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Bhardwaj G, Vakani M, Srivastava A, Rawal K, Kalathil A, Gupta S. Influence of metabolically compromised Adipose derived stem cell secretome on islet differentiation and functionality. Exp Cell Res 2022; 410:112970. [PMID: 34896076 DOI: 10.1016/j.yexcr.2021.112970] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 12/06/2021] [Accepted: 12/08/2021] [Indexed: 01/07/2023]
Abstract
Islet integrity plays a major role in maintaining glucose homeostasis and thus replenishment of damaged islets by differentiation of resident endocrine progenitors into neo islets regulates the islet functionality. Islet differentiation is affected by many factors including crosstalk with various organs by secretome. Adipose derived stem cells (ADSC) secrete a large array of factors in the extracellular milieu that exhibit regulatory effects on other tissues including pancreatic islets. The microenvironment of metabolically compromised human ADSCs (hADSCs) has a detrimental impact on islet functionality. In the present study, the role of secretome was studied on the differentiation of islets. Expression of key transcription factors like HNF-3B, NGN-3, NeuroD, PDX- 1, Maf-A, and GLUT-2 involved in development were differentially regulated in obese hADSC secretome as compared to control hADSC secretome. Islet like cell clusters (ILCCs) functionality and viability were critically hampered under obese hADSC secretome with compromised yield, morphometry, lower expression of C-peptide and Glucagon as well as higher ROS activity and cell death parameters. This study provides considerable insights on two major findings which are (i) exploring the use of hADSC secretome in islet differentiation and (ii) understanding the regulating effect of altered hADSC secretome under a metabolically compromised condition.
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Affiliation(s)
- Gurprit Bhardwaj
- Molecular Endocrinology and Stem Cell Research Laboratory, Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, 390021, India.
| | - Mitul Vakani
- Molecular Endocrinology and Stem Cell Research Laboratory, Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, 390021, India
| | - Abhay Srivastava
- Regenerative Medicine Program, Institute of Cardiovascular Sciences, Department of Physiology and Pathophysiology, St. Boniface Hospital Albrechtsen Research Centre, University of Manitoba, Winnipeg, MB, Canada
| | - Komal Rawal
- Molecular Endocrinology and Stem Cell Research Laboratory, Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, 390021, India
| | - Amrita Kalathil
- Molecular Endocrinology and Stem Cell Research Laboratory, Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, 390021, India
| | - Sarita Gupta
- Molecular Endocrinology and Stem Cell Research Laboratory, Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, 390021, India.
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Reversible immortalization of Nestin-positive precursor cells from pancreas and differentiation into insulin-secreting cells. Biochem Biophys Res Commun 2012; 418:330-5. [PMID: 22266322 DOI: 10.1016/j.bbrc.2012.01.021] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2011] [Accepted: 01/06/2012] [Indexed: 12/18/2022]
Abstract
Pancreatic stem cells or progenitor cells posses the ability of directed differentiation into pancreatic β cells. However, these cells usually have limited proliferative capacity and finite lifespan in vitro. In the present study, Nestin-positive progenitor cells (NPPCs) from mouse pancreas that expressed the pancreatic stem cells or progenitor cell marker Nestin were isolated to obtain a sufficient number of differentiated pancreatic β cells. Tet-on system for SV40 large T-antigen expression in NPPCs was used to achieve reversible immortalization. The reversible immortal Nestin-positive progenitor cells (RINPPCs) can undergo at least 80 population doublings without senescence in vitro while maintaining their biological and genetic characteristics. RINPPCs can be efficiently induced to differentiate into insulin-producing cells that contain a combination of glucagon-like peptide-1 (GLP-1) and sodium butyrate. The results of the present study can be used to explore transplantation therapy of type I diabetes mellitus.
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Venkatesan V, Gopurappilly R, Goteti SK, Dorisetty RK, Bhonde RR. Pancreatic progenitors: The shortest route to restore islet cell mass. Islets 2011; 3:295-301. [PMID: 21934353 DOI: 10.4161/isl.3.6.17704] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
The regenerative process of the pancreas is of interest because the main pathogenesis of diabetes mellitus is an inadequate number of insulin-producing β-cells. The functional mass of β-cells is decreased in most forms of diabetes, so replacing missing β-cells or triggering their regeneration may allow for improved diabetes treatment. Therefore, expansion of the β-cell mass from endogenous sources, either in vivo or in vitro, represents an area of increasing interest. The mechanism of islet regeneration remains poorly understood, but the identification of islet progenitor sources is critical for understanding β-cell regeneration. One potential source is the islet proper, via the de-differentiation, proliferation and redifferentiation of facultative progenitors residing within the islet. The new pancreatic islets derived from progenitor cells present within the ducts have been reported, but the existence and identity of the progenitor cells have been debated. In this mini-review, we focus primarily on pancreatic progenitors, which are islet progenitors capable of differentiating into insulin producing cells. We also emphasize the importance of pancreatic progenitors as a target for stem cell therapy for diabetes.
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Affiliation(s)
- Vijayalakshmi Venkatesan
- Department of Biochemistry/Stem Cell Research, National Institute of Nutrition, Hyderabad, India.
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Zhang Y, Shen W, Hua J, Lei A, Lv C, Wang H, Yang C, Gao Z, Dou Z. Pancreatic islet-like clusters from bone marrow mesenchymal stem cells of human first-trimester abortus can cure streptozocin-induced mouse diabetes. Rejuvenation Res 2011; 13:695-706. [PMID: 21204652 DOI: 10.1089/rej.2009.1016] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Bone marrow mesenchymal stem cells (BMSCs) have been reported to possess low immunogenicity and cause immunosuppression of recipients when allografted. They can differentiate into insulin-producing cells and may be a valuable source for islet formation. However, the extremely low differentiating rate of adult BMSCs toward insulin-producing cells and the insufficient insulin secretion of the differentiated BMSCs in vitro prevent their clinical use in diabetes treatment. Little is known about the potential of cell replacement therapy with human BMSCs. Previously, we isolated and identified human first-trimester fetal BMSCs (hfBMSCs). Under a novel four-step induction procedure established in this study, the hfBMSCs effectively differentiated into functional pancreatic islet-like cell clusters that contained 62 ± 14% insulin-producing cells, expressed a broad gene profile related to pancreatic islet β-cell development, and released high levels of insulin (2.245 ± 0.222 pmol/100 clusters per 30 min) and C-peptide (2.200 ± 0.468 pmol/100 clusters per 30 min) in response to 25 mmol/L glucose stimulus in vitro. The pancreatic islet-like cell clusters normalized the blood glucose level of diabetic model mice for at least 9 weeks when xenografted; blood glucose levels in these mice rose abnormally again when the grafts were removed. Examination of the grafts indicated that the transplanted cells survived in recipients and produced human insulin and C-peptide in situ. These results demonstrate that hfBMSCs derived from a human first-trimester abortus can differentiate into pancreatic islet-like cell clusters following an established four-step induction. The insulin-producing clusters present advantages in cell replacement therapy of type 1 diabetic model mice.
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Affiliation(s)
- Yihua Zhang
- Shaanxi Branch of National Stem Cell Engineering and Technology Centre, College of Veterinary Medicine, Northwest A & F University, Yangling, Shaanxi, China
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Dorisetty RK, Kiran SG, Umrani MR, Boindala S, Bhonde RR, Venkatesan V. Immunolocalization of nestin in pancreatic tissue of mice at different ages. World J Gastroenterol 2008; 14:7112-6. [PMID: 19084919 PMCID: PMC2776842 DOI: 10.3748/wjg.14.7112] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To localize nestin positive cells (NPC) in pancreatic tissue of mice of different ages.
METHODS: Paraffin sections of 6-8 μm of fixed pancreatic samples were mounted on poly-L-lysine coated slides and used for Immunolocalization using appropriate primary antibodies (Nestin, Insulin, Glucagon), followed by addition of a fluorescently labeled secondary antibody. The antigen-antibody localization was captured using a confocal microscope (Leica SP 5 series).
RESULTS: In 3-6 d pups, the NPC were localized towards the periphery of the endocrine portion, as evident from immunolocalization of insulin and glucagon, while NPC were absent in the acinar portion. At 2 wk, NPC were localized in both the exocrine and endocrine portions. Interestingly, in 4-wk-old mice NPC were seen only in the endocrine portion, towards the periphery, and were colocalized with the glucagon positive cells. In the pancreas of 8- wk-old mice, the NPC were predominantly localized in the central region of the islet clusters, where immunostaining for insulin was at a maximum.
CONCLUSION: We report for the first time the immunolocalization of NPC in the pancreas of mice of different ages (3 d to 8 wk) with reference to insulin and glucagon positive cells. The heterogeneous localization of the NPC observed may be of functional and developmental significance and suggest(s) that mice pancreatic tissue can be a potential source of progenitor cells. NPC from the pancreas can be isolated, proliferated and programmed to differentiate into insulin secreting cells under the appropriate microenvironment.
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Combination of GLP-1 and sodium butyrate promote differentiation of pancreatic progenitor cells into insulin-producing cells. Tissue Cell 2008; 40:437-45. [DOI: 10.1016/j.tice.2008.04.006] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2008] [Revised: 04/17/2008] [Accepted: 04/23/2008] [Indexed: 12/27/2022]
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Sordi V, Bertuzzi F, Piemonti L. Diabetes mellitus: an opportunity for therapy with stem cells? Regen Med 2008; 3:377-97. [PMID: 18462060 DOI: 10.2217/17460751.3.3.377] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
In both Type 1 and 2 diabetes, insufficient numbers of insulin-producing beta-cells are a major cause of defective control of blood glucose and its complications. Restoration of damaged beta-cells by endocrine pancreas regeneration would be an ideal therapeutic option. The possibility of generating insulin-secreting cells with adult pancreatic stem or progenitor cells has been investigated extensively. The conversion of differentiated cells such as hepatocytes into beta-cells is being attempted using molecular insights into the transcriptional make-up of beta-cells. Additionally, the enhanced proliferation of beta-cells in vivo or in vitro is being pursued as a strategy for regenerative medicine for diabetes. Advances have also been made in directing the differentiation of embryonic stem cells into beta-cells. Although progress is encouraging, major gaps in our understanding of developmental biology of the pancreas and adult beta-cell dynamics remain to be bridged before a therapeutic application is made possible.
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Affiliation(s)
- Valeria Sordi
- Laboratory of Experimental Surgery, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy
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Salehi F, Kovacs K, Cusimano MD, Horvath E, Bell CD, Rotondo F, Scheithauer BW. Immunohistochemical expression of nestin in adenohypophysial vessels during development of pituitary infarction. J Neurosurg 2008; 108:118-23. [PMID: 18173320 DOI: 10.3171/jns/2008/108/01/0118] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The aim of this work was to investigate the immunohistochemical expression of nestin, a member of the intermediate filament family, in adenohypophysial vasculature during development and progression of pituitary infarction. METHODS Forty-five nontumorous adenohypophyses and 34 pituitary adenomas of various types, all exhibiting acute or healing infarcts, were examined immunohistochemically using the streptavidin-biotin-peroxidase complex method. RESULTS In both adenohypophyses and pituitary adenomas without infarction, nestin was expressed in only a few capillaries and endothelial cells. In acute infarcts without a vascular response, no nestin was demonstrable within necrotic capillaries (50 cases). In organizing infarcts, newly formed vessels spreading into necrotic zones showed nestin expression in all capillaries and practically every endothelial cell (25 cases). In the hypocellular, fibrotic scar phase, only a few vessels (4) were apparent, and immunoreactivity was focal and mild. CONCLUSIONS Nestin is strongly expressed in newly formed capillaries and is downregulated when infarcts transform to fibrous tissue. Nestin expression may provide valuable insight into the process of pituitary angiogenesis.
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Affiliation(s)
- Fateme Salehi
- Department of Laboratory Medicine, St. Michael's Hospital, University of Toronto, Ontario, Canada
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PDZ-domain containing-2 (PDZD2) is a novel factor that affects the growth and differentiation of human fetal pancreatic progenitor cells. Int J Biochem Cell Biol 2008; 40:789-803. [DOI: 10.1016/j.biocel.2007.10.020] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2007] [Revised: 10/12/2007] [Accepted: 10/17/2007] [Indexed: 01/29/2023]
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Lü P, Liu F, Yan L, Peng T, Liu T, Yao Z, Wang CY. Stem cells therapy for type 1 diabetes. Diabetes Res Clin Pract 2007; 78:1-7. [PMID: 17349714 DOI: 10.1016/j.diabres.2007.02.003] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2006] [Revised: 01/10/2007] [Accepted: 02/02/2007] [Indexed: 11/30/2022]
Abstract
In this article, we have reviewed the developments of studies of stem cells therapy for type 1 diabetes since this century. Review of the literature was based on computer searches (PubMed) and our studies. Type 1 diabetes can now be ameliorated by islet transplantation, but this treatment is restricted by the scarcity of islet tissue. Hopes for a limitless supply of a substitute for primary islets of Langerhans and progress in stem cell biology have led to research into the feasibility of stem/progenitor cells to generate insulin-producing cells to use in replacement therapies for diabetes. An increasing body of evidence indicated that, in addition to embryonic stem cells, several potential adult stem/progenitor cells, derived from pancreas, liver, spleen, and bone marrow could differentiate into insulin-producing cells in vitro or in vivo. However, significant controversy currently exists in this field. Moreover, safe suppression of autoimmunity or specific tolerance to auto-antigens for patients with type 1 diabetes must be achieved before this promising new technology can lead to a great progress in clinical practice. To prevent type 1 diabetes through genetic engineering of hematopoietic stem cells represents another new strategy. Much basic research is still required.
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Affiliation(s)
- Ping Lü
- Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.
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11
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Shim JH, Kim SE, Woo DH, Kim SK, Oh CH, McKay R, Kim JH. Directed differentiation of human embryonic stem cells towards a pancreatic cell fate. Diabetologia 2007; 50:1228-38. [PMID: 17457565 DOI: 10.1007/s00125-007-0634-z] [Citation(s) in RCA: 168] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2006] [Accepted: 01/15/2007] [Indexed: 12/13/2022]
Abstract
AIMS/HYPOTHESIS The relative lack of successful pancreatic differentiation of human embryonic stem cells (hESCs) may suggest that directed differentiation of hESCs into definitive endoderm and subsequent commitment towards a pancreatic fate are not readily achieved. The aim of this study was to investigate whether sequential exposure of hESCs to epigenetic signals that mimic in vivo pancreatic development can efficiently generate pancreatic endodermal cells, and whether these cells can be further matured and reverse hyperglycaemia upon transplantation. MATERIALS AND METHODS The hESCs were sequentially treated with serum, activin and retinoic acid (RA) during embryoid body formation. The patterns of gene expression and protein production associated with embryonic germ layers and pancreatic endoderm were analysed by RT-PCR and immunostaining. The developmental competence and function of hESC-derived PDX1-positive cells were evaluated after in vivo transplantation. RESULTS Sequential treatment with serum, activin and RA highly upregulated the expression of the genes encoding forkhead box protein A2 (FOXA2), SRY-box containing gene 17 (SOX17), pancreatic and duodenal homeobox 1 (PDX1) and homeobox HB9 (HLXB9). The population of pancreatic endodermal cells that produced PDX1 was significantly increased at the expense of ectodermal differentiation, and a subset of the PDX1-positive cells also produced FOXA2, caudal-type homeobox transcription factor 2 (CDX2), and nestin (NES). After transplantation, the PDX1-positive cells further differentiated into mature cell types producing insulin and glucagon, resulting in amelioration of hyperglycaemia and weight loss in streptozotocin-treated diabetic mice. CONCLUSIONS/INTERPRETATION Our strategy allows the progressive differentiation of hESCs into pancreatic endoderm capable of generating mature pancreatic cell types that function in vivo. These findings may establish the basis of further investigations for the purification of transplantable islet progenitors derived from hESCs.
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Affiliation(s)
- J H Shim
- Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, West Building/Room 304, Science Campus, 1 Anam-dong 5-ga, Sungbuk-goo, Seoul 136-713, Republic of Korea
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Gangaram-Panday ST, Faas MM, de Vos P. Towards stem-cell therapy in the endocrine pancreas. Trends Mol Med 2007; 13:164-73. [PMID: 17307397 DOI: 10.1016/j.molmed.2007.02.002] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2006] [Revised: 01/18/2007] [Accepted: 02/06/2007] [Indexed: 02/07/2023]
Abstract
Many approaches of stem-cell therapy for the treatment of diabetes have been described. One is the application of stem cells for replacement of nonfunctional islet cells in the native endogenous pancreas; another one is the use of stem cells as an inexhaustible source for islet-cell transplantation. During recent years three types of stem cells have been investigated: embryonic stem cells, bone-marrow-derived stem cells and organ-bound stem cells. We discuss the advantages and limitations of these different cell types. The applicability for the treatment of dysfunction of beta cells in the pancreas has been demonstrated for all three cell types, but more-detailed understanding of the sequence of events during differentiation is required to produce fully functional insulin-producing cells.
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Affiliation(s)
- Shanti T Gangaram-Panday
- Transplantation Biology and Immunoendocrinology, Section of Medical Biology, Department of Pathology and Laboratory Medicine, University Medical Centre Groningen, Groningen, The Netherlands.
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Yue F, Cui L, Johkura K, Ogiwara N, Sasaki K. Glucagon-like peptide-1 differentiation of primate embryonic stem cells into insulin-producing cells. ACTA ACUST UNITED AC 2006; 12:2105-16. [PMID: 16968152 DOI: 10.1089/ten.2006.12.2105] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
The present study was performed to determine whether glucagon-like peptide-1 (GLP-1) stimulates differentiation of nestin-selected embryonic stem cells into insulin-producing cells. Our experimental strategy began with the production of a highly enriched population of nestin-positive cells from embryoid bodies. These cells differentiated into insulin-producing cells after addition of GLP-1. Islet-like cell clusters (ICCs) formed in inducing culture. These nestin-positive cell-derived ICCs expressed numerous beta-cell lineage genes, including insulin; Glut-2; pancreatic duodenal homebox-1 protein (PDX-1); islet amyloid polypeptide (IAPP); neurogenin 3 (ngn3); and alpha, gamma, and delta cell gene markers. Cells of ICCs showed increased insulin protein expression, glucose-dependent insulin release, and coexpression of insulin and C-peptide. In addition, ICCs were characterized by coexpression of nestin/insulin and nestin/PDX-1. The levels of pancreas-related gene and protein expression and insulin secretion in the GLP-1 group were stronger than those in the normal controls. GLP-1 has been shown to be involved in stimulating the signaling pathways downstream of the transcription factor PDX-1, by increasing its protein and messenger RNA levels. In vivo, ICCs displayed the ability to reverse hyperglycemia in diabetic severe combined immunodeficiency (SCID) mice. We concluded that GLP-1 induced differentiation of nestin-positive progenitor embryonic stem cells into insulin-producing cells, which was achieved by upregulation of PDX-1 expression. This method may have future applications in stem cell therapy of diabetes.
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Affiliation(s)
- Fengming Yue
- Department of Anatomy and Organ Technology, Institute of Organ Transplants, Reconstructive Medicine and Tissue Engineering, Shinshu University Graduate School of Medicine, Nagano, Japan.
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Lin HT, Chiou SH, Kao CL, Shyr YM, Hsu CJ, Tarng YW, Ho LLT, Kwok CF, Ku HH. Characterization of pancreatic stem cells derived from adult human pancreas ducts by fluorescence activated cell sorting. World J Gastroenterol 2006; 12:4529-35. [PMID: 16874866 PMCID: PMC4125641 DOI: 10.3748/wjg.v12.i28.4529] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To isolate putative pancreatic stem cells (PSCs) from human adult tissues of pancreas duct using serum-free, conditioned medium. The characterization of surface phenotype of these PSCs was analyzed by flow cytometry. The potential for pancreatic lineage and the capability of β-cell differentiation in these PSCs were evaluated as well.
METHODS: By using serum-free medium supplemented with essential growth factors, we attempted to isolate the putative PSCs which has been reported to express nestin and pdx-1. The Matrigel™ was employed to evaluate the differential capacity of isolated cells. Dithizone staining, insulin content/secretion measurement, and immunohistochemistry staining were used to monitor the differentiation. Fluorescence activated cell sorting (FACS) was used to detect the phenotypic markers of putative PSCs.
RESULTS: A monolayer of spindle-like cells was cultivated. The putative PSCs expressed pdx-1 and nestin. They were also able to differentiate into insulin-, glucagon-, and somatostatin-positive cells. The spectrum of phenotypic markers in PSCs was investigated; a similarity was revealed when using human bone marrow-derived stem cells as the comparative experiment, such as CD29, CD44, CD49, CD50, CD51, CD62E, PDGFR-α, CD73 (SH2), CD81, CD105(SH3).
CONCLUSION: In this study, we successfully isolated PSCs from adult human pancreatic duct by using serum-free medium. These PSCs not only expressed nestin and pdx-1 but also exhibited markers attributable to mesenchymal stem cells. Although work is needed to elucidate the role of these cells, the application of these PSCs might be therapeutic strategies for diabetes mellitus.
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Affiliation(s)
- Han-Tso Lin
- Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, 11217, Taiwan, China
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Abstract
The need for a reliable source of functional beta cells has led to many new investigations in an effort to drive the differentiation of embryonic stem cells, of putative stem cells, or of pancreatic progenitor cells to form new beta cells. There appears to be a plasticity of pancreatic cells in vitro that may be exploited to generate the necessary beta cells. Major questions still remain: whether there are true pancreatic stem cells, what are the pancreatic progenitor cells after birth, and whether expanded beta cells themselves could serve as the source.
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Affiliation(s)
- Akari Inada
- Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA
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Abstract
Current understanding of the biology of epidermal stem cells opens a totally new perspective in the function of the epidermis and adjacent epithelial structures. A number of pathogenetic as well as clinical-therapeutic approaches against a variety of dermatoses may become possible with knowledge about keratinocyte proliferation, differentiation and regeneration. The reservoir of epidermal stem cells is located in the interfollicular epidermis, the hair follicle area and the germinal hair follicle matrix. Endogenous stem cell clones exist here, giving rise to transient amplifying cells and postmitotic cells. The stem cell clones are organized in clusters and display high expression of adhesion proteins, which guarantee their stability in a specific environment consisting of different cell types and extracellular substrates in the stratum basale. Differentiation is determined by a specific cascade of chemical signals from the stem cell environment and from the genetic program of the cell. The clinical relevance of stem cells lies primarily in their therapeutic potential with reconstruction of epithelia by reimplantation of autologous stem cells or gene therapeutic applications such as targeted transfection. However, the benefit-to-risk ratio cannot yet be accurately estimated.
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Affiliation(s)
- Karin Rzepka
- Institut für angewandte Dermatopharmazie, Martin-Luther-Universität Halle-Wittenberg
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