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Updated: Jun 4, 2026
Isolation, Culture, and Imaging of Human Fetal Pancreatic Cell Clusters
Published on: May 18, 2014
Reduced immunogenicity of pancreatic progenitor cells derived from first-trimester human fetal pancreas
Man Ting Ma1, Kwan Keung Leung, Kam Sze Tsang
1School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Insights
First-trimester human fetal pancreatic progenitor cells and islet-like cell clusters exhibit lower immunogenicity. These findings are crucial for developing safer cell-based therapies for diabetes, utilizing less immunogenic fetal stem cells.
Area of Science:
- Immunology
- Developmental Biology
- Stem Cell Biology
Background:
- Fetal stem cells offer low immunogenicity and tumorigenicity for transplantation.
- Human fetal pancreatic progenitor cells (PPCs) can differentiate into insulin-producing islet-like cell clusters (ICCs).
- The immunological profile of these fetal-derived pancreatic cells requires characterization for therapeutic applications.
Purpose of the Study:
- To compare the immunogenicity of first- and second-trimester human fetal pancreatic progenitor cells (PPCs) and islet-like cell clusters (ICCs).
- To investigate the expression of immune-related genes and co-stimulatory molecules in these cells.
- To assess the functional alloreactivity of PPCs in mixed lymphocyte reactions (MLRs).
Main Methods:
- Polymerase chain reaction (PCR) was used to detect immune gene expression (MHC-I, MHC-II, C3, CCL19, TNFSF10, CD80, CD86).
- Cells were treated with interferon-gamma (IFN-γ) to assess changes in MHC molecule expression.
- Mixed lymphocyte reactions (MLRs) were performed using peripheral blood mononuclear cells (PBMCs) to evaluate functional alloreactivity.
Main Results:
- PPCs and ICCs express immune genes (MHC-I, MHC-II, C3, CCL19, TNFSF10) but lack co-stimulatory genes (CD80, CD86).
- Second-trimester PPCs showed higher MHC-I and MHC-II expression than first-trimester PPCs, which increased further after IFN-γ treatment.
- Second-trimester PPCs induced greater PBMC proliferation and IFN-γ production in MLRs compared to first-trimester PPCs.
Conclusions:
- First-trimester human fetal PPCs and ICCs possess distinctively lower immunogenicity compared to second-trimester cells.
- Even under pro-inflammatory conditions (IFN-γ challenge), first-trimester cells maintained lower immunogenicity.
- These findings suggest that first-trimester fetal pancreatic cells are more suitable for transplantation therapies due to their reduced immunogenic potential.
Abstract:
The relatively low immunogenic and tumorigenic nature of fetal stem cells makes them attractive candidates for transplantation. Pancreatic progenitor cells (PPCs) derived from human fetal pancreas that are amenable to growth and differentiation into transplantable insulin-producing islet-like cell clusters (ICCs) have been reported recently; however, the immunological nature of these cells has yet to be characterized. We thus investigated and compared the immunogenicity of pancreatic progenitor cells and islet-like cell clusters from first- and second-trimester human fetal pancreas. Polymerase chain reaction demonstrated that pancreatic progenitor cells and islet-like cell clusters express immune-related genes of major histocompatibility complex, MHC-I and MHC-II, complement component 3 (C3), chemokine ligand (CCL19), and tumor necrosis factor super family (TNFSF10), but no expression of the co-stimulatory genes, CD80 and CD86. Interestingly, pancreatic progenitor cells showed a differential expression of MHC-I and MHC-II with advancing gestational age with a greater expression in pancreatic progenitor cells from the second trimester. Pre-incubation of the second-trimester cells with interferon-γ (IFN-γ) increased MHC molecule expression. Functional alloreactivity of pancreatic progenitor cells was investigated via mixed lymphocyte reactions (MLRs). Relative to first-trimester pancreatic progenitor cells, second-trimester pancreatic progenitor cells induced a greater extent of proliferation of peripheral blood mononuclear cells (PBMCs) and resulted in more IFN-γ production in phytohaemagllutinin-stimulated peripheral blood mononuclear cells following co-culture. Results of the study indicated that first-trimester pancreatic progenitor cells and islet-like cell clusters have a distinctively lower immunogenicity relative to second-trimester pancreatic progenitor cells, even after a pro-inflammatory cytokine challenge.
