Age-related macular degeneration (AMD) is the degeneration/dysregulation of cells of the retinal pigment epithelium (RPE) and is the most common cause of severe loss of central vision among people 50 and older, affecting approximately 200 million people worldwide [1]. While the molecular mechanisms of AMD remain unclear, risk factors for AMD include being 50 and older, smoking, having high blood pressure, and eating a diet high in saturated fat. Although there is no cure for AMD, cell therapies are being developed to halt or reverse disease progression with transplantation of healthy RPE cells to prevent loss and restore visual function. However, critical barriers to clinical translation of this promising therapy include the limited availability and expansion of healthy, functional, and immune compatible RPE cells derived from human pluripotent stem cells (hPSC).
AMD Cell Therapy
The safety and efficacy of hPSC-RPE cell transplantation in AMD patients are currently being tested in clinical trials. In most of these trials, hPSC-RPE cells are being generated by spontaneous differentiation to minimize the risk of patient exposure to xenogens. However, this method is labor intensive, inefficient, and highly variable across hPSC lines. An alternative is to use directed differentiation protocols which can significantly increase yields in hPSC-RPE cell production. Unfortunately, up until now, the most efficient protocols have remained incompatible with cell therapy due to the use of undefined animal products in the cell culture process, without which clinically relevant yields of hPSC-RPE cannot be achieved. Historically this has been one of the biggest stumbling blocks to the commercialization of therapeutic products using human stem cells. These delicate and highly complex cells require a support structure that mimics their natural environment in order to survive and thrive, but complex and poorly defined components in the manufacturing process are a serious impediment to FDA approval for the use of products in humans. You can read more about the problems in gaining FDA approval for therapeutic products using mixed extracellular matrix (ECM) gels or animal-derived products in our previous blog.
In a recent 2021 publication in the Journal of Stem Cell Research & Therapy [2], researchers at the Clem Jones Centre for Regenerative Medicine at Bond University in Australia described a robust protocol for the efficient production of RPE cells from human embryonic stem cells (hESCs) with high yield, a defined, single component extracellular matrix that is compatible with the FDA requirements for consistency and reproducibility in therapeutic products.
Manufacturing Clinical Grade Stem Cells with Vitronectin XF™
The goal of the study was to develop a rapid protocol to generate hESC-RPE cells at high efficiency using small molecules under feeder-free, xeno-free, and defined conditions. To design a protocol capable of generating the large numbers of homogeneous functional cells required for front-line clinical therapy that would enable hPSC technology to be used in the treatment of AMD over the coming decade.
“these data demonstrate the simple adaptation of hESC-RPE cell differentiation to xeno-free/defined conditions by changing the substrate from Matrigel to Vitronectin-XF”
Limnios et all, 2021
At the core of the new protocol was the replacement of the non-defined, mixed ECM gel and other animal derived products with a consistent and well characterized alternative. The authors selected Vitronectin XF from Nucleus Biologics as a xeno-free, recombinant ECM that is human derived and fully glycosylated. In a series of experiments, the researchers were able to demonstrate that the efficiency of their revised protocol was consistently high and reproducible. In testing across multiple cell lines, the authors were able to demonstrate fast and efficient cell differentiation using Vitronectin XF in a timeframe far shorter than other previously published studies.
The publication marks another important step forward in the reduction of cell and regenerative medicine research to clinical practice. The successful application of hESC technology to the treatment of AMD holds the promise of a significantly improved quality of life for patients, enabling those suffering with a significant visual impairment to see again. Nucleus Biologics is proud to be a part of the effort to make these advanced regenerative therapies a clinical reality.
Learn more about Vitronectin XF on our website
References:
- Wong W, Su X, Li X, Cheung CG, Klein R, Cheng C-Y, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2(2):e106–16. https://doi.org/10.1016/S2214-109X(13)70145-1.
- Limnios, I.J., Chau, YQ., Skabo, S.J. et al. Efficient differentiation of human embryonic stem cells to retinal pigment epithelium under defined conditions. Stem Cell Res Ther 12, 248 (2021). https://doi.org/10.1186/s13287-021-02316-7.
