Pancreatic Stem Cells: Unresolved Business

Jiang, Fuming; Morahan, Grant

doi:10.5772/23760

Cited by 4 publications

(3 citation statements)

References 103 publications

(113 reference statements)

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“…Our study found that the combination of small molecules in PE induction medium, which consisted of taurine, retinoic acid (RA), FGF2, EGF, SB431542, dorsomorphin, nicotinamide (NIC), and DAPT, show the positive outcome, especially P.2.3. Here, the group treated with taurine alone revealed the hasty differentiation by the greater expression of endocrine percussor markers ( Nkx2.2 , Pax4 ), however, they showed the lowest expression of Pdx1 and Nkx6.1 , pancreatic endoderm and multipotent progenitor markers, which could cause the undesired commitments of the cell’s fates 88 , 89 . It is noticed that EGF, epidermal growth factor, could promote the proliferation of Sox9 / Pdx1 -positive pancreatic progenitors 90 .…”

Section: Discussionmentioning

confidence: 87%

In vitro generation of transplantable insulin-producing cells from canine adipose-derived mesenchymal stem cells

Rodprasert

Kuncorojakti

et al. 2022

Sci Rep

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Canine mesenchymal stem cells (cMSCs) have potential applications for regenerative therapy, including the generation of insulin-producing cells (IPCs) for studying and treating diabetes. In this study, we established a useful protocol for generating IPCs from canine adipose mesenchymal stem cells (cAD-MSCs). Subsequently, in vitro preservation of pluronic F127-coated alginate (ALGPA)-encapsulated cAD-MSC-derived IPCs was performed to verify ready-to-use IPCs. IPCs were induced from cAD-MSCs with the modulated three-stepwise protocol. The first step of definitive endoderm (DE) induction showed that the cooperation of Chir99021 and Activin A created the effective production of Sox17-expressed DE cells. The second step for pancreatic endocrine (PE) progenitor induction from DE indicated that the treatment with taurine, retinoic acid, FGF2, EGF, TGFβ inhibitor, dorsomorphin, nicotinamide, and DAPT showed the significant upregulation of the pancreatic endocrine precursor markers Pdx1 and Ngn3. The last step of IPC production, the combination of taurine, nicotinamide, Glp-1, forskolin, PI3K inhibitor, and TGFβ inhibitor, yielded efficiently functional IPCs from PE precursors. Afterward, the maintenance of ALGPA-encapsulated cAD-MSC-derived IPCs with VSCBIC-1, a specialized medium, enhanced IPC properties. Conclusion, the modulated three-stepwise protocol generates the functional IPCs. Together, the encapsulation of cAD-MSC-derived IPCs and the cultivation with VSCBIC-1 enrich the maturation of generated IPCs.

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Section: Discussionmentioning

confidence: 87%

In vitro generation of transplantable insulin-producing cells from canine adipose-derived mesenchymal stem cells

Rodprasert

Kuncorojakti

et al. 2022

Sci Rep

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“…The existence of adult pancreatic stem cells has been debated for years 52 . Given the full lineage potential of the primitive bud to give rise to both exocrine and endocrine cells, our study provides direct evidence for the existence of pancreatic stem cells, which should reside in the primitive bud.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Liraglutide Administration Induces Pancreas Neogenesis in Adult T2DM Mice

Deng

Yang

et al. 2020

Cell Transplant

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In vivo beta-cell neogenesis may be one way to treat diabetes. We aimed to investigate the effect of glucagon-like peptide-1 (GLP-1) on beta-cell neogenesis in type 2 diabetes mellitus (T2DM). Male C57BL/6J mice, 6 wk old, were randomly divided into three groups: Control, T2DM, and T2DM + Lira. T2DM was induced using high-fat diet and intraperitoneal injection of streptozotocin (40 mg/kg/d for 3 d). At 8 wk after streptozotocin injection, T2DM + Lira group was injected intraperitoneally with GLP-1 analog liraglutide (0.8 mg/kg/d) for 4 wk. Apparently for the first time, we report the appearance of a primitive bud connected to pancreas in all adult mice from each group. The primitive bud was characterized by scattered single monohormonal cells expressing insulin, GLP-1, somatostatin, or pancreatic polypeptide, and four-hormonal cells, but no acinar cells and ductal epithelial cells. Monohormonal cells in it were small, newborn, immature cells that rapidly proliferated and expressed cell markers indicative of immaturity. In parallel, Ngn3+ endocrine progenitors and Nestin+ cells existed in the primitive bud. Liraglutide facilitated neogenesis and rapid growth of acinar cells, pancreatic ducts, and blood vessels in the primitive bud. Meanwhile, scattered hormonal cells aggregated into cell clusters and grew into larger islets; polyhormonal cells differentiated into monohormonal cells. Extensive growth of exocrine and endocrine glands resulted in the neogenesis of immature pancreatic lobes in adult mice of T2DM + Lira group. Contrary to predominant acinar cells in mature pancreatic lobes, there were still a substantial number of mesenchymal cells around acinar cells in immature pancreatic lobes, which resulted in the loose appearance. Our results suggest that adult mice preserve the capacity of pancreatic neogenesis from the primitive bud, which liraglutide facilitates in adult T2DM mice. To our knowledge, this is the first time such a phenomenon has been reported.

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“…Our study found that the combination of small molecules in PE induction medium, which consisted of taurine, retinoic acid (RA), FGF2, EGF, SB431542, dorsomorphin, nicotinamide (NIC), and DAPT, show the positive outcome, especially P.2.3. Here, the group treated with taurine alone revealed the hasty differentiation by the greater expression of endocrine precursor markers (Nkx2.2, Pax4), however, they showed the lowest expression of Pdx1 and Nkx6.1, pancreatic endoderm and multipotent progenitor markers, which could cause the undesired commitments of the cell's fates (Zaret and Grompe, 2008;Jiang and Morahan, 2011). It is noticed that EGF, fibroblast growth factor, could promote the proliferation of Sox9/Pdx1-positive pancreatic progenitors (Konagaya and Iwata, 2019).…”

Section: Chapter V Discussionmentioning

confidence: 89%

In vitro generation of transplantable insulin-producing cells from canine adipose-derived mesenchymal stem cells

Dang

View full text Add to dashboard Cite

Canine mesenchymal stem cells (cMSCs) have potential applications for regenerative therapy, including the generation of insulin-producing cells (IPCs) for studying and treating diabetes. In this study, we established a useful protocol for generating IPCs from canine adipose mesenchymal stem cells (cAD-MSCs). Subsequently, in vitro preservation of pluronic F127-coated alginate (ALGPA)-encapsulated cAD-MSC-derived IPCs was performed to verify ready-to-use (RTU) IPCs. IPCs were induced from cAD-MSCs with the modulated three-stepwise protocol. The first step of definitive endoderm (DE) induction showed that the cooperation of Chir99021 and Activin A created the effective production of Sox17-expressed DE cells. The second step for pancreatic endocrine (PE) progenitor induction from DE indicated that the treatment with taurine, retinoic acid (RA), FGF2, EGF, TGF? inhibitor, dorsomorphin, nicotinamide (NIC), and DAPT show the significant upregulation of the PE precursor markers Pdx1 and Ngn3. The last step of IPC production, the combination of taurine, NIC, GLP-1, forskolin, PI3K inhibitor, and TGF? inhibitor, yielded efficiently functional IPCs from PE precursors. Afterward, the maintenance of ALGPA-encapsulated cAD-MSC-derived IPCs with VSCBIC-1, a specialized medium, enhanced IPC properties. Conclusion, the modulated three-stepwise protocol generates the functional IPCs. Together, the encapsulation of cAD-MSC-derived IPCs and the cultivation with VSCBIC-1 enrich the maturation of generated IPCs.

show abstract

Pancreatic Stem Cells: Unresolved Business

Cited by 4 publications

References 103 publications

In vitro generation of transplantable insulin-producing cells from canine adipose-derived mesenchymal stem cells

In vitro generation of transplantable insulin-producing cells from canine adipose-derived mesenchymal stem cells

Long-Term Liraglutide Administration Induces Pancreas Neogenesis in Adult T2DM Mice

In vitro generation of transplantable insulin-producing cells from canine adipose-derived mesenchymal stem cells

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