scholarly journals Encapsulated Glucagon-Like Peptide-1-Producing Mesenchymal Stem Cells Have a Beneficial Effect on Failing Pig Hearts

2012 ◽  
Vol 1 (10) ◽  
pp. 759-769 ◽  
Author(s):  
Elizabeth J. Wright ◽  
Kelly A. Farrell ◽  
Nadim Malik ◽  
Moustapha Kassem ◽  
Andrew L. Lewis ◽  
...  
Neurosurgery ◽  
2015 ◽  
Vol 78 (4) ◽  
pp. E596-E600 ◽  
Author(s):  
Makoto Nakamura ◽  
Amir Samii ◽  
Josef M. Lang ◽  
Friedrich Götz ◽  
Madjid Samii ◽  
...  

Abstract BACKGROUND AND IMPORTANCE: Local biological drug delivery in the brain is an innovative field of medicine that developed rapidly in recent years. Our report illustrates a unique case of de novo development of a cerebral arteriovenous malformation (AVM) after implantation of genetically modified allogeneic mesenchymal stem cells in the brain. CLINICAL PRESENTATION: A 50-year-old man was included in a prospective clinical study (study ID number CM GLP-1/01, 2007-004516-31) investigating a novel neuroprotective approach in stroke patients to prevent perihematomal neuronal damage. In this study, alginate microcapsules containing genetically modified allogeneic mesenchymal stem cells producing the neuroprotective glucagon-like peptide-1 (GLP-1) were implanted. Three years later, the patient presented with aphasia and a focal seizure due to a new left frontal intracerebral hemorrhage. Angiography revealed a de novo left frontal AVM. CONCLUSION: The development of an AVM within a period of 3 years after implantation of the glucagon-like peptide-1–secreting mesenchymal stem cells suggests a possible relationship. This case exemplifies that further investigations are necessary to assess the safety of genetically modified cell lines for local biological drug delivery in the brain.


2010 ◽  
Vol 298 (3) ◽  
pp. E634-E643 ◽  
Author(s):  
C. Sanz ◽  
P. Vázquez ◽  
C. Blázquez ◽  
P. A. Barrio ◽  
M. Del M. Alvarez ◽  
...  

Glucagon-like peptide 1 (GLP-1) functions as an incretin hormone with antidiabetogenic properties. However, the role of GLP-1 in human bone marrow-derived mesenchymal stem cells (hMSCs), if any, remains unknown. The effects of GLP-1 on hMSCs were tested with regard to cell proliferation, cytoprotection, and cell differentiation into adipocytes. The signaling pathways involved in these processes were also analyzed. Cells were characterized with biochemical and morphological approaches before and after being induced to differentiate into adipocytes. PCNA protein levels were used as a proliferation index, whereas cell apoptosis was studied by deprivation of fetal bovine serum. Isolated hMSCs expressed stem cell markers as well as mRNA and GLP-1 receptor protein. GLP-1 increased the proliferation of hMSCs, which decreased when they were induced to differentiate into adipocytes. This process produced biochemical and morphological changes in cells expressing PPARγ, C/EBPβ, AP2, and LPL in a time-dependent pattern. Notably, GLP-1 significantly reduced the expression of PPARγ, C/EBPβ, and LPL. These effects were exerted at least through the MEK and PKC signaling pathways. In addition, GLP-1 significantly reduced cell apoptosis. Our data indicate that, in hMSCs, GLP-1 promotes cellular proliferation and cytoprotection and prevents cell differentiation into adipocytes. These latter findings underscore the potential therapeutic role of GLP-1 in preventing the adipocyte hyperplasia associated with obesity and, additionally, could bolster the maintenance of hMSC stores by promoting the proliferation and cytoprotection of undifferentiated hMSC.


2012 ◽  
Vol 30 (4) ◽  
pp. 315-324 ◽  
Author(s):  
Christine Wallrapp ◽  
Eric Thoenes ◽  
Frank Thürmer ◽  
Anette Jork ◽  
Moustapha Kassem ◽  
...  

2021 ◽  
Author(s):  
Sama Abdulmalik ◽  
Daisy Ramos ◽  
Swetha Rudraiah ◽  
Yeshavanth Kumar Banasavadi-Siddegowda ◽  
Sangamesh G. Kumbar

2014 ◽  
Vol 29 (4) ◽  
pp. 567 ◽  
Author(s):  
Yun Kyung Jeon ◽  
Min Jung Bae ◽  
Ju In Kim ◽  
Joo Hyoung Kim ◽  
Soo Jong Choi ◽  
...  

2005 ◽  
Vol 186 (2) ◽  
pp. 343-352 ◽  
Author(s):  
L Bai ◽  
G Meredith ◽  
B E Tuch

Embryonic stem cells (ESCs) can be differentiated into insulin-producing cells by a five-stage procedure involving altering culture conditions and addition of nicotinamide. The amounts of insulin in these cells are lower than those found in pancreatic β cells. Glucagon-like peptide-1 (GLP-1) induces the differentiation of β cells from ductal progenitor cells. We examined the possibility of GLP-1, and its long-acting agonist exendin-4, enhancing the differentiation of insulin-producing cells from mouse ESCs (mESCs). A five-stage culturing strategy starting with embryoid bodies (EBs) was used in this study. mRNA for pancreatic duodenal homeobox gene 1 (PDX-1) and neurogenic differentiation (NeuroD) was detected from stage 1, hepatocyte nuclear factor 3 beta (HNF3β) and insulin 2 from stage 2, Ngn3 and glucose transporter 2 (GLUT2) from stage 3, and insulin 1 and other β-cell markers, at stages 4–5. Cells at stage 5 secreted C-peptide, being 0.68 ± 0.01 pmol/106 cells per 2 days, and had an immunoreactive insulin content of 13.5 ± 0.7 pmol/106 cells. Addition of GLP-1 (100 nM) and nicotinamide (10 mM) at stage 5 resulted in a 50% and 48% increase in insulin content and C-peptide secretion respectively compared with nicotinamide alone. Glucose-induced insulin secretion was enhanced 4-fold by addition of both growth factors. The GLP-1 receptor was present at all five stages of the culture. Addition of exendin-4 to cells at stage 2 resulted in a 4.9-fold increase in expression of the gene for insulin 1 and a 2-fold increase in insulin content compared with the effect of nicotinamide alone at stage 5. It is concluded that both GLP-1 and exendin-4 enhance the level of expression of insulin in glucose-responsive insulin-producing cells derived from the R1 mESC line.


Sign in / Sign up

Export Citation Format

Share Document