Exciting Advancements in Cell Replacement Therapy
ViaCyte, a beta cell replacement company long supported by JDRF, has developed and tested three separate stem cell-based islet replacement products, all with the aim of reducing or eliminating the need for external insulin for people with T1D.
Researchers are searching for ways to use stem cells as a renewable source of insulin-producing cells which, when transplanted, would replace the beta cells that are destroyed in a person with T1D, allowing them to produce insulin again. This would lessen or eliminate the amount of external insulin required by someone living with T1D (either by injection, pen, or pump) for months or even decades.
The biggest challenges to stem cell replacement therapy include identifying the appropriate cell source (i.e., embryonic stem cells, induced pluripotent stem cells, porcine cells, etc.) and ensuring that they both function well and will not be rejected by the recipient’s immune system. Like transplanted organs, most stem cell-based islet replacement therapies require immunosuppressive medications to prevent rejection.
More progress on cell derived therapies for type 1 diabetes
PEC-Encap (VC-01™; see middle figure) was ViaCyte’s first product including a stem-cell derived precursor that once implanted in humans has demonstrated that they will mature into beta cells that produce insulin.
The company’s second technology, PEC Direct (VC-02™; see top figure), has now been the subject of two papers that report the preliminary results of its clinical study, which involved an international team of clinicians and researchers including several at the University of Alberta and at the University of British Columbia’s Faculty of Medicine and Vancouver Coastal Health (VCH).
The UBC-VCH study is part of larger international clinical trials led by ViaCyte, which is also studying the effectiveness of cell-replacement therapy on participants in sites across Canada, the U.S. and Belgium.
One of the new papers reports on 15 trial participants studied at the Vancouver site. At the start of the UBC-VCH study, each participant had several ViaCyte cell-containing devices implanted just below the skin. Each device, thin as a credit card, contained millions of lab-grown cells that originally came from a single stem cell line. These cells had been trained to mature into insulin-producing beta cells.
Six months after implantation, the cells had not only survived but successfully matured into insulin-producing beta cells, which helped the trial participants to sense blood sugar levels and release insulin when needed.
The insulin produced through the implanted cells was not enough for participants to forgo external insulin altogether, but the cells did survive and maintain function a full year post-transplantation. This demonstrates the potential for durability of this kind of cell replacement therapy, and may ideally prevent frequent implantation, which must be done surgically. Importantly, the trial did not reveal any safety concerns.
Next steps include determining what cells are optimal for transplantation, and the best transplantation site. There also needs to be further study on how long the cells work effectively, remain safe, whether a greater number of cells will enable long-term insulin production, and whether it is possible to eliminate immunosuppressive therapy.
This research was supported by funding from JDRF Canada, as well as Canada’s Stem Cell Network, Vancouver Coastal Health Research Institute, Canadian Institutes of Health Research, ViaCyte Inc. and California Institute for Regenerative Medicine.
These studies offer hope and cautious optimism about cell replacement therapy as a possible pathway to a T1D cure.
A third ViaCyte cell replacement product including a gene-edited stem cell source, VCTX210, developed in partnership with CRISPR Technologies, was recently approved for clinical trial by Health Canada. Unlike the PEC-Direct product used in the newly published results, this product would not require immunosuppression – a key next step on the beta cell replacement roadmap.
The ViaCyte clinical trials are one of several potential cell replacement cures therapies JDRF supports globally, as part of its overall research strategy.
Image taken from viacyte.com/pipeline/
