<i>Pdx1</i>and controlled culture conditions induced differentiation of human amniotic fluid-derived stem cells to insulin-producing clusters

Chun, So Young; Mack, David L.; Moorefield, Emily C.; Oh, Se Heang; Kwon, Tae Gyun; Pettenati, Mark J.; Yoo, James J.; Coppi, Paolo De; Atala, Anthony; Söker, Shay

doi:10.1002/term.1631

Cited by 26 publications

(13 citation statements)

References 64 publications

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“…The human AFSC were proposed as a potential source of insulin-secreting cells [29, 30]. Forty eight hours post seeding the cells spread on the surface of the acellular pancreas ECM (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…We tested the cell compatibility of the acellular porcine pancreas by seeding hAFSC, as a potential stem cell source for generation of β cells [29, 30]. Islet tissue only comprises 1–2% of the adult human pancreas, and the non-islet support cells may be essential for islet viability and function [52]; as well, stromal cells seem to be essential for supporting growth and differentiation of progenitor cells [53].…”

Section: Discussionmentioning

confidence: 99%

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Porcine pancreas extracellular matrix as a platform for endocrine pancreas bioengineering

et al. 2013

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Emergent technologies of regenerative medicine have the potential to overcome the limitations of organ transplantation by supplying tissues and organs bioengineered in the laboratory. Pancreas bioengineering requires a scaffold that approximates the biochemical, spatial and vascular relationships of the native extracellular matrix (ECM). We describe the generation of a whole organ, three-dimensional pancreas scaffold using acellular porcine pancreas. Imaging studies confirm that our protocol effectively removes cellular material while preserving ECM proteins and the native vascular tree. The scaffold was seeded with human stem cells and porcine pancreatic islets, demonstrating that the decellularized pancreas can support cellular adhesion and maintenance of cell functions. These findings advance the field of regenerative medicine towards the development of a fully functional, bioengineered pancreas capable of establishing and sustaining euglycemia and may be used for transplantation to cure diabetes mellitus.

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“…The human AFSC were proposed as a potential source of insulin-secreting cells [29, 30]. Forty eight hours post seeding the cells spread on the surface of the acellular pancreas ECM (Fig.…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Porcine pancreas extracellular matrix as a platform for endocrine pancreas bioengineering

et al. 2013

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“…Pancreatic extracellular matrix biocompatibility was tested by the static short-term (7 days) cellular seeding with human amniotic fluid stem cells. This type of cells has been also proposed as a potential source of insulin-secreting cells [127]. To validate the hypothetical capacity of acellular ECMbased pancreas like scaffold to sustain endocrine pancreatic function, porcine pancreas scaffold was repopulated with porcine islets and insulin secretion was ex-vivo measured under different glucose stimula and at several time points.…”

Section: Large Animal Modelsmentioning

confidence: 99%

Bioengineering the Pancreas: Cell-on-Scaffold Technology

Peloso¹,

Citro²,

Oldani³

et al. 2017

Scaffolds in Tissue Engineering - Materials, Technologies and Clinical Applications

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Nowadays, type I diabetes mellitus is a pathology afflicting millions of people globally with a dramatic assessment in the next future. Current treatments including exogenous insulin, pancreas transplantation and islets transplantation, are not free from important lifelong side effects. In the last decade, tissue engineering and regenerative medicine have shown encouraging results about the possibility to produce a functional bioengineered pancreas. Among many technologies, decellularization offers the opportunity to produce an organ-specific acellular matrix that could subsequently repopulate with endocrine cellular population. Herein, we aim to review the state-of-art and this technology highlighting the diabetes burden for the healthcare system and the major achievements toward the manufacturing of a bioengineered pancreas obtained by cell-on-scaffold technology.

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“…found that small interfering ribonucleic acid pancreatic and duodenal homeobox‐1 ( Pdx‐1 )‐transfected CD44 + /CD105 + human amniotic fluid cells could not fully differentiate into β‐cell‐like cells, suggesting that Pdx‐1 played an important role in the induction of CD44 + /CD105 + human amniotic fluid cells into pancreatic β‐cell‐like cells in vitro . Recent evidence has shown that hAFSCs can be modified to a β‐cell phenotype by overexpression of pancreatic transcription factors, such as Pdx‐1 . In addition, Gage et al .…”

Section: Introductionmentioning

confidence: 99%

Enhanced differentiation of human amniotic fluid‐derived stem cells into insulin‐producing cells in vitro

Ren

Yan

et al. 2016

J of Diabetes Invest

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Aims/IntroductionTo investigate the ability of human amniotic fluid stem cells (hAFSCs) to differentiate into insulin‐producing cells.Materials and Methods hAFSCs were induced to differentiate into pancreatic cells by a multistep protocol. The expressions of pancreas‐related genes and proteins, including pancreatic and duodenal homeobox‐1, insulin, and glucose transporter 2, were detected by polymerase chain reaction and immunofluorescence. Insulin secreted from differentiated cells was tested by enzyme‐linked immunosorbent assay.Results hAFSCs were successfully isolated from amniotic fluid that expressed the pluripotent markers of embryonic stem cells, such as Oct3/4, and mesenchymal stem cells, such as integrin β‐1 and ecto‐5′‐nucleotidase. Here, we first obtained the hAFSCs that expressed pluripotent marker stage‐specific embryonic antigen 1. Real‐time polymerase chain reaction analysis showed that pancreatic and duodenal homeobox‐1, paired box gene 4 and paired box gene 6 were expressed in the early phase of induction, and then stably expressed in the differentiated cells. The pancreas‐related genes, such as insulin, glucokinase, glucose transporter 2 and Nkx6.1, were expressed in the differentiated cells. Immunofluorescence showed that these differentiated cells co‐expressed insulin, C‐peptide, and pancreatic and duodenal homeobox‐1. Insulin was released in response to glucose stimulation in a manner similar to that of adult human islets.ConclusionsThe present study showed that hAFSCs, under selective culture conditions, could differentiate into islet‐like insulin‐producing cells, which might be used as a potential source for transplantation in patients with type 1 diabetes mellitus.

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Pdx1and controlled culture conditions induced differentiation of human amniotic fluid-derived stem cells to insulin-producing clusters

Cited by 26 publications

References 64 publications

Porcine pancreas extracellular matrix as a platform for endocrine pancreas bioengineering

Porcine pancreas extracellular matrix as a platform for endocrine pancreas bioengineering

Bioengineering the Pancreas: Cell-on-Scaffold Technology

Enhanced differentiation of human amniotic fluid‐derived stem cells into insulin‐producing cells in vitro

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