Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.
Advertisement
Islet transplantation in 2022
Nature Reviews Endocrinology (2022)
3
Metrics details
The year 2022 has been notable for game-changing early progress in clinical trials with stem cell islets; durable and promising 20-year data with long-term outcomes in clinical islet transplantation; and the development of locally protective or gene-editing-based approaches to avoid long-term immunosuppression.
ViaCyte Inc.’s PEC-01 trials with subcutaneous implantation of embryonic stem cell islets (SCIs) resulted in islet survival and detectable levels of C-peptide in peripheral blood; full immunosuppression was needed3.
Durable 20-year outcomes with human intraportal islet transplantation with sustained metabolic response were reported; full immunosuppression was needed5.
Islets were cotransplanted with protective mesenchymal stem cells that secreted CTLA4 and PDL1 in mice, leading to sustained allograft survival without immunosuppression7.
Detailed characterizations of the functional properties of mature SCIs were carried out, benchmarked against human islets, highlighting the need for thorough characterization to ensure future clinical product safety8.
A mixed lymphocyte response was used to target chemokine ligand 10 (CXCL10) pathways that prevent immune activation as a screening tool for CRISPR gene-editing targets10.
The Vertex trial followed closely on the heels of two ground-breaking reports3,4 from ViaCyte Inc. (owned now by Vertex), in which embryonic stem cell-derived islet progenitor cells (PEC-01) were surgically implanted within small (1.5 cm × 1 cm) devices beneath the skin. These two reports showed the implants to be safe, well tolerated and without risk of off-target growth. Insulin expression within β-cells was present in 63% of units at 3–12 months after transplantation, with a predominance of α-cells reflecting the immature state of the graft. Meal-responsive C-peptide was evident by 26 weeks3, and in the second report measurable serum levels of C-peptide were present in one-third of patients4. These results are impressive, considering the unfavourable nature of the hypoxic subcutaneous environment.
This is a preview of subscription content, access via your institution
Subscribe to Journal
Get full journal access for 1 year
73,83 €
only 6,15 € per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Buy article
Get time limited or full article access on ReadCube.
$32.00
All prices are NET prices.
Kolata, G. A. Cure for type 1 diabetes? For one man, it seems to have worked. The New York Times https://www.nytimes.com/2021/11/27/health/diabetes-cure-stem-cells.html (2021).
Banting, F. G., Best, C. H., Collip, J. B., Campbell, W. R. & Fletcher, A. A. Pancreatic extracts in the treatment of diabetes mellitus. CMAJ 12, 141–146 (1922).
CAS Google Scholar
Ramzy, A. et al. Implanted pluripotent stem-cell-derived pancreatic endoderm cells secrete glucose-responsive C-peptide in patients with type 1 diabetes. Cell Stem Cell 28, 2047–2061.e5 (2021).
Article CAS Google Scholar
Shapiro, A. M. J. et al. Insulin expression and C-peptide in type 1 diabetes subjects implanted with stem cell-derived pancreatic endoderm cells in an encapsulation device. Cell Rep. Med. 2, 100466 (2021).
Article CAS Google Scholar
Marfil-Garza, B. A. et al. Pancreatic islet transplantation in type 1 diabetes: 20-year experience from a single-centre cohort in Canada. Lancet Diabetes Endocrinol. 10, 519–532 (2022).
Article CAS Google Scholar
Hering, B. J. et al. Factors associated with favourable 5 year outcomes in islet transplant alone recipients with type 1 diabetes complicated by severe hypoglycaemia in the Collaborative Islet Transplant Registry. Diabetologia https://doi.org/10.1007/s00125-022-05804-4 (2022).
Article Google Scholar
Wang, X. et al. Engineered immunomodulatory accessory cells improve experimental allogeneic islet transplantation without immunosuppression. Sci. Adv. 8, eabn0071 (2022).
Article CAS Google Scholar
Balboa, D. et al. Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells. Nat. Biotechnol. 40, 1042–1055 (2022).
Article CAS Google Scholar
Sluch, V. M. et al. CRISPR-editing of hESC’s allows for production of immune evasive cells capable of differentiation to pancreatic progenitors for future type 1 diabetes therapy. Diabetologia https://www.ipscell.com/wp-content/uploads/2019/09/ViaCyte-CRISPR-EASD-Abstract-September-2019.pdf (2019).
Sintov, E. et al. Whole-genome CRISPR screening identifies genetic manipulations to reduce immune rejection of stem cell-derived islets. Stem Cell Reports 17, 1976–1990 (2022).
Article CAS Google Scholar
Download references
Department of Surgery, Clinical Islet Transplant Program, University of Alberta, Edmonton, Alberta, Canada
A. M. James Shapiro & Kevin Verhoeff
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
A. M. James Shapiro & Kevin Verhoeff
You can also search for this author in PubMed Google Scholar
You can also search for this author in PubMed Google Scholar
Correspondence to A. M. James Shapiro.
A.M.J.S. holds a Canada Research Chair in Regenerative Medicine and Transplantation Surgery, and receives funding from the Canadian Stem Cell Network, the Juvenile Diabetes Research Foundation, the Diabetes Research Institute Foundation of Canada and the University Hospital Foundation. He consults for ViaCyte Inc., Protokinetix Inc., Hemostemix Inc. and Aspect Biosystems Ltd. K.V. declares no competing interests.
Reprints and Permissions
Shapiro, A.M.J., Verhoeff, K. A spectacular year for islet and stem cell transplantation. Nat Rev Endocrinol (2022). https://doi.org/10.1038/s41574-022-00790-4
Download citation
Published: 20 December 2022
DOI: https://doi.org/10.1038/s41574-022-00790-4
Anyone you share the following link with will be able to read this content:
Sorry, a shareable link is not currently available for this article.
Provided by the Springer Nature SharedIt content-sharing initiative
Advertisement
© 2022 Springer Nature Limited
Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.