scholarly journals Wound healing in the liver with particular reference to stem cells

1998 ◽  
Vol 353 (1370) ◽  
pp. 877-894 ◽  
Author(s):  
Malcolm Alison ◽  
Matthew Golding ◽  
El–Nasir Lalani ◽  
Catherine Sarraf
Keyword(s):  
Stem Cells ◽  
Ex Vivo ◽  
Biliary Tree ◽  
Target Population ◽  
Cell Types ◽  
Oval Cells ◽  
Inborn Errors ◽  
Ductal Cells ◽  
Biological Interest ◽  
A Cell

The efficiency of liver regeneration in response to the loss of hepatocytes is widely acknowledged, and this is usually accomplished by the triggering of normally proliferatively quiescent hepatocytes into the cell cycle. However, when regeneration is defective, tortuous ductular structures, initially continuous with the biliary tree, proliferate and migrate into the surrounding hepatocyte parenchyma. In humans, these biliary cells have variously been referred to as ductular structures, neoductules and neocholangioles, and have been observed in many forms of chronic liver disease, including cancer. In experimental animals, similar ductal cells are usually called oval cells, and their association with impaired regeneration has led to the conclusion that they are the progeny of facultative stem cells. Oval cells are of considerable biological interest as they may represent a target population for hepatic carcinogens, and they may also be useful vehicles for ex vivo gene therapy for the correction of inborn errors of metabolism. This review proposes that the liver harbours stem cells that are located in the biliary epithelium, that oval cells are the progeny of these stem cells, and that these cells can undergo massive expansion in their numbers before differentiating into hepatocytes. This is a conditional process that only occurs when the regenerative capacity of hepatocytes is overwhelmed, and thus, unlike the intestinal epithelium, the liver is not behaving as a classical, continually renewing, stem cell–fed lineage. We focus on the biliary network, not merely as a conduit for bile, but also as a cell compartment with the ability to proliferate under appropriate conditions and give rise to fully differentiated hepatocytes and other cell types.

scholarly journals Capacity for stochastic self-renewal and differentiation in mammalian spermatogonial stem cells

2009 ◽  
Vol 187 (4) ◽  
pp. 513-524 ◽  
Author(s):  
Zhuoru Wu ◽  
Katherine Luby-Phelps ◽  
Abhijit Bugde ◽  
Laura A. Molyneux ◽  
Bray Denard ◽  
...  
Keyword(s):  
Stem Cells ◽  
Ex Vivo ◽  
Cell Types ◽  
Spermatogonial Stem Cells ◽  
Culture Conditions ◽  
Basic Question ◽  
Self Renewal ◽  
A Cell ◽  
Fate Decision ◽  
Ex Vivo Culture

Mammalian spermatogenesis is initiated and sustained by spermatogonial stem cells (SSCs) through self-renewal and differentiation. The basic question of whether SSCs have the potential to specify self-renewal and differentiation in a cell-autonomous manner has yet to be addressed. Here, we show that rat SSCs in ex vivo culture conditions consistently give rise to two distinct types of progeny: new SSCs and differentiating germ cells, even when they have been exposed to virtually identical microenvironments. Quantitative experimental measurements and mathematical modeling indicates that fate decision is stochastic, with constant probability. These results reveal an unexpected ability in a mammalian SSC to specify both self-renewal and differentiation through a self-directed mechanism, and further suggest that this mechanism operates according to stochastic principles. These findings provide an experimental basis for autonomous and stochastic fate choice as an alternative strategy for SSC fate bifurcation, which may also be relevant to other stem cell types.

scholarly journals The interplay of osteogenesis and hematopoiesis

2004 ◽  
Vol 167 (6) ◽  
pp. 1113-1122 ◽  
Author(s):  
Sergei A. Kuznetsov ◽  
Mara Riminucci ◽  
Navid Ziran ◽  
Takeo W. Tsutsui ◽  
Alessandro Corsi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Parathyroid Hormone ◽  
Ex Vivo ◽  
Cell Types ◽  
Heterotopic Bone ◽  
Stromal Compartment ◽  
Marrow Space ◽  
Stromal Tissue

The ontogeny of bone marrow and its stromal compartment, which is generated from skeletal stem/progenitor cells, was investigated in vivo and ex vivo in mice expressing constitutively active parathyroid hormone/parathyroid hormone–related peptide receptor (PTH/PTHrP; caPPR) under the control of the 2.3-kb bone-specific mouse Col1A1 promoter/enhancer. The transgene promoted increased bone formation within prospective marrow space, but delayed the transition from bone to bone marrow during growth, the formation of marrow cavities, and the appearance of stromal cell types such as marrow adipocytes and cells supporting hematopoiesis. This phenotype resolved spontaneously over time, leading to the establishment of marrow containing a greatly reduced number of clonogenic stromal cells. Proliferative osteoprogenitors, but not multipotent skeletal stem cells (mesenchymal stem cells), capable of generating a complete heterotopic bone organ upon in vivo transplantation were assayable in the bone marrow of caPPR mice. Thus, PTH/PTHrP signaling is a major regulator of the ontogeny of the bone marrow and its stromal tissue, and of the skeletal stem cell compartment.

scholarly journals Bile Acids Activate NLRP3 Inflammasome, Promoting Murine Liver Inflammation or Fibrosis in a Cell Type-Specific Manner

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2618
Author(s):  
Theresa Maria Holtmann ◽  
Maria Eugenia Inzaugarat ◽  
Jana Knorr ◽  
Lukas Geisler ◽  
Marten Schulz ◽  
...  
Keyword(s):  
Bile Acids ◽  
Liver Damage ◽  
Nlrp3 Inflammasome ◽  
Lithocholic Acid ◽  
Ex Vivo ◽  
Cell Types ◽  
Inflammasome Activation ◽  
Inflammatory Phenotype ◽  
Murine Liver ◽  
A Cell

Bile acids (BA) as important signaling molecules are considered crucial in development of cholestatic liver injury, but there is limited understanding on the involved cell types and signaling pathways. The aim of this study was to evaluate the inflammatory and fibrotic potential of key BA and the role of distinct liver cell subsets focusing on the NLRP3 inflammasome. C57BL/6 wild-type (WT) and Nlrp3−/− mice were fed with a diet supplemented with cholic (CA), deoxycholic (DCA) or lithocholic acid (LCA) for 7 days. Additionally, primary hepatocytes, Kupffer cells (KC) and hepatic stellate cells (HSC) from WT and Nlrp3−/− mice were stimulated with aforementioned BA ex vivo. LCA feeding led to strong liver damage and activation of NLRP3 inflammasome. Ex vivo KC were the most affected cells by LCA, resulting in a pro-inflammatory phenotype. Liver damage and primary KC activation was both ameliorated in Nlrp3-deficient mice or cells. DCA feeding induced fibrotic alterations. Primary HSC upregulated the NLRP3 inflammasome and early fibrotic markers when stimulated with DCA, but not LCA. Pro-fibrogenic signals in liver and primary HSC were attenuated in Nlrp3−/− mice or cells. The data shows that distinct BA induce NLRP3 inflammasome activation in HSC or KC, promoting fibrosis or inflammation.

scholarly journals Do Neural Stem Cells Have a Choice? Heterogenic Outcome of Cell Fate Acquisition in Different Injury Models

2019 ◽  
Vol 20 (2) ◽  
pp. 455 ◽  
Author(s):  
Felix Beyer ◽  
Iria Samper Agrelo ◽  
Patrick Küry
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Ex Vivo ◽  
Meta Analysis ◽  
Cell Types ◽  
Adult Brain ◽  
Repair Capacity ◽  
Cell Fate Decisions ◽  
Limiting Parameters

The adult mammalian central nervous system (CNS) is generally considered as repair restricted organ with limited capacities to regenerate lost cells and to successfully integrate them into damaged nerve tracts. Despite the presence of endogenous immature cell types that can be activated upon injury or in disease cell replacement generally remains insufficient, undirected, or lost cell types are not properly generated. This limitation also accounts for the myelin repair capacity that still constitutes the default regenerative activity at least in inflammatory demyelinating conditions. Ever since the discovery of endogenous neural stem cells (NSCs) residing within specific niches of the adult brain, as well as the description of procedures to either isolate and propagate or artificially induce NSCs from various origins ex vivo, the field has been rejuvenated. Various sources of NSCs have been investigated and applied in current neuropathological paradigms aiming at the replacement of lost cells and the restoration of functionality based on successful integration. Whereas directing and supporting stem cells residing in brain niches constitutes one possible approach many investigations addressed their potential upon transplantation. Given the heterogeneity of these studies related to the nature of grafted cells, the local CNS environment, and applied implantation procedures we here set out to review and compare their applied protocols in order to evaluate rate-limiting parameters. Based on our compilation, we conclude that in healthy CNS tissue region specific cues dominate cell fate decisions. However, although increasing evidence points to the capacity of transplanted NSCs to reflect the regenerative need of an injury environment, a still heterogenic picture emerges when analyzing transplantation outcomes in injury or disease models. These are likely due to methodological differences despite preserved injury environments. Based on this meta-analysis, we suggest future NSC transplantation experiments to be conducted in a more comparable way to previous studies and that subsequent analyses must emphasize regional heterogeneity such as accounting for differences in gray versus white matter.

Human hematopoietic stem cells stimulated to proliferate in vitro lose engraftment potential during their S/G2/M transit and do not reenter G0

Blood ◽  
2000 ◽  
Vol 96 (13) ◽  
pp. 4185-4193 ◽  
Author(s):  
Hanno Glimm ◽  
IL-Hoan Oh ◽  
Connie J. Eaves
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Transforming Growth Factor ◽  
Ex Vivo ◽  
Cell Activity ◽  
Human Cord Blood ◽  
Hematopoietic Stem ◽  
A Cell

Abstract An understanding of mechanisms regulating hematopoietic stem cell engraftment is of pivotal importance to the clinical use of cultured and genetically modified transplants. Human cord blood (CB) cells with lymphomyeloid repopulating activity in NOD/SCID mice were recently shown to undergo multiple self-renewal divisions within 6 days in serum-free cultures containing Flt3-ligand, Steel factor, interleukin 3 (IL-3), IL-6, and granulocyte colony-stimulating factor. The present study shows that, on the fifth day, the transplantable stem cell activity is restricted to the G1fraction, even though both colony-forming cells (CFCs) and long-term culture-initiating cells (LTC-ICs) in the same cultures are approximately equally distributed between G0/G1and S/G2/M. Interestingly, the G0 cells defined by their low levels of Hoechst 33342 and Pyronin Y staining, and reduced Ki67 and cyclin D expression (representing 21% of the cultured CB population) include some mature erythroid CFCs but very few primitive CFCs, LTC-ICs, or repopulating cells. Although these findings suggest a cell cycle–associated change in in vivo stem cell homing, the cultured G0/G1 and S/G2/M CD34+ CB cells exhibited no differences in levels of expression of VLA-4, VLA-5, or CXCR-4. Moreover, further incubation of these cells for 1 day in the presence of a concentration of transforming growth factor β1 that increased the G0/G1 fraction did not enhance detection of repopulating cells. The demonstration of a cell cycle–associated mechanism that selectively silences the transplantability of proliferating human hematopoietic stem cells poses both challenges and opportunities for the future improvement of ex vivo–manipulated grafts.

Transdifferentiation of pancreatic ductal cells to endocrine β-cells

2008 ◽  
Vol 36 (3) ◽  
pp. 353-356 ◽  
Author(s):  
Susan Bonner-Weir ◽  
Akari Inada ◽  
Shigeru Yatoh ◽  
Wan-Chun Li ◽  
Tandy Aye ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Duct Cell ◽  
Cell Types ◽  
Lineage Tracing ◽  
Β Cells ◽  
Partial Pancreatectomy ◽  
Pancreatic Cell ◽  
Ductal Cells ◽  
Pancreatic Ductal Cells

The regenerative process in the pancreas is of particular interest, since diabetes, whether Type 1 or Type 2, results from an inadequate amount of insulin-producing β-cells. Islet neogenesis, or the formation of new islets, seen as budding of hormone-positive cells from the ductal epithelium, has long been considered to be one of the mechanisms of normal islet growth after birth and in regeneration, and suggested the presence of pancreatic stem cells. Results from the rat regeneration model of partial pancreatectomy led us to hypothesize that differentiated pancreatic ductal cells were the pancreatic progenitors after birth, and that with replication they regressed to a less differentiated phenotype and then could differentiate to form new acini and islets. There are numerous supportive results for this hypothesis of neogenesis, including the ability of purified primary human ducts to form insulin-positive cells budding from ducts. However, to rigorously test this hypothesis, we took a direct approach of genetically marking ductal cells using CAII (carbonic anhydrase II) as a duct-cell-specific promoter to drive Cre recombinase in lineage-tracing experiments using the Cre-Lox system. We show that CAII-expressing pancreatic cells act as progenitors that give rise to both new islets and acini after birth and after injury (ductal ligation). This identification of a differentiated pancreatic cell type as an in vivo progenitor for all differentiated pancreatic cell types has implications for a potential expandable source for new islets for replenishment therapy for diabetes either in vivo or ex vivo.

scholarly journals Human Mesenchymal Stem Cells Display Reduced Expression of CD105 after Culture in Serum-Free Medium

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Peter Mark ◽  
Mandy Kleinsorge ◽  
Ralf Gaebel ◽  
Cornelia A. Lux ◽  
Anita Toelk ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ex Vivo ◽  
Human Mesenchymal Stem Cells ◽  
Cell Types ◽  
Growth Media ◽  
Clinical Use ◽  
Differentiation Potential ◽  
Serum Free ◽  
The Impact

Human Mesenchymal Stem Cells (hMSCs) present a promising tool for regenerative medicine. However,ex vivoexpansion is necessary to obtain sufficient cells for clinical therapy. Conventional growth media usually contain the critical component fetal bovine serum. For clinical use, chemically defined media will be required. In this study, the capability of two commercial, chemically defined, serum-free hMSC growth media (MSCGM-CD and PowerStem) for hMSC proliferation was examined and compared to serum-containing medium (MSCGM). Immunophenotyping of hMSCs was performed using flow cytometry, and they were tested for their ability to differentiate into a variety of cell types. Although the morphology of hMSCs cultured in the different media differed, immunophenotyping displayed similar marker patterns (high expression of CD29, CD44, CD73, and CD90 cell surface markers and absence of CD45). Interestingly, the expression of CD105 was significantly lower for hMSCs cultured in MSCGM-CD compared to MSCGM. Both groups maintained mesenchymal multilineage differentiation potential. In conclusion, the serum-free growth medium is suitable for hMSC culture and comparable to its serum-containing counterpart. As the expression of CD105 has been shown to positively influence hMSC cardiac regenerative potential, the impact of CD105 expression onto clinical use after expansion in MSCGM-CD will have to be tested.

Recreating a Human Hematopoietic Stem Cell Niche in Vitro by Unique Stroma Cells from the First Trimester Human Placenta and Fetal Liver

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3568-3568
Author(s):  
Mattias Magnusson ◽  
Melissa Romero ◽  
Sacha Prashad ◽  
Ben Van Handel ◽  
Suvi Aivio ◽  
...  
Keyword(s):  
Stem Cells ◽  
Human Placenta ◽  
Ex Vivo ◽  
Fetal Liver ◽  
Embryonic Stem ◽  
Cell Types ◽  
First Trimester ◽  
Hematopoietic Stem ◽  
Human Hscs

Abstract Expansion of human hematopoietic stem cells (HSCs) ex vivo has been difficult due to limited understanding of their growth requirements and the molecular complexity of their natural microenvironments. To mimic the niches in which human HSCs normally develop and expand during ontogeny, we have derived two unique types of stromal niche cells from the first trimester human placenta and the fetal liver. These lines either support maintenance of multipotential progenitors in culture, or promote differentiation into macrophages. Impressively, the supportive lines facilitate over 50,000-fold expansion of the most immature human HSCs/progenitors (CD34+CD38-Thy1+) during 8-week culture supplemented with minimal cytokines FLT3L, SCF and TPO, whereas the cells cultured on non-supportive stroma or without stroma under the same conditions differentiated within 2 weeks. As the supportive stroma lines also facilitate differentiation of human hematopoietic progenitors into myeloid, erythroid and B-lymphoid lineages, we were able to show that the expanded progenitors preserved full multipotentiality during long-term culture ex vivo. Furthermore, our findings indicate that the supportive stroma lines also direct differentiation of human embryonic stem cells (hESC) into hematopoietic progenitor cells (CD45+CD34+) that generate multiple types of myeloerythroid colonies. These data imply that the unique supportive niche cells can both support hematopoietic specification and sustain a multilineage hematopoietic hierarchy in culture over several weeks. Strikingly, the supportive effect from the unique stromal cells was dominant over the differentiation effect from the non-supportive lines. Even supernatant from the supportive lines was able to partially protect the progenitors that were cultured on the non-supportive lines, whereas mixing of the two types of stroma resulted in sustained preservation of the multipotential progenitors. These results indicate that the supportive stroma cells possess both secreted and surface bound molecules that protect multipotentiality of HSCs. Global gene expression analysis revealed that the supportive stroma lines from both the placenta and the fetal liver were almost identical (r=0.99) and very different from the non-supportive lines that promote differentiation (r=0.34), implying that they represent two distinct niche cell types. Interestingly, the non-supportive lines express known mesenchymal markers such as (CD73, CD44 and CD166), whereas the identity of the supportive cells is less obvious. In summary, we have identified unique human stromal niche cells that may be critical components of the HSC niches in the placenta and the fetal liver. Molecular characterization of these stroma lines may enable us to define key mechanisms that govern the multipotentiality of HSCs.

Human hematopoietic stem cells stimulated to proliferate in vitro lose engraftment potential during their S/G2/M transit and do not reenter G0

Blood ◽  
2000 ◽  
Vol 96 (13) ◽  
pp. 4185-4193 ◽  
Author(s):  
Hanno Glimm ◽  
IL-Hoan Oh ◽  
Connie J. Eaves
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Transforming Growth Factor ◽  
Ex Vivo ◽  
Cell Activity ◽  
Human Cord Blood ◽  
Hematopoietic Stem ◽  
A Cell

An understanding of mechanisms regulating hematopoietic stem cell engraftment is of pivotal importance to the clinical use of cultured and genetically modified transplants. Human cord blood (CB) cells with lymphomyeloid repopulating activity in NOD/SCID mice were recently shown to undergo multiple self-renewal divisions within 6 days in serum-free cultures containing Flt3-ligand, Steel factor, interleukin 3 (IL-3), IL-6, and granulocyte colony-stimulating factor. The present study shows that, on the fifth day, the transplantable stem cell activity is restricted to the G1fraction, even though both colony-forming cells (CFCs) and long-term culture-initiating cells (LTC-ICs) in the same cultures are approximately equally distributed between G0/G1and S/G2/M. Interestingly, the G0 cells defined by their low levels of Hoechst 33342 and Pyronin Y staining, and reduced Ki67 and cyclin D expression (representing 21% of the cultured CB population) include some mature erythroid CFCs but very few primitive CFCs, LTC-ICs, or repopulating cells. Although these findings suggest a cell cycle–associated change in in vivo stem cell homing, the cultured G0/G1 and S/G2/M CD34+ CB cells exhibited no differences in levels of expression of VLA-4, VLA-5, or CXCR-4. Moreover, further incubation of these cells for 1 day in the presence of a concentration of transforming growth factor β1 that increased the G0/G1 fraction did not enhance detection of repopulating cells. The demonstration of a cell cycle–associated mechanism that selectively silences the transplantability of proliferating human hematopoietic stem cells poses both challenges and opportunities for the future improvement of ex vivo–manipulated grafts.

Intercelular adhesion of teratocarcinoma STEM cells

1983 ◽  
Vol 41 ◽  
pp. 580-583
Author(s):  
L. B. Grabel ◽  
G. R. Martin ◽  
S. D. Rosen
Keyword(s):  
Stem Cells ◽  
Cell Surface ◽  
Molecular System ◽  
Divalent Cations ◽  
Cell Types ◽  
Recognition System ◽  
Intercellular Adhesion ◽  
Cell Type ◽  
Multiple Systems ◽  
A Cell

A major research interest is the identification of the cell surface molecules responsible for the selective intercellular adhesion of various cell types. Initially it was believed that cell-cell adhesion was mediated by tissue specific lock and key molecules present on adjacent cells; a single molecular recognition system would be sufficient to generate the desired selectivity. In the past few years it has become apparent that although specific recognition molecules are certainly involved in mediating intercellular adhesion, the idea of each cell type having a single unique molecular system of recognition is an oversimplification. The available data suggest that multiple systems of adhesion function simultaneously in any given cell type, and that the same or similar molecules may be involved in adhesion within different tissues.We have been studying the intercellular adhesion of teratocarcinoma stem cells, and review here evidence that at least two separable components are involved in their intercellular adhesion; one requiring the presence of divalent cations, and the other one involving recognition by a cell surface fucan/mannan specific lectin.

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