Bring back light to people whose world has gone dark
Engineered cell therapy targeting neuroprotective pathways to treat retinal degeneration





Prevailing Challenges
Retinal degeneration, like many other complex diseases, involves progressive failures in multiple systems. Standard approaches targeting one single pathway has historically failed to work. A more sophisticated approach targeting multiple pathways is thus required.
The use of stem cells and their secretome for neuroprotection has emerged as novel therapeutic approach over the last decade. However, their success in the clinic has proved limited. In particular, stem cell therapies are confronted with two obstacles

Undetermined cell fate leading to cell differentiation towards a heterogeneous cell population and uncontrolled cell-cell interactions
- Ganglion cell
- Amacrine cell
- Bipolar cell
- Müller cell
- Horizontal cell
- Rod photoreceptor
- Cone photoreceptor


Unpredictable in-vivo microenviroment leading to unwanted cell-matrix interaction













Our Science
Cellular Development Platform
At InGel our scientists have discovered a novel cell state, during the cell differentiation process, for the retinal neurons including rods, cones and the ganglion cells. In this state, the cells are fated to only differentiate towards one cell type, therefore achieving high purity, but and the same time are still proliferative and can be expanded to hundred of millions. We named them Precursor Cells.
Unlike multi-potent stem cells that may differentiate towards many cell types, these precursor cells make great therapeutic candidates because they do not encounter the unwanted behaviors from a heterogeneous cell population and messy cell-cell interactions. We can also conduct elegant target engagement studies by isolating the pure cells’ secretome and identify the mechanism of neuroprotection.

- Fetal derived
- Confirmed phenotype, morphology
- High purity (>95%)
- Highly neuroprotective

- Fetal derived
- Confirmed phenotype, morphology
- High purity (>98%)
- High engraftment

- ESc derived
- Confirmed phenotype, morphology
- High purity from human, mouse and pig sources
Hydrogel Delivery Platform
The other problem confronting regenerative cell therapy is its delivery in vivo. Many studies have shown that the cellular response varies greatly depending on its microenvironment. Mechanical cues such as the injection shear stress alone will trigger apoptosis. Other factors, such as spatial cues (cell anchorage), chemical cues (healthy vs diseased host tissue environment) also trigger different cell behavior in vivo.
That is why the other key innovation at InGel is the engineering of a biomimetic hydrogel matrix, enabling the in vivo delivery of the retinal neurons. Our material scientists took inspiration from the human eye and engineered a hydrogel that mimics the human vitreous, consisting of only Hyaluronic acid and Gelatin. This elegant and simple design allows for both intravitreal and subretinal injections and can be tuned to exhibit different stiffness and degradation timeline.


Last, because the matrix is engineered to mimic the human vitreous, the degradation of the hydrogel follows an enzymatic degradation, via collagenase and hyaluronidase already present in the eye. This offers a promising safety profile as the metabolites are constantly being cleared by the human eye.
Disease
We are focused on complex retinal degenerative diseases with high unmet need.
Research Platform
RegenesisTM is a target discovery and validation platform for neuroprotective pathways in the eye. It leverages single cell proteomics profiling for rod photoreceptors and their secretome. By modifying specific gene or gene combo in the pure human rod photoreceptor, InGel is able to isolate protein of neuroprotective significance first in vitro and later in vivo. The in vitro testing stage is high-throughput, as testing can be performed in pure human cone photoreceptor population.
Our Team
Leadership Team



Scientific & Clinical Advisory Board




Our Publications
A bioinspired gelatin-hyaluronic acid-based hybrid interpenetrating network for the...
https://www.nature.com/articles/s41536-021-00195-3Injectable gelatin hydroxyphenyl propionic acid hydrogel protects human retinal progenitor...
https://www.sciencedirect.com/science/article/abs/pii/S2352940720300494The effect of injectable gelatin-hydroxyphenylpropionic acid hydrogel...
https://www.sciencedirect.com/science/article/abs/pii/S0142961212000695?Controlling Growth Factor Diffusion by Modulating Water Content in Injectable...
https://www.liebertpub.com/doi/full/10.1089/ten.tea.2020.03133D hydrogels protect human retinal progenitor cells from stress exerted during transplantation
https://iovs.arvojournals.org/article.aspx?articleid=2746936In Situ Cross-linking Hydrogel as a Vehicle for Retinal Progenitor Cell Transplantation
https://journals.sagepub.com/doi/full/10.1177/0963689719825614Do get in touch
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