杭州瑞普晨创科技有限公司

Human pluripotent stem cell-derived islets for diabetes therapy

Challenges

Insulin injection and oral hypoglycemic drugs:
Unable to completely restore glycemic control, prone to development of irreversible complications eg: retinopathy, nephropathy, and peripheral neuropathy. A major burden of self-care.
Islet transplantation:
Scarcity of cadaveric donor islets, requires immunosuppression.
Solution

Leveraging human pluripotent stem cells (hPSCs) as an unlimited source of pancreatic
islet cells for clinical islet transplantation.

Realizing large-scale, standardized and industrialized production of pancreatic islet cells.

Independent intellectual property core technology

Human chemistry-induced pluripotent stem cell preparation

Limitations of existing technology

(1) Embryonic stem cell (ES cell) technology: can only be derived from early embryos, which has limitations and raises ethical controversies. (2) IPS cell technology: iPS cells can be obtained from adult autologous somatic cells, but a major risk of using them in humans is that the viruses used to generate iPS cells are associated with developing cancers. c-Myc, one of the genes used in the reprogramming process, poses another risk; its overexpression can trigger cancer development.
Solution

·The world's first-ever non-transgenic method for inducing human somatic cells into pluripotent stem cells (hCiPSCs) using small molecule compounds alone. ·Eliminating patent limitations at the seed cell level for the development of cell replacement therapy based on human pluripotent stem cells in China. （hCiPSC）

Differentiation Protocol

（hCiPSC）

Human chemistry-induced pluripotent stem cells (hCiPS cells) are obtained by inducing human adult cells with specific combinations of chemical small molecules. Compared to traditional methods, the technology of chemical small molecule-induced somatic cell reprogramming is simpler, more precise, and more controllable. As a non-integrative method, this technology avoids the safety issues caused by traditional transgenic operations, breaks through the limitations faced by previous iPS technologies, and has the potential to become a safer clinical treatment approach. Additionally, hCiPS cells provide high-quality seed sources for cell replacement therapy based on stem cells.

Optimized transplantation strategy

Limitations

infusion into the hepatic portal vein: 1. Engraftment challenges Instant blood-mediated inflammatory reaction (IBMIR) results in early graft loss, poor oxygen delivery, chronic hypoxia 2. Monitoring challenges Not conducive for imaging and biopsy 3. Surgical risks Bleeding and portal venous thrombosis
Solution

Reprogenix’s strategy: Injection beneath the abdominal anterior rectus sheath 1.Markedly improved survival and engraftment, circumvention of IBMIR* 2.Conducive microenvironment for functional maturation of SC-islets 3.SC-islet graft abundantly vascularized, with vessel density approaching that of native pancreatic islets 4.Regular, non-invasive monitoring of the graft is possible by medical imaging