scholarly journals Safety Evaluation of Human Cord-Lining Epithelial Stem Cells Transplantation for Liver Regeneration in a Porcine Model

2020 ◽  
Vol 29 ◽  
pp. 096368971989655
Author(s):  
Raymond Hon Giat Lim ◽  
Justin Xuan Kai Liew ◽  
Aileen Wee ◽  
Jeyakumar Masilamani ◽  
Stephen Kin Yong Chang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Epithelial Cells ◽  
Liver Regeneration ◽  
Porcine Model ◽  
Embryonic Stem ◽  
Large Animal ◽  
Epithelial Stem Cells ◽  
Produce Cell ◽  
Stem Cell Delivery ◽  
Promising Source

We investigated the safety of using umbilical cord-lining stem cells for liver regeneration and tested a novel method for stem cell delivery. Stem cells are known by their ability to repair damaged tissues and have the potential to be used as regenerative therapies. The umbilical cord’s outer lining membrane is known to be a promising source of multipotent stem cells and can be cultivated in an epithelial cell growth medium to produce cell populations which possess the properties of both epithelial cells and embryonic stem cells—termed cord-lining epithelial cells (CLEC). Hepatocytes are epithelial cells of the liver and their proliferation upon injury is the main mechanism in restoring the liver. Earlier studies conducted showed CLEC can be differentiated into functioning hepatocyte-like cells (HLC) and can survive in immunologically competent specimens. In this study, we chose a porcine model to investigate CLEC as a treatment modality for liver failure. We selected 16 immune competent Yorkshire-Dutch Landrace pigs, with a mean weight of 40.5 kg, for this study. We performed a 50% hepatectomy to simulate the liver insufficient disease model. After the surgery, four pigs were transplanted with a saline scaffold while seven pigs were transplanted with a HLC scaffold. Five pigs died on the surgical table and were omitted from the study analysis. This study addressed the safety of transplanting human CLEC in a large animal model. The transplant interfaces were evaluated and no signs of cellular rejection were observed in both groups.

386 HORSE AMNION: A SOURCE OF MESENCHYMAL (AMSC) AND EPITHELIAL STEM CELLS

2010 ◽  
Vol 22 (1) ◽  
pp. 349 ◽  
Author(s):  
A. Lange Consiglio ◽  
B. Corradetti ◽  
D. Bizzaro ◽  
M. Cassano ◽  
F. Cremonesi
Keyword(s):  
Stem Cells ◽  
Epithelial Cells ◽  
Amniotic Membrane ◽  
Embryonic Stem ◽  
Specific Pattern ◽  
Limiting Factor ◽  
Epithelial Stem Cells ◽  
Culture Dish ◽  
Isolated Cells ◽  
Differentiation Potential

According to the developmental stage from which they are obtained, stem cells are classified as being embryonic, fetal, or adult. Embryonic stem cells have unlimited self-renewing capacity and multilineage differentiation potential, but the separation of these cells requires destruction of the embryo. Moreover, their clinical application seems to be hindered by the high tumorigenic rate after transplantation. Stem cells derived from adult tissues are considered to be more limited in their potential; although, they are currently the more versatile cells in the clinical field. However, the risk of the immunological rejection of the transplanted stem cells by the recipient is an important limiting factor. In human medicine, stem cells isolated from term placenta are the ideal candidates for disease treatment, specifically because of their plasticity and reduced immunogenicity. The aim of this work was to provide, for the first time, an isolation protocol and the characteristics of the stem cells from horse amniotic membrane, which hold potential uses in equine clinical regenerative medicine. Minimal criteria for stemness definition are adherence to plastic culture dish, formation of fibroblast colony forming units (CFU-F), specific pattern of surface antigen expression, and differentiation potential toward one or more lineages. The amnion is a thin, avascular membrane composed of an epithelial layer and an outer layer of connective tissue. From 3 samples of allantoamnion retrieved at delivery, each amniotic membrane was stripped from the overlying allantois and, for isolation of the epithelial cells, digested with trypsin. After removal of epithelial cells, the AMSC population was obtained by digestion with collagenase and DNase. The cellular yield from term amnion was 10-fold more epithelial cells than AMSC. Isolated cells readily attached to plastic culture dishes. Culture was established in DMEM-HG medium, supplemented with 10% serum and EGF, where the cells proliferated robustly. Epithelial cells displayed typical cuboidal morphology, whereas AMSC were fibroblast-like. Normally, 5 to 6 passages were achieved before proliferation decreased, with a mean of 13.08 and 26.5 cell population doublings after 31 days, respectively, for epithelial cells and AMSC. The mean frequency of CFU-F was, respectively, 1 : 283 and 1:111 for epithelial cells and AMSC. The 2 cellular lines expressed MSC mRNA markers (CD29, CD105, CD44) and were negative for CD34, which was expressed at the fifth passage in both cellular types. Osteogenic differentiation of epithelial stem cells and AMSC was confirmed by von Kossa stain and by an increased expression of osteocalcin and osteopontin. Our preliminary data showed that equine amnion holds apparent potential as a source of presumptive stem cells, which might have widespread clinical applications, but aspects including immunohistochemical study, preclinical experimentation, and immunological properties must be studied.

scholarly journals Characteristics and Therapeutic Potential of Human Amnion-Derived Stem Cells

2021 ◽  
Vol 22 (2) ◽  
pp. 970
Author(s):  
Quan-Wen Liu ◽  
Qi-Ming Huang ◽  
Han-You Wu ◽  
Guo-Si-Lang Zuo ◽  
Hao-Cheng Gu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Cell Therapy ◽  
Adult Stem Cells ◽  
Therapeutic Potential ◽  
Embryonic Stem ◽  
Epithelial Stem Cells ◽  
Preclinical Research ◽  
Human Amnion ◽  
Promising Source

Stem cells including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and adult stem cells (ASCs) are able to repair/replace damaged or degenerative tissues and improve functional recovery in experimental model and clinical trials. However, there are still many limitations and unresolved problems regarding stem cell therapy in terms of ethical barriers, immune rejection, tumorigenicity, and cell sources. By reviewing recent literatures and our related works, human amnion-derived stem cells (hADSCs) including human amniotic mesenchymal stem cells (hAMSCs) and human amniotic epithelial stem cells (hAESCs) have shown considerable advantages over other stem cells. In this review, we first described the biological characteristics and advantages of hADSCs, especially for their high pluripotency and immunomodulatory effects. Then, we summarized the therapeutic applications and recent progresses of hADSCs in treating various diseases for preclinical research and clinical trials. In addition, the possible mechanisms and the challenges of hADSCs applications have been also discussed. Finally, we highlighted the properties of hADSCs as a promising source of stem cells for cell therapy and regenerative medicine and pointed out the perspectives for the directions of hADSCs applications clinically.

327 PORCINE AMNION: A SOURCE OF EPITHELIAL STEM CELLS

2015 ◽  
Vol 27 (1) ◽  
pp. 252 ◽  
Author(s):  
A. Lange-Consiglio ◽  
B. Corradetti ◽  
V. Notarstefano ◽  
M. G. Marini ◽  
C. Perrini ◽  
...  
Keyword(s):  
Stem Cells ◽  
Epithelial Cells ◽  
Amniotic Membrane ◽  
Adipogenic Differentiation ◽  
Embryonic Stem ◽  
Glial Fibrillary Acid Protein ◽  
Limiting Factor ◽  
Epithelial Stem Cells ◽  
Differentiation Potential ◽  
Stromal Layer

The use of pig models for preclinical testing is well established, and the availability of stem cells from this species would open the way to preclinical studies for application of cell therapy. According to the developmental stage from which they are obtained, stem cells are classified as being embryonic, fetal, or adult. Embryonic stem cells have unlimited self-renewing capacity and multilineage differentiation potential, but their clinical application seems to be hindered by the high tumorigenic rate after transplantation. Mesenchymal stem cells (MSC) derived from adult tissues are considered to be more limited in their potential and the risk of the immunological rejection of the transplanted stem cells by the recipient is an important limiting factor. The MSC derived from extra-fetal tissues could overcome many of these restrictions. Indeed, in veterinary medicine, MSC isolated from equine term placenta were the ideal candidates for tendon disease treatment, specifically for their plasticity and their reduced immunogenicity compared to bone marrow-derived cells. Extra-fetal derived MSC in porcine have been isolated from the umbilical cord matrix and amniotic fluid. The aim of this work was to provide, for the first time, an isolation protocol and the characterisation of stem cells from porcine amniotic membrane, which could hold potential uses in regenerative medicine. The amnion is a thin, avascular membrane made of an epithelial layer and an outer layer of connective tissue. From 3 samples of allanto-amnion retrieved at delivery, each amniotic membrane was stripped from the overlying allantois and, for isolation of the epithelial cells, it was digested with trypsin. After removal of epithelial cells, the stromal layer was digested with collagenase to obtain amniotic mesenchymal cells. The cellular yield from term amnion resulted only in epithelial cells (AEC) at a concentration of 10 × 106 for 1 g of digested tissue while no MSC were obtained. Histology, indeed, revealed very few cells in the stromal layer. The AEC readily attached to plastic culture dishes. Culture was established in DMEM-HG medium, supplemented with 10% serum and 10 ng mL–1 of EGF where the cells proliferated robustly. The AEC displayed typical cuboidal morphology. These cells showed a mean of 31 ± 0.24 cell population doublings after 31 days. The mean frequency of colony-forming unit fibroblasts was 1 for each of the 75 plated cells. The AEC expressed MSC mRNA markers (CD29, CD166, CD90, CD73, CD117) and pluripotent markers (Nanog and Oct4), while were negative for CD34 and MHC-II. Osteogenic, adipogenic, and neurogenic differentiations were confirmed by von Kossa, Red Oil, and Nissle stains, respectively, and by expression of specific markers (osteocalcin and osteopontin for osteogenic differentiation, adiponectin and leptin for adipogenic differentiation, and glial fibrillary acid protein and nestin for neurogenic differentiation). We conclude that porcine amnion contain unique and primitive cells whose potential is as yet undefined. Ease of collection and propagation of AEC make this tissue an attractive candidate as a resource for stem cell biotechnology and biomedical research.

scholarly journals Hair Follicle Dermal Cells Support Expansion of Murine and Human Embryonic and Induced Pluripotent Stem Cells and Promote Haematopoiesis in Mouse Cultures

2018 ◽  
Vol 2018 ◽  
pp. 1-14
Author(s):  
Jun Liu ◽  
Claire A. Higgins ◽  
Jenna C. Whitehouse ◽  
Susan J. Harris ◽  
Heather Crawford ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Hair Follicle ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Dermal Papilla ◽  
Epithelial Stem Cells ◽  
Stem Cell Maintenance ◽  
Induced Pluripotent ◽  
Dermal Cells

In the hair follicle, the dermal papilla (DP) and dermal sheath (DS) support and maintain proliferation and differentiation of the epithelial stem cells that produce the hair fibre. In view of their regulatory properties, in this study, we investigated the interaction between hair follicle dermal cells (DP and DS) and embryonic stem cells (ESCs); induced pluripotent stem cells (iPSCs); and haematopoietic stem cells. We found that coculture of follicular dermal cells with ESCs or iPSCs supported their prolonged maintenance in an apparently undifferentiated state as established by differentiation assays, immunocytochemistry, and RT-PCR for markers of undifferentiated ESCs. We further showed that cytokines that are involved in ESC support are also expressed by cultured follicle dermal cells, providing a possible explanation for maintenance of ES cell stemness in cocultures. The same cytokines were expressed within folliclesin situin a pattern more consistent with a role in follicle growth activities than stem cell maintenance. Finally, we show that cultured mouse follicle dermal cells provide good stromal support for haematopoiesis in an established coculture model. Human follicular dermal cells represent an accessible and readily propagated source of feeder cells for pluripotent and haematopoietic cells and have potential for use in clinical applications.

scholarly journals Terminal differentiation of ectodermal epithelial stem cells of Hydra can occur in G2 without requiring mitosis or S phase.

1990 ◽  
Vol 110 (4) ◽  
pp. 939-945 ◽  
Author(s):  
S Dübel ◽  
H C Schaller
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Epithelial Cells ◽  
Terminal Differentiation ◽  
S Phase ◽  
Epithelial Stem Cells ◽  
Proliferating Cells ◽  
Specific Differentiation ◽  
G2 Phase

Using bromodeoxyuridine incorporation to label cells in S phase we found that ectodermal epithelial cells of Hydra can start and complete their terminal differentiation in the G2 phase of the cell cycle. Most of the cells traversed their last S phase before the signal for differentiation, namely excision of head or foot, was given. The S phase inhibitor aphidicolin accordingly did not inhibit head or foot specific differentiation. The results show that differentiation to either head- or foot-specific ectodermal epithelial cells can start and is completed within the same G2 phase. This is therefore the first description of a complete differentiation from a population of proliferating cells to terminally differentiated, cell cycle-arrested cells without the necessity of passing through an S phase or mitosis.

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