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Chronic Pancreatitis Patient Mesenchymal Stem Cells Can Support Islet Grafting

Review of “Mesenchymal Stem Cells from Chronic Pancreatitis Patients Show Comparable Potency Compared to Cells from Healthy Donors” from STEM CELLS Translational Medicine by Stuart P. Atkinson 

Recent research from the laboratory of Hongjun Wang (Medical University of South Carolina, USA) established that cotransplantation of syngeneic mouse islet with mesenchymal stem cells (MSCs) derived from patients suffering from chronic pancreatitis, a long‐standing inflammatory condition associated with endocrine and exocrine dysfunction [1, 2], fostered enhanced islet survival and function [3]. Furthermore, recent data from a pilot clinical trial of autologous islet cotransplantation for human patients undergoing total pancreatectomy also established the potential protective effects of chronic pancreatitis MSCs on islet grafts [4]. 

Now the team returns with a new STEM CELLS Translational Medicine that thoroughly assessed the suitability of MSCs derived from human chronic pancreatitis patients for regenerative cell therapy by comparing phenotype and functionality to MSCs derived from healthy donors [5]. Wang et al. now suggest that chronic pancreatitis patient MSCs display general similarities to healthy MSCs, thereby promoting their application as autologous cell therapy in patients undergoing total pancreatectomy with islet transplantation.

Overall, the comparisons made suggested an overall similarity between healthy and pancreatitis patient MSCs with regards to cell surface markers, colony formation, multilineage differentiation, secretion of vascular endothelial growth factor and transforming growth factor-beta, senescence, and inhibition of T cells proliferation in vitro. Importantly, this latter ability suggests that pancreatitis patient MSCs retain their immunosuppressive characteristics.

However, the analysis of MSC‐related gene expression established the disruption of gene expression related to angiogenesis, via the downregulation of growth differentiation factor 6 and hepatocyte growth factor and upregulation of matrix metalloproteinase‐2, and immunomodulatory function via the upregulation of transforming growth factor-beta and interferon‐γ‐induced indoleamine 2, 3‐dioxygenase in pancreatitis patient MSCs. Additionally, the study also revealed that pancreatitis patient MSCs also secreted lower levels of hepatocyte growth factor.

Even given these differences, the authors report that both populations of MSCs displayed a similar therapeutic capacity, as measured by their ability to prevent the hypoxia‐induced death of pancreatic β cells in an in vitro cell culture system [6], an encouraging finding for the application of autologous cell therapy.

In summary, while the authors highlight differences in gene expression, profiles pancreatitis patient MSCs display a broad similarity of healthy MSCs with regards to their immunomodulatory and prosurvival abilities, thereby justifying the cotransplantation of autologous MSC to improve islet transplantation outcomes.

For more on the therapeutic potential of MSCs and new strategies to improve islet transplantation, stay tuned to the Stem Cells Portal.

References

  1. Yadav D, Timmons L, Benson JT, et al., Incidence, prevalence, and survival of chronic pancreatitis: a population-based study. American Journal of Gastroenterology 2011;106:2192-9.
  2. Radomski M and Zureikat AH, Total pancreatectomy and islet cell autotransplantation: outcomes, controversies and new techniques. Journal of the Pancreas 2015;16:1-10.
  3. Song L, Sun Z, Kim DS, et al., Adipose stem cells from chronic pancreatitis patients improve mouse and human islet survival and function. Stem Cell Reseach and Therapy 2017;8:192.
  4. Wang H, Strange C, Nietert PJ, et al., Autologous Mesenchymal Stem Cell and Islet Cotransplantation: Safety and Efficacy. STEM CELLS Translational Medicine 2018;7:11-19.
  5. Wang J, Zhang Y, Cloud C, et al., Mesenchymal Stem Cells from Chronic Pancreatitis Patients Show Comparable Potency Compared to Cells from Healthy Donors. STEM CELLS Translational Medicine 2019;8:418-429.
  6. Wang H, Wang J, Cloud C, et al., Comparison of mesenchymal stem cells from healthy donor and chronic pancreatitis patients. Cytotherapy 2018;20:S56-S57.