-derived stem cells for clinical applications.
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